The utility of plasma glycated CD59 in predicting postpartum glucose intolerance: A prospective study of women diagnosed with GDM during a period of universal GDM screening.

AIMS: Gestational diabetes (GDM) is associated with the development of postpartum (PP) glucose intolerance. Plasma glycated CD59 (pGCD59) is an emerging biomarker for the detection of hyperglycaemia. The aim of this study was to assess the ability of PP pGCD59 to predict the development of PP GI as defined by the 2 h 75 g OGTT using the ADA criteria, in a cohort of women diagnosed with prior GDM in the index pregnancy using the 2 h 75 g OGTT at 24-28 weeks of gestation according to the World Health Organization (WHO) 2013 criteria. METHODS: Of the 2017 pregnant women recruited prospectively 140 women with gestational diabetes had samples for pGCD59 taken PP at the time of the OGTT. The ability of pGCD59 to predict the results of the PP OGTT was assessed using nonparametric receiver operating characteristic (ROC) curves. RESULTS: Women with PP glucose intolerance had significantly higher PP pGCD59 levels compared to women with normal glucose tolerance PP (3.8 vs. 2.7 SPU). PP pGCD59 identified women who developed glucose intolerance PP with an AUC of 0.80 (95% CI: 0.70-0.91). A PP pGCD59 cut-off value of 1.9 SPU generated a sensitivity of 100% (95% CI: 83.9-100), specificity of 16.9% (95% CI: 9.8-26.3), positive predictive value of 22.1% (95% CI: 21.0-22.6), and negative predictive value of 100% (95% CI: 87.4-100). PP fasting plasma glucose generated an AUC of 0.96 (95% CI: 0.89-0.99) for the identification of PP glucose intolerance. CONCLUSION: Our study found that PP pGCD9 may be a promising biomarker to identify women not requiring PP glucose intolerance screening using the traditional OGTT. While the diagnostic accuracy of pGCD59 is good, fasting plasma glucose remains a better test for the identification of PP glucose intolerance.

Diagnostic performance characteristics of planar quantitative and semi-quantitative parameters of Tc99m pyrophosphate (PYP) imaging for diagnosis of transthyretin (ATTR) cardiac amyloidosis: the SCAN-MP study.

BACKGROUND: The optimal heart-to-contralateral chest (H/CL) ratio threshold for non-invasive diagnosis of transthyretin cardiac amyloidosis (ATTR-CA) using Tc99m pyrophosphate (PYP) imaging in a population with low pretest probability is not known. METHODS: Using myocardial PYP retention by SPECT as the reference standard, we evaluated the diagnostic performance of different semi-quantitative and quantitative (H/CL chest ratio) planar parameters obtained from 3-hour PYP imaging in a prospectively recruited cohort of minority older adults with heart failure and increased LV wall thickness. RESULTS: Of 229 patients, 14 were found to have ATTR-CA (6.1%). No PYP uptake (grade 0) was observed in 77% of scans, all grade 3 scans were ATTR-CA, and only 4 of 11 (36%) grade 2 scans were ATTR-CA. An H/CL threshold of ≥ 1.4 maximized specificity (99%) and positive predictive value (93%) but resulted in decreased sensitivity (93%), compared to the ≥ 1.3 threshold which had 100% sensitivity. CONCLUSION: Among patients with a low pretest likelihood of ATTR-CA, planar interpretation, while useful to exclude disease, must be interpreted with caution. H/CL ratio threshold of ≥ 1.3 resulted in clinically important misclassifications. These data suggest that quantitative planar imaging thresholds may not be appropriate to apply in low pretest likelihood populations being evaluated for ATTR-CA.

Hypofractionated radiotherapy in postmastectomy locally advanced breast cancer: an interim report on acute toxicities and dosimetry.

