A Novel Monoclonal Antibody Degrades the Thyrotropin Receptor Autoantibodies in Graves' Disease

ObjectiveAutoantibodies against the thyrotropin receptor (TSH-R-Ab) are key mediators for the pathogenesis of Graves' disease (GD). TSH-R-Ab degradation was evaluated using several immunoassays within an exploratory, controlled trial in patients with GD receiving a monoclonal antibody (mAb) targeting the neonatal crystallizable fragment receptor (FcRn).MethodsSerial measurements of TSH-R-Ab serum levels were performed using 3 different binding and cell-based assays in patients with GD either on medication or on placebo.ResultsIn contrast to the placebo group, in which no changes were observed, a 12-week mAb therapy led to an early and significant decrease (>60%) in the serum TSH-R-Ab levels in patients with thyroidal and extrathyroidal GD, as unanimously shown in all 3 assays. These marked changes were noted already at week 7 post baseline (P <.0001 for the binding immunoassay and for the luciferase (readout) bioassay). The 3 TSH-R-Ab binding and bioassays were highly correlated in the samples of both study groups (binding immunoassay vs luciferase bioassay, r =.91, P <.001, binding vs cyclic adenosine monophosphate (cAMP) bioassay, r = 0.86, P <.001, and luciferase vs cAMP bioassay, r = 0.71, P =.006). The serological results correlated with the course of the extrathyroidal clinical parameters of GD, that is, clinical activity score and proptosis.ConclusionTargeting the FcRn markedly reduces the disease-specific TSH-R-Ab in patients with GD. The novel and rapid TSH-R-Ab bioassay improves diagnosis and management of patients with GD.     

Clinical Outcome among Nasopharyngeal Cancer Patients in a Multi-Ethnic Society in Singapore

BackgroundNasopharyngeal cancer (NPC) is endemic among Chinese populations in Southeast Asia. However, the outcomes of non-Chinese NPC patients in Singapore are not well reported.AimTo determine if non-Chinese NPC patients have a different prognosis and examine the clinical outcomes of NPC patients in a multi-ethnic society.MethodsRetrospective chart review of 558 NPC patients treated at a single academic tertiary hospital from 2002 to 2012. Survival and recurrence rates were analysed and predictive factors identified using the Kaplan-Meier method and Cox regression model.ResultsOur cohort comprised 409 males (73.3%) and 149 females (26.7%) with a median age of 52 years. There were 476 Chinese (85.3%), 57 Malays (10.2%), and 25 of other ethnic groups (4.5%). Non-Chinese patients were more likely to be associated with advanced nodal disease at initial presentation (p = 0.049), compared with the Chinese. However, there were no statistical differences in their overall survival (OS) or disease specific survival (DSS) (p = 0.934 and p = 0.857 respectively). The 3-year and 5-year cohort OS and DSS rates were 79.3%, 70.7%, and 83.2%, 77.4% respectively. Advanced age (p<0.001), N2 disease (p = 0.036), N3 disease (p<0.001), and metastatic disease (p<0.001) at presentation were independently associated with poor overall survival. N2 disease (p = 0.032), N3 disease (p<0.001) and metastatic disease (p<0.001) were also independently associated with poor DSS. No predictive factors were associated with loco-regional recurrence after definitive treatment. Advanced age (p = 0.044), N2 disease (p = 0.033) and N3 disease (p<0.001) were independently associated with distant relapse.ConclusionIn a multi-ethnic society in Singapore, non-Chinese are more likely to present with advanced nodal disease. This however did not translate into poorer survival outcomes. Older patients with N2 or N3 disease are associated with a higher risk of distant relapse and poor overall survival.     

