Impact of a 22q11.2 Microdeletion on Adult All-Cause Mortality in Tetralogy of Fallot Patients

BackgroundBecause of the importance of identifying factors that affect late outcomes in the increasing population of those with tetralogy of Fallot (TOF), we aimed to determine the effect of a 22q11.2 microdeletion on adult mortality, while accounting for pulmonary atresia, known to be enriched in 22q11.2 deletion syndrome (22q11.2DS).MethodsWe studied 612 individuals with TOF recruited as adults at a single centre, 80 (13.1%) with molecularly confirmed 22q11.2 deletions and 532 without 22q11.2DS, followed for a total of 5961.3 person-years. Using a case-control design, Cox proportional hazard regression and Kaplan-Meier curves, we evaluated the effect of a 22q11.2 deletion on mortality and survival.ResultsAll-cause mortality was 1.87% per person-year in the 22q11.2DS-TOF group and 0.80% in the other-TOF group. The presence of a 22q11.2 microdeletion was a significant predictor of adult mortality in TOF (hazard ratio, 5.00; P < 0.0001), after accounting for pulmonary atresia (hazard ratio, 2.71; P = 0.0106) and other factors. Overall, individuals with 22q11.2DS died on average 17.7 years earlier (P = 0.0055) than others with TOF, predominantly of cardiovascular causes, with proportionately more sudden cardiac deaths in those with 22q11.2DS-TOF (n = 5 [38.5%] vs n = 5 [11.9%], other-TOF; P = 0.0447). Kaplan-Meier curves showed reduced survival for those with 22q11.2DS (P < 0.0001); probability of survival to age 45 years, without pulmonary atresia, was 72% (22q11.2DS-TOF) and 98% (other-TOF).ConclusionsThe results suggest that the 22q11.2 deletion significantly contributes to premature mortality in adults with TOF, mediated only in part by greater anatomic complexity. The interpretation of late outcome data in TOF will likely benefit from further genetic subtyping.     

The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis

Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).

Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.

Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?r²: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.

Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD.     

Fibrinogen levels are associated with bleeding in patients with primary immune thrombocytopenia

Abstract

Bleeding is the most common clinical symptom and the leading cause of death in patients with primary immune thrombocytopenia (ITP). Our research intends to verify the role of fibrinogen levels as independent determinants of bleeding. We retrospectively analyzed the relationship between fibrinogen levels and bleeding events in 463 patients. Additionally, we confirmed the impact of fibrinogen level on clot firmness in 25 patients via thrombelastography (TEG). Fibrinogen levels (median and inter-quartile range, IQR) were significantly different (p < .001) between bleeding and non-bleeding patients [258(207–314) mg/dL vs. 315(262–407) mg/dL, respectively]. Further analyzes in three subgroups based on platelet (PLT) count showed that non-bleeding patients still had higher fibrinogen levels than bleeding patients. The optimal discriminant threshold of fibrinogen in bleeding was 288.5 mg/dL according to receiver operating characteristic (ROC) curves. Patients were divided into low (LF, 230[193–258] mg/dL) and high (HF, 349[313–424] mg/dL) fibrinogen groups based on this threshold. Bleeding event rates were significantly different (LF: 84.6% vs. HF: 60.4%, P < .001) between the two groups. Multivariable analyses further confirmed these differences. Moreover, TEG parameters showed elevated clot firmness in the HF group. Our data suggest that high fibrinogen levels are associated with reduced bleeding events.     

Differential lipid metabolism outcomes associated with ADRB2 gene polymorphisms in response to two dietary interventions in overweight/obese subjects

Background and aims

A precise nutrigenetic management of hypercholesterolemia involves the understanding of the interactions between the individual's genotype and dietary intake. The aim of this study was to analyze the response to two dietary energy-restricted interventions on cholesterol changes in carriers of two ADRB2 polymorphisms.

