Low-Dose Otelixizumab Anti-CD3 Monoclonal Antibody DEFEND-1 Study: Results of the Randomized Phase III Study in Recent-Onset Human Type 1 Diabetes

OBJECTIVE

Previous studies demonstrated that the anti-CD3 monoclonal antibody otelixizumab, administered at a total dose of 48–64 mg, can slow the loss of C-peptide in recent-onset type 1 diabetes patients, with frequent reactivation of Epstein Barr virus (EBV). The DEFEND-1 (Durable Response Therapy Evaluation for Early or New-Onset Type 1 Diabetes) trial was designed to test whether a lower dose of otelixizumab could preserve C-peptide secretion in new-onset type 1 diabetes patients.

RESEARCH DESIGN AND METHODS

A multicenter, randomized, placebo-controlled trial was performed in sites in the U.S., Canada, and Europe. Two hundred eighty-one patients were randomized to treatment with 3.1 mg otelixizumab administered over 8 days or placebo. The primary end point of the study was the change in C-peptide area under the curve (AUC) from a 2-h mixed-meal tolerance test at month 12.

RESULTS

The change in 2-h C-peptide AUC was not different between placebo-treated patients and otelixizumab-treated patients (−0.20 vs. −0.22 nmol/L, P = 0.81). Secondary end points, including HbA_1c, glucose variability, and insulin dose, were also not statistically different between the two groups. More patients in the otelixizumab group than in the placebo group experienced adverse events, mostly grade 1 or grade 2. There was no EBV reactivation (viral load >10,000 copies/10⁶ peripheral blood mononuclear cells) in the otelixizumab group, in contrast with previously published studies at higher doses of otelixizumab.

CONCLUSIONS

Otelixizumab was well tolerated in patients with recent-onset type 1 diabetes at a total dose of 3.1 mg, but did not achieve preservation of levels of C-peptide or other markers of metabolic control.     

Preliminary Results of Cord Blood Mononuclear Cell Therapy for Multiple System Atrophy: A Report of Three Cases

Objectives

This study was designed to evaluate the effects of cord blood mononuclear cell transplantation in multiple system atrophy (MSA).

Clinical Presentation and Intervention

Cord blood mononuclear cells (1-2 × 10⁸ cells/6 ml) were injected into the subarachnoid space using lumbar puncture in patients 1 and 2 and cisterna magna puncture in patient 3 in the 3 patients with MSA. The cord blood mononuclear cell transplantation was repeated 30 days after the first treatment in patients 1 and 2; it was repeated twice in patient 3. The clinical outcomes of treatment were used to assess the Unified Multiple System Atrophy Rating Scale (UMSARS) before, 90 and 180 days after the cell transplantation. There were no clinically noticeable side effects from the cord blood mononuclear cells. The UMSARS scores improved after 90 days of the cord blood mononuclear cell therapy in all 3 patients, the most significant improvement being that in urinary incontinence and ability to walk.

Conclusions

Cord blood mononuclear cell transplantation was safe and potentially effective in the treatment of MSA in the 3 patients.Key Words: Cord blood mononuclear cell, Transplantation, Multiple system atrophy     

Adoption of the chronic care model to improve HIV care: In a marginalized,largely aboriginal population

Objective

To measure the effectiveness of implementing the chronic care model (CCM) in improving HIV clinical outcomes.

Design

Multisite, prospective, interventional cohort study.

Setting

Two urban community health centres in Vancouver and Prince George, BC.

Participants

Two hundred sixty-nine HIV-positive patients (18 years of age or older) who received primary care at either of the study sites.

Intervention

Systematic implementation of the CCM during an 18-month period.

Main outcome measures

Documented pneumococcal vaccination, documented syphilis screening, documented tuberculosis screening, antiretroviral treatment (ART) status, ART status with undetectable viral load, CD4 cell count of less than 200 cells/mL, and CD4 cell count of less than 200 cells/mL while not taking ART compared during a 36-month period.