Cohorting Dengue Patients Improves the Quality of Care and Clinical Outcome

IntroductionThe increasing incidence of dengue among adults in Malaysia and other countries has important implications for health services. Before 2004, in order to cope with the surge in adult dengue admissions, each of the six medical wards in a university hospital took turns daily to admit and manage patients with dengue. Despite regular in-house training, the implementation of the WHO 1997 dengue case management guidelines by the multiple medical teams was piecemeal and resulted in high variability of care. A restructuring of adult dengue inpatient service in 2004 resulted in all patients being admitted to one ward under the care of the infectious disease unit. Hospital and Intensive Care Unit admission criteria, discharge criteria and clinical laboratory testing were maintained unchanged throughout the study period.ObjectivesTo evaluate the impact of cohorting adult dengue patients on the quality of care and the clinical outcome in a university hospital in Malaysia.MethodsA pre (2003) and post-intervention (2005–6) retrospective study was undertaken.InterventionCohorting all dengue patients under the care of the Infectious Disease team in a designated ward in 2004.ResultsThe number of patients enrolled was 352 in 2003, 785 in 2005 and 1158 in 2006. The evaluation and detection of haemorrhage remained high (>90%) and unchanged throughout the study period. The evaluation of plasma leakage increased from 35.4% pre-intervention to 78.8% post-intervention (p = <0.001) while its detection increased from 11.4% to 41.6% (p = <0.001). Examination for peripheral perfusion was undertaken in only 13.1% of patients pre-intervention, with a significant increase post-intervention, 18.6% and 34.2% respectively, p = <0.001. Pre-intervention, more patients had hypotension (21.5%) than detected peripheral hypoperfusion (11.4%), indicating that clinicians recognised shock only when patients developed hypotension. In contrast, post-intervention, clinicians recognised peripheral hypoperfusion as an early sign of shock. The highest haematocrit was significantly higher post-intervention but the lowest total white cell counts and platelet counts remained unchanged. A significant and progressive reduction in the use of platelet transfusions occurred, from 21.7% pre-intervention to 14.6% in 2005 and 5.2% in 2006 post-intervention, p<0.001. Likewise, the use of plasma transfusion decreased significantly from 6.1% pre-intervention to 4.0% and 1.6% in the post-intervention years of 2005 and 2006 respectively, p<0.001. The duration of intravenous fluid therapy decreased from 3 days pre-intervention to 2.5 days (p<0.001) post-intervention; the length of hospital stay reduced from 4 days pre- to 3 days (p<0.001) post-intervention and the rate of intensive care admission from 5.8% pre to 2.6% and 2.5% post-intervention, p = 0.005.ConclusionCohorting adult dengue patients under a dedicated and trained team of doctors and nurses led to a substantial improvement in quality of care and clinical outcome.     

Clinical characteristics and risk factors for severe scrub typhus in pediatric and elderly patients

BackgroundScrub typhus (ST) is a life-threatening infectious disease if appropriate treatment is unavailable. Large discrepancy of clinical severity of ST patients was reported among age groups, and the underlying risk factors for severe disease are unclear.MethodsClinical and epidemiological data of ST patients were collected in 55 surveillance hospitals located in Guangzhou City, China, from 2012 to 2018. Severe prognosis and related factors were determined and compared between pediatric and elderly patients.ResultsA total of 2,074 ST patients including 209 pediatric patients and 1,865 elderly patients were included, with a comparable disease severity rate of 11.0% (95% CI 7.1%–16.1%) and 10.3% (95% CI 9.0%–11.8%). Different frequencies of clinical characteristics including lymphadenopathy, skin rash, enlarged tonsils, etc. were observed between pediatric and elderly patients. Presence of peripheral edema and decreased hemoglobin were the most important predictors of severe illness in pediatric patients with adjusted ORs by 38.99 (9.96–152.67, p<0.001) and 13.22 (1.54–113.50, p = 0.019), respectively, while presence of dyspnea and increased total bilirubin were the potential determinants of severe disease in elderly patients with adjusted ORs by 11.69 (7.33–18.64, p<0.001) and 3.17 (1.97–5.11, p<0.001), respectively. Compared with pediatric patients, elderly patients were more likely to receive doxycycline (64.8% v.s 9.9%, p<0.001), while less likely to receive azithromycin therapy (5.0% v.s 41.1%, p<0.001).ConclusionThe disease severity rate is comparable between pediatric and elderly ST patients, while different clinical features and laboratory indicators were associated with development of severe complications for pediatric and elderly patients, which is helpful for diagnosis and progress assessment of disease for ST patients.     

Binding, stimulating and blocking TSH receptor antibodies to the thyrotropin receptor as predictors of relapse of Graves' disease after withdrawal of antithyroid treatment.