Serum calcium levels independently predict in-hospital mortality in patients with acute myocardial infarction

Background and aim

Serum calcium levels (sCa) were reported to be associated with cardiovascular risk factors, incidence of coronary artery disease and acute myocardial infarction (AMI). The current study evaluated the association between sCa and in-hospital mortality among AMI patients.

Efficacy and Safety of the PCSK9 Inhibitor Evolocumab in Patients with Mixed Hyperlipidemia

Purpose

Evolocumab significantly reduces low-density lipoprotein-cholesterol (LDL-C); we investigated its effects on LDL-C lowering in patients with mixed hyperlipidemia.

Methods

We compared the efficacy and safety of evolocumab in hypercholesterolemic patients selected from the phase 2 and 3 trials who had fasting triglyceride levels ≥1.7 mmol/L (150 mg/dL elevated triglycerides) and <1.7 mmol/L (without elevated triglycerides). Fasting triglyceride level ≥ 4.5 mmol/L at screening was an exclusion criterion for these studies, but post-enrollment triglyceride levels may have exceeded 4.5 mmol/L (400 mg/dL). Efficacy was evaluated in four phase 3 randomized studies (n = 1148) and safety from the phase 2 and 3 studies (n = 2246) and their open-label extension studies (n = 1698). Efficacy analyses were based on 12-week studies, while safety analyses included data from all available studies. Treatment differences were calculated vs. placebo and ezetimibe after pooling dose frequencies.

Results

Mean treatment difference in percentage change from baseline in LDL-C for participants with elevated triglycerides and those without elevated triglycerides (mean of weeks 10 and 12) with evolocumab was approximately ?67 % vs. placebo and ?42 % vs. ezetimibe (all P < 0.001) compared to ?6 % vs. placebo and ?39 % vs. ezetimibe, respectively. Treatment differences for evolocumab vs. placebo and ezetimibe followed a similar pattern for non–high-density lipoprotein (HDL-C) and apolipoprotein B. Evolocumab was well tolerated, with balanced rates of adverse events leading to discontinuation of evolocumab vs. comparator (placebo and/or ezetimibe).

Conclusion

The significant reductions of atherogenic lipids including LDL-C, non–HDL-C, and apolipoprotein B seen with evolocumab are similar in patients with and without mixed hyperlipidemia.

     

Oxidative stress markers in coronary artery disease patients with diabetes mellitus

Coronary artery disease (CAD) is the major cause of morbidity and mortality. Diabetes is one of the powerful and independent risk factor for CAD. Hyperglycemia and hypercholesterolemia initiate the oxidative stress and complications like atherosclerosis which induces poor prognosis in diabetic CAD patients. The aim of the present study was to assess oxidative stress by comparing the levels of malondialdehyde and comet tail length in diabetic CAD patients, non-diabetic CAD patients and healthy controls. The study included 400 subjects of which 200 were healthy controls, 100 were diabetic CAD patients, and 100 were non-diabetic CAD patients. Fasting and postprandial glucose levels, glycosylated hemoglobin, serum lipid levels, malondialdehyde, and DNA damage were estimated in all subjects by using commercially available kits and standard protocols. FBS (185.60 ± 6.0 mg/dL), PPG (250 ± 7.06 mg/dL), HbA1c (10.65 ± 2.01 %), TC (280.72 ± 5.25 mg/dL), TG (195.11 ± 5.99 mg/dL), LDL (163.28 ± 5.68 mg/dL), MDA (9.74 ± 2.33 n moles/mL), and comet tail length (21.60 ± 5.69 μm) were significantly high in diabetic CAD patients (p < 0.05) compared to non-diabetic CAD patients and controls. Fasting and postprandial blood sugar levels significantly correlated with oxidative stress markers like MDA (r = 0.553, r = 0.557, p < 0.01) and comet tail length (r = 0.489, r = 0.626, p < 0.01) in diabetic CAD patients compared to non-diabetic CAD patients. Our study showed that diabetic CAD patients with increased levels of oxidative stress markers (MDA and DNA damage) might have the poor prognosis than non-diabetic CAD patients.     