Results

Overall, 35% of participants were women and 59% were aboriginal persons. The mean age was 45 years and most participants had a history of injection drug use that was the presumed route of HIV transmission. During the study follow-up period, 39 people died, and 11 transferred to alternate care providers. Compared with their baseline clinical status, study participants showed statistically significant (P < .001 for all) increases in pneumococcal immunization (54% vs 84%), syphilis screening (56% vs 91%), tuberculosis screening (23% vs 38%), and antiretroviral uptake (47% vs 77%), as well as increased viral load suppression rates among those receiving ART (72% vs 90%). Stable housing at baseline was associated with a 4-fold increased probability of survival. Aboriginal ethnicity was not associated with better or worse outcomes at baseline or at follow-up.

Conclusion

Application of the CCM approach to HIV care in a marginalized, largely aboriginal patient population led to improved disease screening, immunization, ART uptake, and virologic suppression rates. In addition to addressing underlying social determinants of health, a paradigm shift away from an “infectious disease” approach to a “chronic disease management” approach to HIV care for marginalized populations is strongly recommended.     

Cord Blood Banking and Transplantation in China: A Ten Years Experience of a Single Public Bank

Background

Umbilical cord blood (UCB) has successfully used for transplantation to treat hematologic malignancies and genetic diseases. Herein, we describe the experience generated in a single public UCB bank at Zhejiang Province in China.

Methods

Good manufacturing practice and standard operating procedures were used to address donor selection as well as UCB collection, processing, and cryopreservation. Total nucleated cells (TNCs), cellular viability, CD34+ cells, and colony-forming units were determined, and infectious diseases screening test, sterility test, and HLA typing for UCB units were done.

Results

Only 18.51% of all collected UCB units met storage criteria, and 7,056 UCB units were cryopreserved in 10 years. The volume of UCB units was 95.0 ± 22.0 ml. The number of TNCs before and after processing was 13.32 ± 3.63 × 10⁸ and 10.63 ± 2.80 × 10⁸, respectively, and the recovery rate was 80.71 ± 11.26%. 0.4344 ± 0.1874% of the TNCs were CD34+ cells. The CFU-GM was 32.1 ± 28.0 colonies per 1 × 10⁵ nucleated cells. Based mainly on HLA and nucleated cell content, 26 UCB units were released for transplantation.

Conclusions

A public UCB bank was successfully established in China; collection and processing of UCB units should be optimized in order to gain maximum volume and cell count.     

A protocol for resuscitation of severe burn patients guided by transpulmonary thermodilution and lactate levels: a 3-year prospective cohort study

Introduction

The use of urinary output and vital signs to guide initial burn resuscitation may lead to suboptimal resuscitation. Invasive hemodynamic monitoring may result in over-resuscitation. This study aimed to evaluate the results of a goal-directed burn resuscitation protocol that used standard measures of mean arterial pressure (MAP) and urine output, plus transpulmonary thermodilution (TPTD) and lactate levels to adjust fluid therapy to achieve a minimum level of preload to allow for sufficient vital organ perfusion.

Methods

We conducted a three-year prospective cohort study of 132 consecutive critically burned patients. These patients underwent resuscitation guided by MAP (>65 mmHg), urinary output (0.5 to 1 ml/kg), TPTD and lactate levels. Fluid therapy was adjusted to achieve a cardiac index (CI) >2.5 L/minute/m² and an intrathoracic blood volume index (ITBVI) >600 ml/m², and to optimize lactate levels. Statistical analysis was performed using mixed models. We also used Pearson or Spearman methods and the Mann-Whitney U-test.

Results

A total of 98 men and 34 women (mean age, 48 ± 18 years) was studied. The mean total body surface area (TBSA) burned was 35% ± 22%. During the early resuscitation phase, lactate levels were elevated (2.58 ± 2.05 mmol/L) and TPTD showed initial hypovolemia by the CI (2.68 ± 1.06 L/minute/m²) and the ITBVI (709 ± 254 mL/m²). At 24 to 32 hours, the CI and lactic levels were normalized, although the ITBVI remained below the normal range (744 ± 276 ml/m²). The mean fluid rate required to achieve protocol targets in the first 8 hours was 4.05 ml/kg/TBSA burned, which slightly increased in the next 16 hours. Patients with a urine output greater than or less than 0.5 ml/kg/hour did not show differences in heart rate, mean arterial pressure, CI, ITBVI or lactate levels.