TSH-receptor autoantibodies (TRAbs) are a valuable diagnostic tool for confirming a diagnosis of Graves' disease (GD). While there is evidence that high TRAb levels are associated with relapse of GD, whether a discrimination of TRAb into stimulating (TSAb) and blocking (TBAb) autoantibodies would benefit the clinician in terms of outcome prediction remains unclear. To address this issue, we have determined TRAb, TSAb and TBAb levels in serum samples of ninety-six euthyroid patients with GD taken four weeks after antithyroid drug withdrawal (ATDT). Forty-seven patients (49 %) underwent relapse of GD within two years. Amongst those, forty-one (87 %) had been positive for TRAb and thirty-five (74 %) for TSAb after treatment. All patients except one were negative for TBAb. The correlation between TRAb and TSAb in those treated GD patients was relatively weak (r = 0.268, p < 0.001). Based on a cut-off limit of 1.5 IU/l, the positive and negative predictive values with respect to prediction of relapse were too low for any clinical relevance (TRAb: 49 % and 54 %; TSAb: 51 % and 55 %). However, when a cut-off level above 10 IU/l was used, the positive and negative predictive values increased to 83 % and 62 %. The additional measurement of TSAb or TBAb in those samples after therapy did not add additional information, even at higher decision thresholds. In conclusion, differentiation of TRAb into TSAb and TBAb is of no help in the prediction of relapse of GD in euthyroid patients at the end of ATDT, and only high TRAb levels are associated with relapse.     

Oxidants and antioxidants in myocardial infarction (MI): Investigation of ischemia modified albumin,malondialdehyde, superoxide dismutase and catalase in individuals diagnosed with ST elevated myocardial infarction (STEMI) and non-STEMI (NSTEMI)

BackgroundCoronary ischemia can lead to myocardial damage and necrosis. The pathogenesis of cardiovascular diseases often includes increased oxidative stress and decreased antioxidant defense. The study aimed to assess levels of ischemia modified albumin (IMA), malondialdehyde acid (MDA), superoxide dismutase (SOD), and catalase in individuals diagnosed with ST elevated myocardial infarction (STEMI) and non-STEMI.MethodsThe present study prospectively included 50 STEMI patients, 55 NSTEMI patients, and 55 healthy subjects. Only patients who were recently diagnosed with STEMI or NSTEMI were included in this study. IMA, MDA, SOD, and catalase activities were measured spectrophotometrically. Significant coronary artery lesions were determined by angiography.ResultsPatients with ACS had significantly greater IMA and MDA values than the healthy controls (p<0.001). Besides, patients with STEMI had IMA levels that were significantly greater than those of the patients with NSTEMI (p<0.001), while the reverse was true for MDA levels (p<0.001). The healthy controls had the highest levels of SOD and catalase levels, followed by patients with STEMI and patients with NSTEMI, respectively (p<0.001). There was a significant negative correlation among MDA and SOD with catalase levels (r = -0.771 p<0.001 MDA vs catalase; r = -0.821 p<0.001 SOD vs catalase).ConclusionsData obtained in this study reveals that compared to healthy controls, STEMI and NSTEMI patients had increased levels of MDA and IMA and decreased levels of SOD and catalase.     

Twenty Years of Medically-Attended Pediatric Varicella and Herpes Zoster in Ontario,Canada: A Population-Based Study

ObjectiveTo determine if reductions in medically-attended pediatric varicella and herpes zoster occurred in Ontario, Canada, after publicly-funded varicella immunization was implemented in 2004.MethodsFor fiscal years (FY) 1992-2011, we examined data on varicella and herpes zoster physician office visits, emergency department (ED) visits, hospitalizations (including for varicella-associated skin and soft tissue infections [SSTI]), and intensive care unit (ICU) admissions, among those aged <18 years. The pre-vaccine, privately-available, and vaccine program eras were FY1992-1998, FY1999-2003, and FY2004-2011, respectively. We used Poisson regressionand Kruskal-Wallis tests (all at the p<0.05 level of significance), and compared rates using incidence rate ratios (IRRs) and 95% confidence intervals (CIs).ResultsIncidence of varicella office visits declined over the study period from a high of 25.1/1,000 in FY1994 to a low of 3.2/1,000 in FY2011. ED visits and hospitalizations followed similar patterns of decreasing rates later in the study period. IRRs comparing the vaccine program versus pre-vaccine eras were 0.29 (95%CI: 0.26-0.32) for office visits, 0.29 (95%CI: 0.21-0.40) for ED visits, and 0.41 (95%CI: 0.10-1.69) for hospitalizations. Annual declines in varicella office visits were 7.7%, 9.1%, 8.4%, and 8.4% per year among children aged <1 year, 1-4 years, 5-11 years, and ≥12 years, respectively (all p<0.001). Age-specific rates of varicella-associated SSTI declined significantly among children <12 years (p<0.001) and rates of ICU admissions decreased significantly for children <1 year (p = 0.02). (p<0.001) over the study period. For children aged 5-17 years, herpes zoster office visits decreased whereas ED visits increased (both p<0.001) and there was a small, non-significant (p = 0.07), decrease in hospitalizations.ConclusionMedically-attended varicella decreased during the study period, particularly since varicella vaccine was publicly-funded. Results suggest immunization program-related changes in varicella epidemiology, including herd effects, demonstrated by reductions in varicella in program-ineligible age groups. We did not observe a consistent impact on herpes zoster.     