Complex congenital heart disease in unaffected relatives of adults with 22q11.2 deletion syndrome

The 22.q11.2 deletion syndrome (22q11DS) is a common genetic condition associated with 22q11.2 microdeletions and classically has included congenital heart disease (CHD) as a part of the variable expression. Some evidence has shown that relatives of those with 22q11DS might be at an increased risk of CHD in the absence of 22q11.2 deletions. We obtained a detailed family history of CHD in the first- to third-degree relatives (n = 2,639) of 104 adult probands with 22q11DS. We compared the prevalence of CHD in the relatives without 22q11.2 deletions to the published general population prevalence. We also investigated the effect of CHD in the probands on prevalence of CHD in the relatives. Of the 104 probands with 22q11DS, 14 (13.5%) had 17 relatives (17 of 2,639, 0.6%) with CHD. Of 66 probands with CHD, 15 (0.9%) of their 1,663 relatives had CHD, a significantly greater prevalence than that for the relatives of probands without CHD (0.2%, 2 of 976, p = 0.041, odds ratio 4.43, 95% confidence interval 1.03 to 40.00). In relatives of probands with CHD, the prevalence of those with severe CHD (0.36%) was significantly elevated compared to population expectations (0.061%, p = 0.007, odds ratio 5.88, 95% confidence interval 2.16 to 12.85). In conclusion, these results support a heritable susceptibility to CHD in families of probands with 22q11DS, in addition to that imparted by microdeletion 22q11.2. The occurrence of CHD in relatives might be related to the expression of CHD in the proband with 22q11DS. These findings have potential implications for the genetic counseling of families of those with 22q11DS and support the notion that interacting genetic variants might contribute to the variable expression of 22q11DS.     

Evaluation of the effects of glucose on osmolal gap using freezing point depression and vapor pressure methods

The measurement of serum osmolality, and the calculation of osmolal gap (OG) from a calculated osmolality are widely used in clinical and emergency medicine. In this study, the possible effects of blood glucose on OG were investigated by freezing point depression and vapor pressure methods. The concentrations of sodium, glucose, blood urea nitrogen and osmolalities of 2640 samples were measured. There were two methods for calculating serum osmolality: freezing point depression method (n = 2399) and vapor pressure method (n = 241). The OG was positively associated with glucose in glucose 110–450 mg/dL (r = 0.191, p < 0.001) and glucose > 450 mg/dL (r = 0.372, p < 0.001), but not in glucose < 110 mg/dL (r = 0.017, p = 0.711) in freezing point depression method. However, OG had no correlation with glucose regardless of glucose level in vapor pressure method. In freezing point depression method, compared with the groups of glucose <110 and 110–450 mg/dL, the group with glucose >450 mg/dL had higher OG (p < 0.001) and higher prevalence of OG > 10 mOsm/Kg H₂O (p < 0.001). Our study demonstrated that OG is impacted by increasing blood glucose concentration using freezing point depression method, special attention should be made to blood glucose concentrations when using freezing point depression method to determine OG.     

Congenital Heart Disease as a Warning Sign for the Diagnosis of the 22q11.2 Deletion

Background

To alert for the diagnosis of the 22q11.2 deletion syndrome (22q11.2DS) in patients with congenital heart disease (CHD).

Objective

To describe the main CHDs, as well as phenotypic, metabolic and immunological findings in a series of 60 patients diagnosed with 22q11.2DS.

Methods

The study included 60 patients with 22q11.2DS evaluated between 2007 and 2013 (M:F=1.3, age range 14 days to 20 years and 3 months) at a pediatric reference center for primary immunodeficiencies. The diagnosis was established by detection of the 22q11.2 microdeletion using FISH (n = 18) and/or MLPA (n = 42), in association with clinical and laboratory information. Associated CHDs, progression of phenotypic facial features, hypocalcemia and immunological changes were analyzed.