Conclusions

Initial hypovolemia may be detected by TPTD monitoring during the early resuscitation phase. This hypovolemia might not be reflected by blood pressure and hourly urine output. An adequate CI and tissue perfusion can be achieved with below-normal levels of preload. Early resuscitation guided by lactate levels and below-normal preload volume targets appears safe and avoids unnecessary fluid input.     

THE VALIDITY OF PLANTARFLEXOR STRENGTH MEASURES OBTAINED THROUGH HAND‐HELD DYNAMOMETRY MEASUREMENTS OF FORCE

Purpose/Background:

Hand‐held dynamometers are commonly used to assess plantarflexor strength during rehabilitation. The purpose of this study was to determine the concurrent validity of measuring plantarflexion force using a hand‐held dynamometer (HHD) as compared to an electromechanical dynamometer as the gold standard. The hypothesis was that plantarflexor forces obtained using a hand‐held dynamometer would not show absolute agreement with a criterion standard.

Design:

Concurrent validity assessment for a diagnostic strength testing device.

Setting:

Institutional clinic and research laboratory

Participants:

Volunteer sample of healthy university students (N=20, 10 women, 10 men; 25.9±4.1 years).

Main Outcome Measure(s):

Maximal plantarflexion strength was measured using both a HHD and an electromechanical dynamometer (EMD) as a criterion measure.

Results:

Plantarflexor force measures with the HHD were significantly different (p<0.01) and not correlated with plantarflexor forces measured using the EMD for either limb (R² ≤ 0.09).

Conclusions:

Plantarflexor strength measurements acquired using HHD are different from those acquired using an EMD and are likely influenced by the strength of the examiner.

Level of Evidence:

Prospective cohort study, level II     

Gender differences in response to cold pressor test assessed with velocity-encoded cardiovascular magnetic resonance of the coronary sinus

Background

Gender-specific differences in cardiovascular risk are well known, and current evidence supports an existing role of endothelium in these differences. The purpose of this study was to assess non invasively coronary endothelial function in male and female young volunteers by myocardial blood flow (MBF) measurement using coronary sinus (CS) flow quantification by velocity encoded cine cardiovascular magnetic resonance (CMR) at rest and during cold pressor test (CPT).

Methods

Twenty-four healthy volunteers (12 men, 12 women) underwent CMR in a 3 Tesla MR imager. Coronary sinus flow was measured at rest and during CPT using non breath-hold velocity encoded phase contrast cine-CMR. Myocardial function and morphology were acquired using a cine steady-state free precession sequence.

Results

At baseline, mean MBF was 0.63 ± 0.23 mL·g^-1·min^-1 in men and 0.79 ± 0.21 mL·g^-1·min^-1 in women. During CPT, the rate pressure product in men significantly increased by 49 ± 36% (p < 0.0001) and in women by 52 ± 22% (p < 0.0001). MBF increased significantly in both men and women by 0.22 ± 0.19 mL·g^-1·min^-1 (p = 0.0022) and by 0.73 ± 0.43 mL·g^-1·min^-1 (p = 0.0001), respectively. The increase in MBF was significantly higher in women than in men (p = 0.0012).

Conclusion

CMR coronary sinus flow quantification for measuring myocardial blood flow revealed a higher response of MBF to CPT in women than in men. This finding may reflect gender differences in endothelial-dependent vasodilatation in these young subjects. This non invasive rest/stress protocol may become helpful to study endothelial function in normal physiology and in physiopathology.     

Relationship between Leptin Levels and Suppressed CD4 Counts in HIV Patients

Objective

To examine the relationship between serum leptin levels and suppression of CD4 count in HIV-infected individuals with highly active antiretroviral therapy (HAART).

Subjects and Methods

Thirty seropositive HIV male patients selected from the Infectious Disease Hospital were classified into two groups according to their immunological and virological response to HAART. The first group included 15 male patients with low viral load and low CD4 counts; the second included 15 male patients with low viral load and high CD4 counts. Morning serum leptin and tumor necrosis factor-α levels of HIV patients were measured and correlated with fasting serum insulin, Homeostasis Model Assessment for Insulin Resistance (HOMA-IR), HIV viral load and CD4 count.