Mitochondria DNA Change and Oxidative Damage in Clinically Stable Patients with Major Depressive Disorder

BackgroundTo compare alterations of mitochondria DNA (mtDNA) copy number, single nucleotide polymorphisms (SNPs), and oxidative damage of mtDNA in clinically stable patients with major depressive disorder (MDD).MethodsPatients met DSM-IV diagnostic criteria for MDD were recruited from the psychiatric outpatient clinic at Changhua Christian Hospital, Taiwan. They were clinically stable and their medications had not changed for at least the preceding two months. Exclusion criteria were substance-induced psychotic disorder, eating disorder, anxiety disorder or illicit substance abuse. Comparison subjects did not have any major psychiatric disorder and they were medically healthy. Peripheral blood leukocytes were analyzed to compare copy number, SNPs and oxidative damage of mtDNA between the two groups.Results40 MDD patients and 70 comparison subjects were collected. The median age of the subjects was 42 years and 38 years in MDD and comparison groups, respectively. Leukocyte mtDNA copy number of MDD patients was significantly lower than that of the comparison group (p = 0.037). MDD patients had significantly higher mitochondrial oxidative damage than the comparison group (6.44 vs. 3.90, p<0.001). After generalized linear model adjusted for age, sex, smoking, family history, and psychotropic use, mtDNA copy number was still significantly lower in the MDD group (p<0.001). MtDNA oxidative damage was positively correlated with age (p<0.001) and MDD (p<0.001). Antipsychotic use was negatively associated with mtDNA copy number (p = 0.036).LimitationsThe study is cross-sectional with no longitudinal follow up. The cohort is clinically stable and generalizability of our result to other cohort should be considered.ConclusionsOur study suggests that oxidative stress and mitochondria may play a role in the pathophysiology of MDD. More large-scale studies are warranted to assess the interplay between oxidative stress, mitochondria dysfunction and MDD.     

Serum Malondialdehyde Levels in Patients with Malignant Middle Cerebral Artery Infarction Are Associated with Mortality

ObjectiveMalondialdehyde (MDA) is an end-product formed during lipid peroxidation, due to degradation of cellular membrane phospholipids. MDA is released into extracellular space and finally into the blood; it has been used as an effective biomarker of lipid oxidation. High circulating levels of MDA have been previously described in patients with ischemic stoke than in controls, and an association between circulating MDA levels and neurological functional outcome in patients with ischemic stoke. However, an association between serum MDA levels and mortality in patients with ischemic stroke has not been previously reported, and that was the objective of this study.MethodsObservational, prospective and multicenter study performed in six Intensive Care Units. We included patients with severe malignant middle cerebral artery infarction (MMCAI) defined as Glasgow Coma Scale (GCS) lower than 9. We measured serum MDA levels in 50 patients with severe MMCAI at the time of diagnosis and in 100 healthy subjects. Mortality at 30 days was the end point of the study.ResultsWe found that patients with severe MMCAI showed higher serum MDA levels than healthy subjects (p<0.001). We found higher serum MDA levels (p<0.001) in non-surviving MMCAI patients (n=26) than in survivors (n=24). The area under the curve for prediction of 30-day mortality for serum MDA levels was 0.77 (95% CI = 0.63-0.88; p<0.001). Serum MDA levels >2.27 nmol/mL were associated with 30-day mortality (OR=7.23; 95% CI=1.84-28.73; p=0.005) controlling for GCS and age on multiple binomial logistic regression analysis.ConclusionsTo our knowledge, this is the first study showing that serum malondialdehyde levels in patients with MMCAI are associated with early mortality.     

Robust and Reproducible Quantification of the Extent of Chest Radiographic Abnormalities (And It’s Free!)