Results

CHDs were detected in 77% of the patients and the most frequent type was tetralogy of Fallot (38.3%). Surgical correction of CHD was performed in 34 patients. Craniofacial dysmorphisms were detected in 41 patients: elongated face (60%) and/or elongated nose (53.3%), narrow palpebral fissure (50%), dysplastic, overfolded ears (48.3%), thin lips (41.6%), elongated fingers (38.3%) and short stature (36.6%). Hypocalcemia was detected in 64.2% and decreased parathyroid hormone (PTH) level in 25.9%. Decrease in total lymphocytes, CD4 and CD8 counts were present in 40%, 53.3% and 33.3%, respectively. Hypogammaglobulinemia was detected in one patient and decreased concentrations of immunoglobulin M (IgM) in two other patients.

Conclusion

Suspicion for 22q11.2DS should be raised in all patients with CHD associated with hypocalcemia and/or facial dysmorphisms, considering that many of these changes may evolve with age. The 22q11.2 microdeletion should be confirmed by molecular testing in all patients.     

Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome

Interneurons are thought to be a primary pathogenic target for several behavioral disorders that arise during development, including schizophrenia and autism. It is not known, however, whether genetic lesions associated with these diseases disrupt established molecular mechanisms of interneuron development. We found that diminished 22q11.2 gene dosage—the primary genetic lesion in 22q11.2 deletion syndrome (22q11.2 DS)—specifically compromises the distribution of early-generated parvalbumin-expressing interneurons in the Large Deletion (LgDel) 22q11.2DS mouse model. This change reflects cell-autonomous disruption of interneuron migration caused by altered expression of the cytokine C-X-C chemokine receptor type 4 (Cxcr4), an established regulator of this process. Cxcr4 is specifically reduced in LgDel migrating interneurons, and genetic analysis confirms that diminished Cxcr4 alters interneuron migration in LgDel mice. Thus, diminished 22q11.2 gene dosage disrupts cortical circuit development by modifying a critical molecular signaling pathway via Cxcr4 that regulates cortical interneuron migration and placement.Behavioral and psychiatric diseases, including autism and schizophrenia, are considered disorders of cortical circuitry (1–3). Despite variable onset and severity, the available evidence suggests that aberrant neural development leads to inappropriate circuit formation in these disorders. Cortical interneurons—essential regulators of cortical activity and synchrony for complex functions such as social interaction, learning, and memory (4)—are thought to be primary targets for this developmental pathogenesis (5–7). Indeed, the most consistent observations in postmortem cortex from patients with schizophrenia include altered interneuron number, distribution, or gene expression (8, 9). These studies cannot resolve whether such changes reflect developmental causes or pathologic consequences of cortical circuit dysfunction. Moreover, it is not clear whether pathogenic processes that lead to these disorders disrupt established or novel mechanisms that regulate interneuron development. Thus, we determined whether key cellular mechanisms and molecular pathways known to regulate interneuron differentiation are disrupted in the LgDel mouse model (10) of 22q11.2 deletion syndrome (22q11.2DS), a genetic syndrome highly associated with cortical circuit disorders.The microdeletion at chromosome 22q11.2 that gives rise to 22q11.2DS is one of the most significant genetic risks for cortical circuit disorders (11–13). Postmortem studies of the cerebral cortex from 22q11.2DS patients implicate abnormal neuronal migration (14); imaging demonstrates related cortical anomalies including polymicrogyria and region-selective gray matter thinning (15, 16); and magnetic resonance spectroscopic studies show reduced GABA function (17). Thus, in 22q11.2DS, the available evidence indicates that cortical circuits are compromised and GABAergic interneurons are altered. We now report in the LgDel mouse—in which recent studies (18–20) suggest that cortical circuit assembly and function is compromised—a mechanistic relationship between diminished 22q11.2 dosage and a key molecular pathway that regulates interneuron migration during cortical development. LgDel interneuron phenotypes reflect interneuron-specific disruption of cytokine receptor Cxcr4, which has been shown to influence placement, migratory trajectory, and motility of these cells during cortical development (21–25). Thus, we define a relationship between 22q11.2DS, a compelling example of a copy number variant (CNV) syndrome thought to cause cortical circuit disorders, and Cxcr4-mediated signaling, an established mechanism that ensures normal cortical interneuron development.     