Background: There is a growing interest in the use of hypofractionation in the setting of post-mastectomy radiation therapy (PMRT). Here, we present an interim report on the acute toxicities and the dosimetry of a 15-day hypofractionated regimen. Materials and methods: Patients aged 18-75 years who underwent mastectomy and had pathological stage IIB-IIIC or any clinical stage who had received neoadjuvant chemotherapy were treated with PMRT at a dose of 43.5 Gy in 15 fractions. Acute toxicities were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: Between September 2020 and September 2021, 92 patients were enrolled in the study. Majority experienced grade 1 dermatitis during the course of treatment. Skin toxicities peaked two weeks after PMRT in which 57 patients (62%) had grade 2 dermatitis and 6 patients (7%) had grade 3 dermatitis. Most resolved one month after treatment, with all resolving at three months. Grade 2 fatigue occurred in 4 patients (4%). There were no grade 3 fatigue or pneumonitis of any grade. The average V95% for the chest wall, axilla, and supraclavicular fossa were 91.5%, 99.3%, and 97.5%, respectively. Average ipsilateral lung V17 was 43.6%, while the mean heart dose averaged at 3.46 Gy. Conclusion: This interim report showed that hypofractionated PMRT is associated with a low incidence of clinically significant acute toxicities. With the use of the 3-dimensional conformal radiotherapy technique and volume-based planning, adequate target volume coverage and acceptable heart doses were achieved, although with a slightly higher ipsilateral lung dose.

Influence of Body Mass Index on Radiation Exposure Across Imaging Modalities in the Evaluation of Chest Pain.

BACKGROUND: Essential to a patient-centered approach to imaging individuals with chest pain is knowledge of differences in radiation effective dose across imaging modalities. Body mass index (BMI) is an important and underappreciated predictor of effective dose. This study evaluated the impact of BMI on estimated radiation exposure across imaging modalities. METHODS AND RESULTS: This was a retrospective analysis of patients with concern for cardiac ischemia undergoing positron emission tomography (PET)/computed tomography (CT), cadmium zinc telluride single-photon emission CT (SPECT) myocardial perfusion imaging, or coronary CT angiography (CCTA) using state-of-the-art imaging modalities and optimal radiation-sparing protocols. Radiation exposure was calculated across BMI categories based on established cardiac imaging-specific conversion factors. Among 9046 patients (mean±SD age, 64.3±13.1 years; 55% men; mean±SD BMI, 30.6±6.9 kg/m2), 4787 were imaged with PET/CT, 3092 were imaged with SPECT/CT, and 1167 were imaged with CCTA. Median (interquartile range) radiation effective doses were 4.4 (3.9-4.9) mSv for PET/CT, 4.9 (4.0-6.3) mSv for SPECT/CT, and 6.9 (4.0-11.2) mSv for CCTA. Patients at a BMI <20 kg/m2 had similar radiation effective dose with all 3 imaging modalities, whereas those with BMI ≥20 kg/m2 had the lowest effective dose with PET/CT. Radiation effective dose and variability increased dramatically with CCTA as BMI increased, and was 10 times higher in patients with BMI >45 kg/m2 compared with <20 kg/m2 (median, 26.9 versus 2.6 mSv). After multivariable adjustment, PET/CT offered the lowest effective dose, followed by SPECT/CT, and then CCTA (P<0.001). CONCLUSIONS: Although median radiation exposure is modest across state-of-the-art PET/CT, SPECT/CT, and CCTA systems using optimal radiation-sparing protocols, there are significant variations across modalities based on BMI. These data are important for making patient-centered decisions for ischemic testing.

Added prognostic value of visually estimated coronary artery calcium among heart transplant recipients.