RationaleObjective, reproducible quantification of the extent of abnormalities seen on a chest radiograph would improve the user-friendliness of a previously proposed severity scoring system for pulmonary tuberculosis and could be helpful in monitoring response to therapy, including in clinical trials.MethodsIn this study we report the development and evaluation of a simple tool using free image editing software (GIMP) to accurately and reproducibly quantify the area of affected lung on the chest radiograph of tuberculosis patients. As part of a pharmacokinetic study in Lima, Peru, a chest radiograph was performed on patients with pulmonary tuberculosis and this was subsequently photographed using a digital camera. The GIMP software was used by two independent and trained readers to estimate the extent of affected lung (expressed as a percentage of total lung area) in each radiograph and the resulting radiographic SCORE.Results56 chest radiographs were included in the reading analysis. The Intraclass correlation coefficient (ICC) between the 2 observers was 0.977 (p<0.001) for the area of lung affected and was 0.955 (p<0.001) for the final score; and the kappa coefficient of Interobserver agreement for both the area of lung affected and the score were 0.9 (p<0.001) and 0.86 (p<0.001) respectively.ConclusionsThis high level of between-observer agreement suggests that this freely available software could constitute a simple and useful tool for robust evaluation of individual and serial chest radiographs.     

Impact of Body Mass Index on In-Hospital Complications in Patients Undergoing Percutaneous Coronary Intervention in a Japanese Real-World Multicenter Registry

Background

Obesity is associated with advanced cardiovascular disease. However, some studies have reported the “obesity paradox” after percutaneous coronary intervention (PCI). The relationship between body mass index (BMI) and clinical outcomes after PCI has not been thoroughly investigated, especially in Asian populations.

Methods

We studied 10,142 patients who underwent PCI at 15 Japanese hospitals participating in the JCD-KICS registry from September 2008 to April 2013. Patients were divided into four groups according to BMI: underweight, BMI <18.5 (n=462); normal, BMI ≥18.5 and <25.0 (n=5,945); overweight, BMI ≥25.0 and <30.0 (n=3,100); and obese, BMI ≥30.0 (n=635).

Results

Patients with a high BMI were significantly younger (p<0.001) and had a higher incidence of coronary risk factors such as hypertension (p<0.001), hyperlipidemia (p<0.001), diabetes mellitus (p<0.001), and current smoking (p<0.001), than those with a low BMI. Importantly, patients in the underweight group had the worst in-hospital outcomes, including overall complications (underweight, normal, overweight, and obese groups: 20.4%, 11.5%, 8.4%, and 10.2%, p<0.001), in-hospital mortality (5.8%, 2.1%, 1.2%, and 2.7%, p<0.001), cardiogenic shock (3.5%, 2.0%, 1.5%, and 1.6%, p=0.018), bleeding complications (10.0%, 4.5%, 2.6%, and 2.8%, p<0.001), and receiving blood transfusion (7.6%, 2.7%, 1.6%, and 1.7%, p<0.001). BMI was inversely associated with bleeding complications after adjustment by multivariate logistic regression analysis (odds ratio, 0.95; 95% confidence interval, 0.92–0.98; p=0.002). In subgroup multivariate analysis of patients without cardiogenic shock, BMI was inversely associated with overall complications (OR, 0.98; 95% CI, 0.95–0.99; p=0.033) and bleeding complications (OR, 0.95; 95% CI, 0.91–0.98; p=0.006). Furthermore, there was a trend that BMI was moderately associated with in-hospital mortality (OR, 0.94; 95% CI, 0.88–1.01; p=0.091).

Conclusions

Lean patients, rather than obese patients are at greater risk for in-hospital complications during and after PCI, particularly for bleeding complications.     

Treatment Strategies and Survival of Older Breast Cancer Patients – An International Comparison between the Netherlands and Ireland

ObjectivesForty percent of breast cancers occur among older patients. Unfortunately, there is a lack of evidence for treatment guidelines for older breast cancer patients. The aim of this study is to compare treatment strategy and relative survival for operable breast cancer in the elderly between The Netherlands and Ireland.ResultsOverall, 41,055 patients from The Netherlands and 5,826 patients from Ireland were included. Overall, more patients received guideline-adherent locoregional treatment in The Netherlands, overall (80% vs. 68%, adjusted p<0.001), stage I (83% vs. 65%, p<0.001), stage II (80% vs. 74%, p<0.001) and stage III (74% vs. 57%, P<0.001) disease. On the other hand, more systemic treatment was provided in Ireland, where endocrine therapy was prescribed to 92% of hormone receptor-positive patients, compared to 59% in The Netherlands. In The Netherlands, only 6% received chemotherapy, as compared 24% in Ireland. But relative survival was poorer in Ireland (5 years relative survival 89% vs. 83%), especially in stage II (87% vs. 85%) and stage III (61% vs. 58%) patients.ConclusionTreatment for older breast cancer patients differed significantly on all treatment modalities between The Netherlands and Ireland. More locoregional treatment was provided in The Netherlands, and more systemic therapy was provided in Ireland. Relative survival for Irish patients was worse than for their Dutch counterparts. This finding should be a strong recommendation to study breast cancer treatment and survival internationally, with the ultimate goal to equalize the survival rates for breast cancer patients across Europe.     