Results

Serum leptin levels were significantly higher in patients with high CD4 counts than in patients with low CD4 counts (mean serum leptin level 47.3 vs. 10.9 ng/ml, respectively; p < 0.0001). A positive correlation was observed between serum leptin levels and CD4 counts (r = 0.697; p < 0.0001); positive correlations were also seen between leptin levels and fasting serum insulin and HOMA-IR (r = 0.633, p < 0.0001, and r = 0.537, p < 0.003, respectively).

Conclusion

Serum leptin level was higher in HIV patients with high CD4 count and correlated with fasting serum insulin and HOMA-IR, thereby indicating that HAART treatment could lead to decreased levels of leptin in HIV patients, which might lead to impaired immunological recovery.Key Words: Human immunodeficiency virus, CD4 T cells, Leptin, Highly active antiretroviral therapy     

LOWER LIMB ASYMMETRIES IN RHYTHMIC GYMNASTICS ATHLETES

Background

Different limb training demands and limb preference may determine anthropometric and muscle force inter-limb asymmetries in Rhythmic Gymnastics (RG) athletes.

Purpose

The purpose of this study was to evaluate the influence of lateral preference of the lower extremity on anthropometric, range of motion, and isokinetic torque measurements of RG athletes.

Study Design

Cross sectional study

Methods

Lower limb anthropometric measurements (girth, estimated anatomical cross-sectional area), hip, knee and ankle range of motion, flexor and extensor isokinetic torques (angular velocities = 60, 180, e 240 °·s⁻¹) and bilateral asymmetry index were evaluated in 11 international level Rhythmic Gymnastics athletes (17.9 ± 4.0 years of age; 9.1 ± 5,1 years of experience; 26.8 ± 6.0 weekly training hours).

Results

The preferred limb showed larger thigh girth and anatomical cross-sectional area, higher ankle dorsiflexor range of motion, higher hip flexor torque at 60 °·s⁻¹ and higher plantarflexor torque at 180 °·s⁻¹ compared to the non-preferred limb.

Conclusions

The observed differences seem to be strictly related to lateral preference and rhythmic gymnastics training.

Levels of Evidence

3     

Prepregnancy SHBG Concentrations and Risk for Subsequently Developing Gestational Diabetes Mellitus

OBJECTIVE

Lower levels of sex hormone–binding globulin (SHBG) have been associated with increased risk of diabetes among postmenopausal women; however, it is unclear whether they are associated with glucose intolerance in younger women. We examined whether SHBG concentrations, measured before pregnancy, are associated with risk of gestational diabetes mellitus (GDM).

RESEARCH DESIGN AND METHODS

This was a nested case-control study among women who participated in the Kaiser Permanente Northern California Multiphasic Health Check-up examination (1984–1996) and had a subsequent pregnancy (1984–2009). Eligible women were free of recognized diabetes. Case patients were 256 women in whom GDM developed. Two control subjects were selected for each case patient and were matched for year of blood draw, age at examination, age at pregnancy, and number of intervening pregnancies.

RESULTS

Compared with the highest quartile of SHBG concentrations, the odds of GDM increased with decreasing quartile (odds ratio 1.06 [95% CI 0.44–2.52]; 2.33 [1.07–5.09]; 4.06 [1.90–8.65]; P for trend < 0.001), after adjusting for family history of diabetes, prepregnancy BMI, race/ethnicity, alcohol use, prepregnancy weight changes, and homeostasis model assessment of insulin resistance. Having SHBG levels below the median (<64.5 nmol/L) and a BMI ≥25.0 kg/m² was associated with fivefold increased odds of GDM compared with normal-weight women with SHBG levels at or above the median (5.34 [3.00–9.49]).

CONCLUSIONS

Low prepregnancy SHBG concentrations were associated with increased risk of GDM and might be useful in identifying women at risk for GDM for early prevention strategies.     

Nicotinuric Acid: A potential marker of metabolic syndrome through a metabolomics-based approach

OBJECTIVE

Metabolic syndrome is a multiplex disorder and puts patients on the road to type 2 diabetes and atherosclerotic cardiovascular diseases. However, a surrogate biomarker in plasma or urine in fully reflecting features of metabolic syndrome has not been explored.

RESEARCH DESIGN AND METHODS

Urine metabolomics has potential utility in metabolic profiling because urine metabolites analysis reflects global outflux of metabolic change. Accordingly, we collected data on subjects (n = 99) with overweight, dyslipidemia, hypertension or impaired glucose tolerance and took a metabolomics approach to analyze the metabolites of urine revealed in metabolic syndrome by high-performance liquid chromatography–time-of-flight mass spectrometry and elicit potential biomarkers to picture metabolic syndrome.