BACKGROUND: Cardiac hybrid positron emission tomography/computed tomography (PET/CT) has become a valid screening modality for cardiac allograft vasculopathy (CAV) following heart transplantation (HT). Visually estimated coronary artery calcium (VECAC) can be quantified from CT images obtained as part of PET/CT and has been shown to be associated with adverse cardiovascular outcomes in coronary artery disease. We investigated the prognostic value of VECAC following HT. METHODS: A retrospective analysis of 430 consecutive adult HT patients who underwent 13N-ammonia cardiac PET/CT from 2016 to 2019 with follow-up through October 15, 2022, was performed. VECAC categories included: VECAC 0, VECAC 1-9, VECAC 10-99, and VECAC 100+. The association between VECAC categories and outcomes was assessed using univariable and multivariable proportional hazards regression. The primary outcome was death/retransplantation. RESULTS: The cohort was 73% male, 33% had diabetes, 67% had estimated glomerular filtration rate <60 ml/min, median age was 61 years, and median time since HT was 7.5 years. VECAC alone was insufficiently sensitive to screen for CAV. During a median follow-up of 4.2 years ninety patients experienced death or retransplantation. Compared with those with VECAC 0, patients VECAC 10-99 (HR 2.25, 95% CI 1.23-4.14, p = 0.009) and VECAC 100+ (HR 3.42, 95% CI 1.96-5.99, p < 0.001) experienced an increased risk of death/retransplantation. The association was similar for cardiovascular death and cardiovascular hospitalization. After adjusting for other predictors of death/retransplantation, VECAC 10-99 (VECAC 10-99: aHR 1.95, 95% CI 1.03-3.71 p = 0.04) and VECAC 100+ (VECAC 100+: aHR 2.33, 95% CI 1.17-4.63, p = 0.02) remained independently associated with death/retransplantation. CONCLUSIONS: VECAC is an independent prognostic marker of death/retransplantation following HT and merits inclusion as a part of post-HT surveillance PET/CT.

Impact of cardiac size on diagnostic performance of single-photon emission computed tomography myocardial perfusion imaging: insights from the REgistry of Fast Myocardial Perfusion Imaging with NExt generation single-photon emission computed tomography.

AIMS: Variation in diagnostic performance of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been observed, yet the impact of cardiac size has not been well characterized. We assessed whether low left ventricular volume influences SPECT MPI's ability to detect obstructive coronary artery disease (CAD) and its interaction with age and sex. METHODS AND RESULTS: A total of 2066 patients without known CAD (67% male, 64.7 ± 11.2 years) across nine institutions underwent SPECT MPI with solid-state scanners followed by coronary angiography as part of the REgistry of Fast Myocardial Perfusion Imaging with NExt Generation SPECT. Area under receiver-operating characteristic curve (AUC) analyses evaluated the performance of quantitative and visual assessments according to cardiac size [end-diastolic volume (EDV); <20th vs. ≥20th population or sex-specific percentiles], age (<75 vs. ≥75 years), and sex. Significantly decreased performance was observed in patients with low EDV compared with those without (AUC: population 0.72 vs. 0.78, P = 0.03; sex-specific 0.72 vs. 0.79, P = 0.01) and elderly patients compared with younger patients (AUC 0.72 vs. 0.78, P = 0.03), whereas males and females demonstrated similar AUC (0.77 vs. 0.76, P = 0.67). The reduction in accuracy attributed to lower volumes was primarily observed in males (sex-specific threshold: EDV 0.69 vs. 0.79, P = 0.01). Accordingly, a significant decrease in AUC, sensitivity, specificity, and negative predictive value for quantitative and visual assessments was noted in patients with at least two characteristics of low EDV, elderly age, or male sex. CONCLUSION: Detection of CAD with SPECT MPI is negatively impacted by small cardiac size, most notably in elderly and male patients.

The ability of pGCD59 to predict adverse pregnancy outcomes: a prospective study of non-diabetic pregnant women in Ireland.