Symptom Clusters in People Living with HIV Attending Five Palliative Care Facilities in Two Sub-Saharan African Countries: A Hierarchical Cluster Analysis

BackgroundSymptom research across conditions has historically focused on single symptoms, and the burden of multiple symptoms and their interactions has been relatively neglected especially in people living with HIV. Symptom cluster studies are required to set priorities in treatment planning, and to lessen the total symptom burden. This study aimed to identify and compare symptom clusters among people living with HIV attending five palliative care facilities in two sub-Saharan African countries.MethodsData from cross-sectional self-report of seven-day symptom prevalence on the 32-item Memorial Symptom Assessment Scale-Short Form were used. A hierarchical cluster analysis was conducted using Ward’s method applying squared Euclidean Distance as the similarity measure to determine the clusters. Contingency tables, X² tests and ANOVA were used to compare the clusters by patient specific characteristics and distress scores.ResultsAmong the sample (N=217) the mean age was 36.5 (SD 9.0), 73.2% were female, and 49.1% were on antiretroviral therapy (ART). The cluster analysis produced five symptom clusters identified as: 1) dermatological; 2) generalised anxiety and elimination; 3) social and image; 4) persistently present; and 5) a gastrointestinal-related symptom cluster. The patients in the first three symptom clusters reported the highest physical and psychological distress scores. Patient characteristics varied significantly across the five clusters by functional status (worst functional physical status in cluster one, p<0.001); being on ART (highest proportions for clusters two and three, p=0.012); global distress (F=26.8, p<0.001), physical distress (F=36.3, p<0.001) and psychological distress subscale (F=21.8, p<0.001) (all subscales worst for cluster one, best for cluster four).ConclusionsThe greatest burden is associated with cluster one, and should be prioritised in clinical management. Further symptom cluster research in people living with HIV with longitudinally collected symptom data to test cluster stability and identify common symptom trajectories is recommended.     

Gender Differences in In-Hospital Clinical Outcomes after Percutaneous Coronary Interventions: An Insight from a Japanese Multicenter Registry

Background

Gender differences in clinical outcomes after percutaneous coronary intervention (PCI) among different age groups are controversial in the era of drug-eluting stents, especially among the Asian population who are at higher risk for bleeding complications.

Methods and Results

We analyzed data from 10,220 patients who underwent PCI procedures performed at 14 Japanese hospitals from September 2008 to April 2013. A total of 2,106 (20.6%) patients were women. Women were older (72.7±9.7 vs 66.6±10.8 years, p<0.001), and had a lower body mass index (23.4±4.0 vs 24.3±3.5, p<0.001), with a higher prevalence of hypertension (p<0.001), hyperlipidemia (p<0.001), insulin-dependent diabetes (p<0.001), renal failure (p<0.001), and heart failure (p<0.001) compared with men. Men tended to have more bifurcation lesions (p = 0.003) and chronic totally occluded lesions (p<0.001) than women. Crude overall complications (14.8% vs 9.5%, p<0.001) and the rate of bleeding complications (5.3% vs 2.8%, p<0.001) were significantly higher in women than in men. On multivariate analysis in the total cohort, female sex was an independent predictor of overall complications (OR, 1.47; 95% CI, 1.26–1.71; p<0.001) and bleeding complications (OR, 1.74; 95% CI, 1.36–2.24; p<0.001) after adjustment for confounding variables. A similar trend was observed across the middle-aged group (≥55 and <75 years) and old age group (≥75 years).

Conclusions

Women are at higher risk than men for post-procedural complications after PCI, regardless of age.     