RESULTS

Our results revealed that the urine nicotinuric acid value of subjects with diabetes (HbA_1c ≥6.5% or those receiving diabetes medications) (n = 25) was higher than subjects without diabetes (n = 37) (221 ± 31 vs. 152 ± 13 × 10³ mAU, P = 0.0268). Moreover, urinary nicotinuric acid level was positively correlated with body mass index, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triacylglycerol and high sensitivity C-reactive protein, but negatively correlated with high-density lipoprotein cholesterol.

CONCLUSIONS

This is the first study, to our knowledge, to propose that nicotinuric acid represents an important pathogenic mechanism in process from metabolic syndrome to diabetes and atherosclerotic cardiovascular disease.Metabolic syndrome is a multifaceted disorder and considered to be a major cause of type 2 diabetes and atherosclerotic cardiovascular diseases. Although urine metabolomics has potential utility in metabolic profiling because urine metabolites reveal a global outflux of metabolic change, a surrogate biomarker in urine that fully reflects features of metabolic syndrome has not been explored. The aim of this study was to isolate a potential biomarker of metabolic syndrome through analysis of urine metabolites in subjects with features of metabolic syndrome.     

Frequency of Morning Ketosis After Overnight Insulin Suspension Using an Automated Nocturnal Predictive Low Glucose Suspend System

OBJECTIVE

To assess the effect of overnight insulin pump suspension in an automated predictive low glucose suspend system on morning blood glucose and ketone levels in an attempt to determine whether routine measurement of ketone levels is useful when a closed-loop system that suspends insulin delivery overnight is being used.

RESEARCH DESIGN AND METHODS

Data from an in-home randomized trial of 45 individuals with type 1 diabetes (age range 15–45 years) were analyzed, evaluating an automated predictive low glucose pump suspension system in which blood glucose, blood ketone, and urine ketone levels were measured on 1,954 mornings.

RESULTS

One or more pump suspensions occurred during 744 of the 977 intervention nights (76%). The morning blood ketone level was ≥0.6 mmol/L after 11 of the 744 nights (1.5%) during which a pump suspension occurred and 2 of the 233 nights (0.9%) during which there was no suspension compared with 11 of 977 control nights (1.1%). The morning blood ketone level was ≥0.6 mmol/L after only 2 of 159 nights (1.3%) with a pump suspension exceeding 2 h. Morning fasting blood glucose level was not a good predictor of the presence of blood ketones.

CONCLUSIONS

Routine measurement of blood or urine ketones during use of an automated pump suspension system using continuous glucose monitoring, whether threshold based or predictive, is not necessary. Recommendations for checking ketone levels should be no different when a patient is using a system with automated insulin suspension than it is for conventional diabetes self-management.     

Contraceptive practices and attitudes among immigrant and nonimmigrant women in Canada

Objective

To compare experiences, attitudes, and beliefs of immigrant and nonimmigrant women presenting for abortion with regard to contraception, and to identify difficulties involved in accessing contraception in Canada.

Design

A survey of immigrant and nonimmigrant women asking about women’s experiences with and attitudes toward contraceptives and any barriers to contraceptive access they have encountered. Demographic data including ethnicity, country of origin, and length of residence in Canada were collected.

Setting

Two urban abortion clinics.

Participants

Women presenting for first-trimester abortion.

Main outcome measures

Type of contraception used when the unwanted pregnancy was conceived, attitudes to contraceptives, and barriers to access of contraceptives.

Results

A total of 999 women completed questionnaires during the study period (75.9% response rate); 466 of them (46.6%) were born in Canada. Immigrant women presenting for abortion were less likely to be using hormonal contraception when they got pregnant (12.5% vs 23.5%, P < .001) and had more negative attitudes toward hormonal contraception (62.6% vs 51.6%, P < .003). They reported having more difficulties accessing contraception before the abortion (24.8% vs 15.3%, P < .001) than nonimmigrant women did. About half of all the women expressed fear about intrauterine device use. The longer immigrant women had lived in Canada, the more likely they were to have similar responses to those of Canadian-born women.