Cigarette smoking reduces platelet reactivity independently of clopidogrel treatment in patients with non-ST elevation acute coronary syndromes

Smokers receiving clopidogrel show a lower residual platelet reactivity than non-smokers, a phenomenon generally ascribed to smoking-induced increased production of clopidogrel active metabolite, but also associated with the high hemoglobin levels of smokers, which decreases platelet reactivity in tests that measure platelet function in whole blood. We evaluated the impact of cigarette smoking and of hemoglobin levels on platelet reactivity index (PRI) measured by the vasodilator-stimulated phosphoprotein phosphorylation (VASP-P) assay in whole blood samples from patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary interventions, both before and after clopidogrel administration.

PRI was measured in 718 clopidogrel-naïve NSTE-ACS patients, both before and 1 month after treatment with clopidogrel (75 mg daily). Smokers (n = 347, 48%) had significantly lower mean PRI levels at both baseline (57.7 ± 24.1 vs. 64.8 ± 19.8, p < 0.001) and 1 month (43.4 ± 20.3% vs. 46.8 ± 18.0%, p = 0.017) than non-smokers. After adjusting for potential confounders (age, sex, diabetes, chronic kidney disease, Syntax score>15), the β coefficient of smoke on PRI was ?8.51 [?11.90 to ?5.11, p < 0.001] at baseline and ?3.41 [?6.30 to ?0.51, p = 0.02] after 1 month. Hemoglobin was higher in smokers (13.8 ± 1.5 g/dL) than non-smokers (13.1 ± 1.7 g/dL, p < 0.001), but was not significantly correlated with PRI both at baseline (Rho = 0.02, p = 0.60) and at 1 month (Rho = 0.01, p = 0.80).

Our analysis confirms that clopidogrel-treated smokers have lower platelet reactivity, measured by the VASP-P assay, compared to clopidogrel-treated non-smokers. However, smokers had lower platelet reactivity already before receiving clopidogrel treatment, suggesting that smoke affects platelet reactivity independently of its potential effect on the pharmacokinetics of clopidogrel. Our data also indicate that such an effect is not mediated by increased hemoglobin levels.     

Aspirin intake in the morning is associated with suboptimal platelet inhibition,as measured by serum Thromboxane B2, during infarct-prone early-morning hours

Aspirin is traditionally taken once daily in the morning and considered to be effective throughout the 24h interval. Cardiovascular events occur most frequently in the early morning, suggesting that these hours are critical in terms of adequate platelet inhibition. This study therefore assed platelet function in the early morning—8.00 AM—in healthy volunteers, during a once-daily (OD) 80 mg morning in comparison with an OD evening regimen and a twice-daily (BID) 40 mg regimen. It was an open-label randomized cross-over study, comprising 12 healthy subjects. Subjects were allocated to three sequential dosage regimens: 80 mg OD at 8.00 AM, 80mg OD at 8.00 PM, and 40 mg BID at 8.00 AM and PM. Platelet function 12 and 24 hours after aspirin intake was measured by means of serum thromboxane B₂ (sTxB₂) levels, the collagen/epinephrine closure time (Platelet Function Analyzer(PFA)-200^®) and the Aspirin Reaction Units (ARU, VerifyNow^®). The results demonstrated that early morning sTxB₂ concentrations were 5843pg in the morning regimen, 2877pg in the evening OD regimen, and 3343pg in the BID regimen (morning- vs evening regimen p = < 0.01; morning- vs BID regimen p = < 0.01). Early morning PFA-closure time (p = 0.12)) as well as VerifyNow ARU (p = 0.17) mean values were similar for all three regimens. In conclusion, the OD-morning regimen seems to acquire the lowest level of platelet inhibition during the critical early morning window. Switching to an OD-evening or BID intake seems prudent, although further research on clinical cardiovascular outcome in patients with stable cardiovascular disease is needed.     

Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome

The 22q11 deletion (or DiGeorge) syndrome (22q11DS), the result of a 1.5- to 3-megabase hemizygous deletion on human chromosome 22, results in dramatically increased susceptibility for “diseases of cortical connectivity” thought to arise during development, including schizophrenia and autism. We show that diminished dosage of the genes deleted in the 1.5-megabase 22q11 minimal critical deleted region in a mouse model of 22q11DS specifically compromises neurogenesis and subsequent differentiation in the cerebral cortex. Proliferation of basal, but not apical, progenitors is disrupted, and subsequently, the frequency of layer 2/3, but not layer 5/6, projection neurons is altered. This change is paralleled by aberrant distribution of parvalbumin-labeled interneurons in upper and lower cortical layers. Deletion of Tbx1 or Prodh (22q11 genes independently associated with 22q11DS phenotypes) does not similarly disrupt basal progenitors. However, expression analysis implicates additional 22q11 genes that are selectively expressed in cortical precursors. Thus, diminished 22q11 gene dosage disrupts cortical neurogenesis and interneuron migration. Such developmental disruption may alter cortical circuitry and establish vulnerability for developmental disorders, including schizophrenia and autism.     

Intravenous Albumin Shortens the Duration of Hospitalization for Patients with Hypoalbuminemia and Bleeding Peptic Ulcers: A Pilot Study

Background

Patients with hypoalbuminemia have an increased risk of ulcer rebleeding and longer length of hospitalization.

Aims

This study aimed to test whether intravenous albumin can decrease the incidence of rebleeding or shorten the duration of hospitalization in patients with bleeding peptic ulcers and hypoalbuminemia.

Methods

Sixty-two patients with bleeding peptic ulcers and Rockall scores ≥6 were prospectively enrolled after having received endoscopic therapy. The enrolled patients were divided into a normal albumin group (serum albumin ≥3 g/dL, n = 39) or an intervention group (<3 g/dL, n = 23) to receive a 3-day course of omeprazole infusion and 25-day oral esomeprazole. Patients (n = 29) with bleeding ulcers and hypoalbuminemia who received the same dose of intravenous and oral omeprazole but did not receive albumin therapy were enrolled from a previous study as the control group. In the intervention group, patients received albumin infusion (10 g q8h) for 1 day (serum albumin levels 2.5–2.9 g/dL) and 2 days (<2.5 g/dL), respectively.

Results

The 28-day cumulative rebleeding rates were similar between the intervention group and the control group (39.1 vs. 42.3 %, p = 0.99). The intervention group had a shorter duration of hospitalization (9 vs. 15 days, p = 0.02) than cohort controls. The risk of rebleeding developed after discharge were similar (normal albumin group vs. intervention group vs. control group, 1/5 [20 %] vs. 2/9 [22.2 %] vs. 1/11 [9.1 %], p = 0.7).

Conclusions

Albumin administration shortens the duration of hospitalization for patients with peptic ulcer bleeding and hypoalbuminemia, but does not decrease the incidence of rebleeding.     

Revised GH and cortisol cut-points for the glucagon stimulation test in the evaluation of GH and hypothalamic–pituitary–adrenal axes in adults: results from a prospective randomized multicenter study

Context

Recent studies suggest using lower GH cut-points for the glucagon stimulation test (GST) in diagnosing adult GH deficiency (GHD), especially in obese patients. There are limited data on evaluating GH and hypothalamic–pituitary–adrenal (HPA) axes using weight-based dosing for the GST.