Dual Energy CT Angiography of Peripheral Arterial Disease: Feasibility of Using Lower Contrast Medium Volume

ObjectiveOne of the main drawbacks associated with Dual Energy Computed Tomography Angiography (DECTA) is the risk of developing contrast medium-induced nephropathy (CIN). The aim of the present study was firstly, to design an optimal CT imaging protocol by determining the feasibility of using a reduced contrast medium volume in peripheral arterial DECTA, and secondly, to compare the results with those obtained from using routine contrast medium volume.MethodsThirty four patients underwent DECTA for the diagnosis of peripheral arterial disease. They were randomly divided into two groups: Group 1 (routine contrast volume group) with n = 17, injection rate 4–5 ml/s, and 1.5 ml/kg of contrast medium, and Group 2 ((low contrast volume group), with n = 17, injection rate 4–5ml/s, and contrast medium volume 0.75 ml/kg. A fast kilovoltage—switching 64-slice CT scanner in the dual-energy mode was employed for the study. A total of 6 datasets of monochromatic images at 50, 55, 60, 65, 70 and 75 keV levels were reconstructed with adaptive statistical iterative reconstruction (ASIR) at 50%. A 4-point scale was the tool for qualitative analysis of results. The two groups were compared and assessed quantitatively for image quality on the basis of signal-to-noise ratio (SNR) and contrast-to-noise-ratio (CNR). Radiation and contrast medium doses were also compared.ResultsThe overall mean CT attenuation and mean noise for all lower extremity body parts was significantly lower for the low volume contrast group (p<0.001), and varied significantly between groups (p = 0.001), body parts (p<0.001) and keVs (p<0.001). The interaction between group body parts was significant with CT attenuation and CNR (p = 0.002 and 0.003 respectively), and marginally significant with SNR (p = 0.047), with minimal changes noticed between the two groups. Group 2 (low contrast volume group) displayed the lowest image noise between 65 and 70 keV, recorded the highest SNR and CNR at 65 keV, and produced significantly lower results with respect to contrast medium volume and duration of contrast injection (p<0.001). The effect of radiation dose was not statistically significant between the two groups.ConclusionsDECTA images created at 65 keV and 50% ASIR with low contrast medium volume protocol, yielded results that were comparable to routine contrast medium volume, with acceptable diagnostic images produced during the evaluation of peripheral arteries.     

Blindness and Glaucoma: A Multicenter Data Review from 7 Academic Eye Clinics

PurposeTo evaluate frequency, conversion rate, and risk factors for blindness in glaucoma patients treated in European Universities.MethodsThis multicenter retrospective study included 2402 consecutive patients with glaucoma in at least one eye. Medical charts were inspected and patients were divided into those blind and the remainder (‘controls’). Blindness was defined as visual acuity≤0.05 and/or visual field loss to less than 10°.ResultsUnilateral and bilateral blindness were respectively 11.0% and 1.6% at the beginning, and 15.5% and 3.6% at the end of the observation period (7.5±5.5 years, range:1–25 years); conversion to blindness (at least unilateral) was 1.1%/year. 134 eyes (97 patients) developed blindness by POAG during the study. At the first access to study centre, they had mean deviation (MD) of -17.1±8.3 dB and treated intraocular pressure (IOP) of 17.1±6.6 mmHg. During follow-up the IOP decreased by 14% in these eyes but MD deteriorated by 1.1±3.5 dB/year, which was 5-fold higher than controls (0.2±1.6 dB/year). In a multivariate model, the best predictors for blindness by glaucoma were initial MD (p<0.001), initial IOP (p<0.001), older age at the beginning of follow-up (p<0.001), whereas final IOP was found to be protective (p<0.05).ConclusionsIn this series of patients, blindness occurred in about 20%. Blindness by glaucoma had 2 characteristics: late diagnosis and/or late referral, and progression of the disease despite in most cases IOP was within the range of normality and target IOP was achieved; it could be predicted by high initial MD, high initial IOP, and old age.     

Association of Left Ventricular Mass with All-Cause Mortality,Myocardial Infarction and Stroke

Background

Our aim was to assess the association of left ventricular mass with mortality and nonfatal cardiovascular events.

Methodology/Principal Findings

Left ventricular mass was measured by echocardiography in 40138 adult patients (mean age 61.1±16.4 years, 52.5% male). The primary endpoint was all-cause mortality. Secondary endpoints included nonfatal myocardial infarction and nonfatal stroke. During a mean follow-up period of 5.6±3.9 years, 9181 patients died, 901 patients had a nonfatal myocardial infarction, and 2139 patients had a nonfatal stroke. Cumulative 10-year mortality was 26.8%, 31.9%, 37.4% and 46.4% in patients with normal, mildly, moderately and severely increased left ventricular mass, respectively (p<0.001). Ten-year rates of nonfatal myocardial infarction and stroke ranged from 3.2% and 6.7% in patients with normal left ventricular mass to 5.3% and 12.7% in those with severe increase in left ventricular mass, respectively. After multivariate adjustment, left ventricular mass remained an independent predictor of all-cause mortality (hazard ratio [HR] per 100 g increase 1.21, 95% confidence interval [CI] 1.14–1–27, p<0.001 in women, and HR 1.09, 95% CI 1.04–1–13, p<0.001 in men), myocardial infarction (HR 1.60, 95% CI 1.31–1.94, p<0.001 in women and HR 1.15, 95% CI 1.02–1.29, p = 0.019 in men) and stroke (HR 1.26, 95% CI 1.13–1.40, p<0.001 in women and HR 1.19, 95% CI 1.09–1.30, p<0.001 in men).