Conclusion

The information provided by this study might be valuable for family doctors and other clinicians to improve contraceptive information resources for immigrants to address existing knowledge gaps and other culturally relevant concerns. As about half of all women presenting for abortion expressed negative attitudes toward the more effective methods of contraception, it is important that family doctors educate all women at risk for unintended pregnancies.     

Clinical relevance of procalcitonin and C-reactive protein as infection markers in renal impairment: a cross-sectional study

Introduction

Although the clinical application of procalcitonin (PCT) as an infection marker in patients with impaired renal function (estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m²) has been increasing recently, it is unclear whether PCT is more accurate than C-reactive protein (CRP). We investigated the clinical value of CRP and PCT based on renal function.

Methods

From November 2008 to July 2011, a total of 493 patients who simultaneously underwent CRP and PCT tests were enrolled. The area under the receiver operating characteristic (ROC) curve and characteristics of both markers were analyzed according to infection severity and renal function.

Results

In patients with impaired renal function, the area under the ROC curve was 0.876 for CRP and 0.876 for PCT. In patients with infection, CRP levels differed depending on whether the infection was localized, septic, or severely septic, whereas PCT levels were higher in patients with severe sepsis or septic shock. In patients without infection, CRP did not correlate with eGFR, while PCT was negatively correlated with eGFR.

Conclusion

This study demonstrates that CRP is accurate for predicting infection in patients with impaired renal function. The study suggests that in spite of its higher cost, PCT is not superior to CRP as an infection marker in terms of diagnostic value.     

PINOT NOIR: Pulmonic INsufficiency imprOvemenT with Nitric Oxide Inhalational Response

Background

Tetralogy of Fallot (TOF) repair and pulmonary valvotomy for pulmonary stenosis (PS) lead to progressive pulmonary insufficiency (PI), right ventricular enlargement and dysfunction. This study assessed whether pulmonary regurgitant fraction measured by cardiovascular magnetic resonance (CMR) could be reduced with inhaled nitric oxide (iNO).

Methods

Patients with at least moderate PI by echocardiography undergoing clinically indicated CMR were prospectively enrolled. Patients with residual hemodynamic lesions were excluded. Ventricular volume and blood flow sequences were obtained at baseline and during administration of 40 ppm iNO.

Results

Sixteen patients (11 with repaired TOF and 5 with repaired PS) completed the protocol with adequate data for analysis. The median age [range] was 35 [19–46] years, BMI was 26 ± 5 kg/m² (mean ± SD), 50% were women and 75% were in NYHA class I. Right ventricular end diastolic volume index for the cohort was 157 ± 33 mL/m², end systolic volume index was 93 ± 20 mL/m² and right ventricular ejection fraction was 40 ± 6%. Baseline pulmonary regurgitant volume was 45 ± 25 mL/beat and regurgitant fraction was 35 ± 16%. During administration of iNO, regurgitant volume was reduced by an average of 6 ± 9% (p=0.01) and regurgitant fraction was reduced by an average of 5 ± 8% (p=0.02). No significant changes were observed in ventricular indices for either the left or right ventricle.

Conclusion

iNO was successfully administered during CMR acquisition and appears to reduce regurgitant fraction in patients with at least moderate PI suggesting a potential role for selective pulmonary vasodilator therapy in these patients.

Trials registration

ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT00543933","term_id":"NCT00543933"}}NCT00543933     

Ultrasound in the evaluation of interstitial pneumonia

Background

The diagnostic value of thoracic ultrasonography (US) has recently increased. Skilled sonographers with experience in pulmonary medicine have demonstrated the existence of US signs of chest pathology.

Purpose

To detect US findings associated with infectious interstitial pneumonia that can be used to supplement other diagnostic tools.

Materials and methods

Over a period of 5 years (2001–2006), 55 patients were referred to our ultrasonography units for evaluation of probable viral or viral-like infections of the respiratory tract. Each patient was subjected to a work-up that included clinical examination, blood tests, pulmonary function tests, bronchoscopy, chest radiographs, high-resolution computed tomography (HRCT), and thoracic US, which was performed under blinded conditions.