AIM: Even though most pregnancies are uneventful, occasionally complications do occur. Gestational diabetes is linked to an increased risk of adverse pregnancy outcomes. Early identification of women at risk of experiencing adverse outcomes, ideally through a single blood test, would facilitate early intervention. Plasma glycated CD59 (pGCD59) is an emerging biomarker which has shown promise in identifying hyperglycaemia during pregnancy and has been associated with the risk of delivering an LGA infant. The aim of this study was to explore the ability of the first- and second-trimester pGCD59 to predict adverse pregnancy outcomes. METHODS: This was a prospective study of 378 pregnant women. Samples for pGCD59 were taken at the first antenatal visit and at the time of the 2 h 75 g OGTT (24-28 weeks of gestation). Adjusted receiver operating characteristic curves were used to evaluate the ability of pGCD59 to predict maternal and neonatal outcomes. RESULTS: First-trimester pGCD59 levels were higher in women with gestational diabetes who delivered a macrosomic infant (4.2 ± 0.7 vs. 3.5 ± 1.0 SPU, p < 0.01) or an LGA infant (4.3 ± 0.3 vs. 3.6 ± 1.0 SPU, p = 0.01) compared to women with GDM that did not experience these outcomes. Second-trimester pGCD59 levels were higher in women that developed polyhydramnios (2.9 ± 0.4 vs. 2.5 ± 1.1 SPU, p = 0.03). First- and second-trimester pGCD59 predicted pregnancy-induced hypertension with good accuracy (AUC:0.85, 95%CI:0.78-0.91; AUC: 0.80, 95%CI: 0.73-0.88, respectively) and neonatal hypoglycaemia with fair to good accuracy (AUC:0.77, 95%CI: 0.54-0.99, AUC:0.81, 95%CI:0.62-0.99). CONCLUSIONS: This study has shown that pGCD59 has the potential to predict adverse pregnancy outcomes. Prospective studies with a larger number of cases are necessary to fully explore and validate the potential of this emerging biomarker in predicting adverse pregnancy outcomes.

Absence of long-term structural and functional cardiac abnormalities on multimodality imaging in a multi-ethnic group of COVID-19 survivors from the early stage of the pandemic.

Aims: Many patients with coronavirus disease-2019 (COVID-19), particularly from the pandemic's early phase, have been reported to have evidence of cardiac injury such as cardiac symptoms, troponinaemia, or imaging or ECG abnormalities during their acute course. Cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) have been widely used to assess cardiac function and structure and characterize myocardial tissue during COVID-19 with report of numerous abnormalities. Overall, findings have varied, and long-term impact of COVID-19 on the heart needs further elucidation. Methods and results: We performed TTE and 3 T CMR in survivors of the initial stage of the pandemic without pre-existing cardiac disease and matched controls at long-term follow-up a median of 308 days after initial infection. Study population consisted of 40 COVID-19 survivors (50% female, 28% Black, and 48% Hispanic) and 12 controls of similar age, sex, and race-ethnicity distribution; 35% had been hospitalized with 28% intubated. We found no difference in echocardiographic characteristics including measures of left and right ventricular structure and systolic function, valvular abnormalities, or diastolic function. Using CMR, we also found no differences in measures of left and right ventricular structure and function and additionally found no significant differences in parameters of tissue structure including T1, T2, extracellular volume mapping, and late gadolinium enhancement. With analysis stratified by patient hospitalization status as an indicator of COVID-19 severity, no differences were uncovered. Conclusion: Multimodal imaging of a diverse cohort of COVID-19 survivors indicated no long-lasting damage or inflammation of the myocardium.

Assessment of the prevalence of pain, adequacy of pain management and influencing factors in patients undergoing radiotherapy.

Pain is prevalent among patients with cancer who are being treated with radiotherapy. However, the prevalence of pain varies across regions, and pain management is affected by several factors. This cross-sectional study aims to determine the prevalence of pain, assess the adequacy of pain management and identify factors affecting pain in patients undergoing radiotherapy. A total of 94 patients were included in the study. The prevalence of pain was determined through the Brief Pain Inventory tool, while the adequacy of pain management was assessed through the Pain Management Index. Demographic, clinical and treatment-related factors were obtained and analysed for association with the presence of pain and the adequacy of pain management. Of the 94 patients, 59 (62.8%) experienced pain while 35 (47.2%) did not. The mean pain intensity score of patients was 3.6 (standard deviation: 2.3). Most patients (67.8%) experienced mild pain with low pain interference (67.8%) on daily functions. Of the 59 patients who experienced pain, 34 (57.6%) had inadequate pain relief while 25 (42.2%) had adequate pain control. Being admitted at the hospital during radiotherapy was significantly associated with adequate pain relief. Use of analgesic was also significantly associated with pain management, with a higher rate of weak and strong opioid use in those with adequately treated pain. In this single-institution study, the prevalence of pain was high. Pain management was inadequate in more than half of the patients experiencing pain. A disparity in the prescription of analgesics, particularly opioids, was observed. Patients with inadequate pain management were less likely to receive opioids, which likely reflects the presence of several barriers that limit its access to patients.