Conclusions/Significance

Left ventricular mass has a graded and independent association with all-cause mortality, myocardial infarction and stroke.     

A Multicenter,Randomized, Controlled Trial of Osteopathic Manipulative Treatment on Preterms

BackgroundDespite some preliminary evidence, it is still largely unknown whether osteopathic manipulative treatment improves preterm clinical outcomes.ResultsA total of 695 newborns were randomly assigned to either the study group (n= 352) or the control group (n=343). A statistical significant difference was observed between the two groups for the primary outcome (13.8 and 17.5 days for the study and control group respectively, p<0.001, effect size: 0.31). Multivariate analysis showed a reduction of the length of stay of 3.9 days (95% CI -5.5 to -2.3, p<0.001). Furthermore, there were significant reductions with treatment as compared to usual care in cost (difference between study and control group: 1,586.01€; 95% CI 1,087.18 to 6,277.28; p<0.001) but not in daily weight gain. There were no complications associated to the intervention.ConclusionsOsteopathic treatment reduced significantly the number of days of hospitalization and is cost-effective on a large cohort of preterm infants.     

Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals

It is unclear if there is an association between the duration of delayed graft function (DGF) and kidney transplant (KT) outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412). Patients were grouped in quartiles according to duration of DGF (1–5, 6–10, 11–15, and >15 days, designated as prolonged DGF). The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064–4.184,p = 0.033) and more than 3 HLA mismatches (OR 1.819, CI95% 1.117–2.962,p = 0.016). The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001). Compared to patients without DGF, DGF(1–5), DGF(6–10), and DGF(11–15), patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003), graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001), death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001), and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001), respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270–6.618, p<0.001), death censored graft loss (OR 4.103, CI95% 2.055–8.193, p<0.001), and death (OR 3.065, CI95% 1.536–6.117, p = 0.001). Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year.     

GDF-15 for Prognostication of Cardiovascular and Cancer Morbidity and Mortality in Men

The objective was to evaluate the hypothesis that growth-differentiation factor 15 (GDF-15) is an independent marker of the long-term risk for both cardiovascular disease and cancer morbidity beyond clinical and biochemical risk factors. Plasma obtained at age 71 was available from 940 subjects in the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort. Complete mortality and morbidity data were obtained from public registries. At baseline there were independent associations between GDF-15 and current smoking, diabetes mellitus, biomarkers of cardiac (high-sensitivity troponin-T, NT-proBNP) and renal dysfunction (cystatin-C) and inflammatory activity (C-reactive protein), and previous cardiovascular disease (CVD). During 10 years follow-up there occurred 265 and 131 deaths, 115 and 46 cardiovascular deaths, and 185 and 86 events with coronary heart disease mortality or morbidity in the respective total cohort (n=940) and non-CVD (n=561) cohort. After adjustment for conventional cardiovascular risk factors, one SD increase in log GDF-15 were, in the respective total and non-CVD populations, associated with 48% (95%CI 26 to 73%, p<0.001) and 67% (95%CI 28 to 217%, p<0.001) incremental risk of cardiovascular mortality, 48% (95%CI 33 to 67%, p<0.001) and 61% (95%CI 38 to 89%, p<0.001) of total mortality and 36% (95%CI 19 to 56%, p<0.001) and 44% (95%CI 17 to 76%, p<0.001) of coronary heart disease morbidity and mortality. The corresponding incremental increase for cancer mortality in the respective total and non-cancer disease (n=882) population was 46% (95%CI 21 to 77%, p<0.001) and 38% (95%CI 12 to 70%, p<0.001) and for cancer morbidity and mortality in patients without previous cancer disease 30% (95%CI 12 to 51%, p<0.001). In conclusion, in elderly men, GDF-15 improves prognostication of both cardiovascular, cancer mortality and morbidity beyond established risk factors and biomarkers of cardiac, renal dysfunction and inflammation.