Results

Based on the findings that emerged from the work-up described above, all 55 patients were diagnosed with interstitial pneumonia. Evaluation of the US scans for the signs of interstitial lung disease described by Lichtenstein revealed “comet-tail” artifacts in the anterolateral lung fields in 31 (56.36%) patients and mixed patterns consisting in increased density associated with ring-down artifacts in 24 (46.64%). Pleural involvement was also observed in 34 cases (61.82%).

Conclusions

Thoracic US appears to be a useful adjunct to clinical, laboratory and radiological studies in patients suspected of having infectious interstitial pneumonia.     

High-mobility group box 1 and the receptor for advanced glycation end products contribute to lung injury during Staphylococcus aureus pneumonia

Introduction

Staphylococcus (S.) aureus has emerged as an important cause of necrotizing pneumonia. Lung injury during S. aureus pneumonia may be enhanced by local release of damage associated molecular patterns such as high-mobility group box 1 (HMGB1). In the current study we sought to determine the functional role of HMGB1 and its receptors, toll-like receptor 4 (TLR4) and the receptor for advanced glycation end products (RAGE), in the injurious host response to S. aureus pneumonia.

Methods

Pneumonia was induced in wild type (Wt), TLR4 deficient (tlr4^−/−) and RAGE deficient (rage^−/−) mice by intranasal inoculation of 1 × 10⁷ colony-forming units (CFU) of a USA300 S. aureus. In a separate set of experiments, Wt mice were injected intraperitoneally with a monoclonal anti-HMGB1 antibody or an isotype matched control antibody immediately before and every 24 hours after intranasal infection of S. aureus. Mice were sacrificed at 6, 24, 48 or 72 hours after infection for harvesting of blood and organs.

Results

S. aureus pneumonia was associated with HMGB1 release in the bronchoalveolar compartment peaking after 24 hours. Anti-HMGB1 attenuated lung pathology and protein leak and reduced interleukin-1β release 6 hours after infection, but not at later time points. RAGE deficiency more modestly attenuated lung pathology without influencing protein leak, while TLR4 deficiency did not impact on lung injury.

Conclusion

These data suggest that HMGB1 and RAGE, but not TLR4, contribute to lung injury accompanying the early phase of S. aureus pneumonia.     

The Comparative Effectiveness of Diabetes Prevention Strategies to Reduce Postpartum Weight Retention in Women With Gestational Diabetes Mellitus: The Gestational Diabetes’ Effects on Moms (GEM) Cluster Randomized Controlled Trial

OBJECTIVE

To compare the effectiveness of diabetes prevention strategies addressing postpartum weight retention for women with gestational diabetes mellitus (GDM) delivered at the health system level: mailed recommendations (usual care) versus usual care plus a Diabetes Prevention Program (DPP)–derived lifestyle intervention.

RESEARCH DESIGN AND METHODS

This study was a cluster randomized controlled trial of 44 medical facilities (including 2,280 women with GDM) randomized to intervention or usual care. The intervention included mailed gestational weight gain recommendations plus 13 telephone sessions between 6 weeks and 6 months postpartum. Primary outcomes included the following: proportion meeting the postpartum goals of 1) reaching pregravid weight if pregravid BMI <25.0 kg/m² or 2) losing 5% of pregravid weight if BMI ≥25.0 kg/m²; and pregravid to postpartum weight change.

RESULTS

On average, over the 12-month postpartum period, women in the intervention had significantly higher odds of meeting weight goals than women in usual care (odds ratio [OR] 1.28 [95% CI 1.10, 1.47]). The proportion meeting weight goals was significantly higher in the intervention than usual care at 6 weeks (25.5 vs. 22.4%; OR 1.17 [1.01, 1.36]) and 6 months (30.6 vs. 23.9%; OR 1.45 [1.14, 1.83]). Condition differences were reduced at 12 months (33.0 vs. 28.0%; OR 1.25 [0.96, 1.62]). At 6 months, women in the intervention retained significantly less weight than women in usual care (mean 0.39 kg [SD 5.5] vs. 0.95 kg [5.5]; mean condition difference −0.64 kg [95% CI −1.13, −0.14]) and had greater increases in vigorous-intensity physical activity (mean condition difference 15.4 min/week [4.9, 25.8]).

CONCLUSIONS

A DPP-derived lifestyle intervention modestly reduced postpartum weight retention and increased vigorous-intensity physical activity.     