Objective

To define GH and cortisol cut-points to diagnose adult GHD and secondary adrenal insufficiency (SAI) using the GST, and to compare fixed-dose (FD: 1 or 1.5 mg in patients >90 kg) with weight-based dosing (WB: 0.03 mg/kg). Response to the insulin tolerance test (ITT) was considered the gold standard, using GH and cortisol cut-points of ≥3 ng/ml and ≥18 µg/dL, respectively.

Design

28 Patients with hypothalamic-pituitary disease and 1–2 (n = 14) or ≥3 (n = 14) pituitary hormone deficiencies, and 14 control subjects matched for age, sex, estrogen status and body mass index (BMI) underwent the ITT, FD- and WB-GST in random order.

Results

Age, sex ratio and BMI were comparable between the three groups. The best GH cut-point for diagnosis of GHD was 1.0 (92 % sensitivity, 100 % specificity) and 2.0 ng/mL (96 % sensitivity and 100 % specificity) for FD- and WB-GST, respectively. Age negatively correlated with peak GH during FD-GST (r = ?0.32, P = 0.04), but not WB-GST. The best cortisol cut-point for diagnosis of SAI was 8.8 µg/dL (92 % sensitivity, 100 % specificity) and 11.2 µg/dL (92 % sensitivity and 100 % specificity) for FD-GST and WB-GST, respectively. Nausea was the most common side effect, and one patient had a seizure during the FD-GST.

Conclusion

The GST correctly classified GHD using GH cut-points of 1 ng/ml for FD-GST and 2 ng/ml for WB-GST, hence using 3 ng/ml as the GH cut-point will misclassify some GH-sufficient adults. The GST may also be an acceptable alternative to the ITT for evaluating the HPA axis utilizing cortisol cut-points of 9 µg/dL for FD-GST and 11 µg/dL for WB-GST.

     

Low Albumin Levels Are Associated with Mortality Risk in Hospitalized Patients

Background

The aim of this study was to investigate the association of albumin levels on admission and change in levels during hospitalization with hospitalization outcomes.

Clinical experience in using CD20 monoclonal antibody in treating severe systemic lupus erythematosus

Background and method: This clinical experience involved the treatment of resistant systemic lupus erythematosus (SLE) patients with CD20 monoclonal antibody. Five patients failed conventional therapy, two developed complications and one needed rituximab as an emergency measure. Four patients had lupus nephritis, three had autoimmune hemolytic anemia, two had immune thrombocytopenia and one had lupoid hepatitis. The patients were aged 14–49 years, (mean 28.63). Three were Malays, two Chinese, two Indian and one Turkish; six were females. Mean disease duration was 63.25 months and mean total rituximab dose received was 2812.50 mL. Results: Hemoglobin levels improved from 9.3 ± 5.7 to 13.1 ± 8.6 g/dL for two SLE patients with autoimmune hemolytic anemia after 34 weeks (P = 0.180). Platelet counts improved from 25 ± 17 to 198 ± 97 × 10⁹/high powered field from 0 to 10 weeks for three SLE patients with immune thrombocytopenia (P = 0.109). In the lupus nephritis patients on rituximab, serum albumin improved from 24.5 ± 23.2 to 37.5 ± 31.8 mmol/L (n = 3) from week 0 to week 17 (P = 0.100). Urine protein creatinine ratio improved from 0.55 ± 0.23 to 0.08 ± 0.03 g/mmol creatinine (P = 0.068) from week 0 to week 13. C3 and C4 improved from 90.8 ± 36.5 to 120.7 ± 37.9 (P = 0.07) and 21.6 ± 10.1–27.3 ± 16.2 mg/dL (P = 0.27), respectively, and Systemic Lupus Erythematosus Activity Disease Index was reduced from 17.9 ± 11.2 to 6.3 ± 6.8 (P = 0.375) after 8 weeks. Two patients developed drug reactions to rituximab. Conclusion: All of the patients responded to rituximab on top of their conventional therapy.