Single breath-hold assessment of cardiac function using an accelerated 3D single breath-hold acquisition technique - comparison of an intravascular and extravascular contrast agent

Background

Cardiovascular magnetic resonance (CMR) is the current gold standard for the assessment of left ventricular (LV) function. Repeated breath-holds are needed for standard multi-slice 2D cine steady-state free precession sequences (M2D-SSFP). Accelerated single breath-hold techniques suffer from low contrast between blood pool and myocardium. In this study an intravascular contrast agent was prospectively compared to an extravascular contrast agent for the assessment of LV function using a single-breath-hold 3D-whole-heart cine SSFP sequence (3D-SSFP).

Methods

LV function was assessed in fourteen patients on a 1.5 T MR-scanner (Philips Healthcare) using 32-channel coil technology. Patients were investigated twice using a 3D-SSFP sequence (acquisition time 18–25 s) after Gadopentetate dimeglumine (GdD, day 1) and Gadofosveset trisodium (GdT, day 2) administration. Image acquisition was accelerated using sensitivity encoding in both phase encoding directions (4xSENSE). CNR and BMC were both measured between blood and myocardium. The CNR incorporated noise measurements, while the BMC represented the coeffiancy between the signal from blood and myocardium [1]. Contrast to noise ratio (CNR), blood to myocardium contrast (BMC), image quality, LV functional parameters and intra-/interobserver variability were compared. A M2D-SSFP sequence was used as a reference standard on both days.

Results

All 3D-SSFP sequences were successfully acquired within one breath-hold after GdD and GdT administration. CNR and BMC were significantly (p < 0.05) higher using GdT compared to GdD, resulting in an improved endocardial definition. Using 3D-SSFP with GdT, Bland–Altman plots showed a smaller bias (95% confidence interval LVEF: 9.0 vs. 23.7) and regression analysis showed a stronger correlation to the reference standard (R² = 0.92 vs. R² = 0.71), compared to 3D-SSFP with GdD.

Conclusions

A single-breath-hold 3D-whole-heart cine SSFP sequence in combination with 32-channel technology and an intravascular contrast agent allows for the accurate and fast assessment of LV function.

Trial registration

The study was approved by the local research ethics committee (Study No. 07/Q0704/2) and was registered with the Medicines and Healthcare Products Regulatory Agency (MHRA Study No. 28482/0002/001–0001, EudraCTnumber 2006–007042).     

Procalcitonin testing for diagnosis and short-term prognosis in bacterial infection complicated by congestive heart failure: a multicenter analysis of 4,698 cases

Introduction

Procalcitonin (PCT) is a biomarker for the clinical diagnosis of bacterial infection that is more specific and earlier than fever, changes in white blood cell count, and blood cultures. Congestive heart failure is an important cause of endotoxin resorption from the intestine, which significantly increases PCT expression in noninfected patients with heart failure. The diagnostic performance and cut-off value of PCT in patients with bacterial infection complicated by congestive heart failure needs to be confirmed.

Methods

A total of 4,698 cases from different cities in China, including those with different classes of congestive heart failure, bacterial infection, bacterial infection complicated by heart failure and healthy individuals, were chosen for the diagnostic value analysis of PCT and screening candidate predictors of mortality in subjects with bacterial infection complicated by congestive heart failure.

Results

Patients with simple heart failure had significantly higher PCT levels than normal controls (P < 0.01), whereas patients with bacterial infection complicated by congestive heart failure had significantly higher PCT levels than those with simple infection (P < 0.01). Although it was useful for the diagnosis of infection (area under the receiver operating characteristic curve >80%), the positive predictive value of PCT decreased significantly with increasing severity of heart failure (P < 0.05), and the cut-off value of PCT concentrations for infection complicated by classes II, III and IV heart failure were 0.086, 0.192 and 0.657 μg/L, respectively. Heart failure degree, PCT level, and age were the candidate predictors of mortality in patients with bacterial infection complicated by congestive heart failure.

Conclusions

These data suggest that complicated heart failure elevates the PCT level in patients with bacterial infection. Thus, the results of the PCT test must be analyzed correctly in consideration of the severity of heart failure. Close attention should be paid to cardiac function and PCT expression in aged patients with infection complicated by congestive heart failure.