Practice Patterns in Surgical Neuro-Oncology Among Low- and Middle-Income Countries During the Coronavirus Disease 2019 Pandemic: A Scoping Review and Situational Report from the Philippines.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has negatively affected the outcomes of surgical neuro-oncology patients worldwide. We aimed to review the practice patterns in surgical neuro-oncology in low- and middle-income countries (LMICs). We also present a situational report from our own country. METHODS: A scoping review was performed following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. RESULTS: Twelve studies were included in the review. Most of the studies were from Asia (India, China, Iran, and Turkey), and 1 was from Brazil. Quantitative reports showed a decrease in the number of surgical neuro-oncology operations between pre-COVID-19 and post-COVID-19 time frames, but similar proportions of neuro-oncology procedures. Qualitative review showed similar practice patterns between LMICs and high-income countries, except for limitations in resources such as negative-pressure operating rooms and intensive care units, and maintenance of face-to-face consults despite the adoption of telemedicine. Limited data on adjuvant therapy were available in LMICs. CONCLUSIONS: In our review, we found that the practice patterns in surgical neuro-oncology in LMICs during the COVID-19 pandemic are similar to those in high-income countries, except for a few modifications because of resource limitation and patient preferences.

The utility of first trimester plasma glycated CD59 (pGCD59) in predicting gestational diabetes mellitus: A prospective study of non-diabetic pregnant women in Ireland.

AIMS: To evaluate the ability of first trimester plasma glycated CD59 (pGCD59) to predict gestational diabetes mellitus (GDM) at 24-28 weeks of gestation. METHODS: Prospectively, in 378 pregnant women, GDM was diagnosed using the one step 2 h 75 g oral glucose tolerance test adjudicated by the World Health Organisation (WHO) 2013 criteria. The ability of pGCD59 to predict GDM was assessed using receiver operating characteristic (ROC) curves adjusted for maternal age, body mass index (BMI), maternal ethnicity, parity, previous GDM, family history of diabetes mellitus and week of gestation at time of pGCD59 sampling. RESULTS: pGCD59 generated an adjusted area under the curve (AUC) of (a) 0.63 (95 %CI:0.56-0.70, p < 0.001) for predicting GDM, and (b) 0.71 (95 %CI:0.62-0.79, p < 0.001 for GDM diagnosed with a fasting plasma glucose (FPG) ≥ 5.1 mmol/L. Sensitivity analysis of BMI subgroups showed that pGCD59 generated the highest AUC in the 35 kg/m2 ≤ BMI < 40 kg/m2 (AUC:0.85, 95 %CI:0.70-0.98) and BMI ≥ 40 kg/m2 (AUC:0.88, 95 %CI:0.63-0.99) categories. CONCLUSIONS: Early in pregnancy, pGCD59 may be a good predictor of GDM in women with a high BMI and a fair predictor of GDM diagnosed by an elevated FPG independent of BMI.

The Diagnostic Accuracy of Second Trimester Plasma Glycated CD59 (pGCD59) to Identify Women with Gestational Diabetes Mellitus Based on the 75 g OGTT Using the WHO Criteria: A Prospective Study of Non-Diabetic Pregnant Women in Ireland.

The aim of this study was to evaluate the ability of second trimester plasma glycated CD59 (pGCD59), a novel biomarker, to predict the results of the 2 h 75 g oral glucose tolerance test at 24−28 weeks of gestation, employing the 2013 World Health Organisation criteria. This was a prospective study of 378 pregnant women. The ability of pGCD59 to predict gestational diabetes (GDM) was assessed using adjusted ROC curves for maternal age, BMI, maternal ethnicity, parity, previous GDM, and family history of diabetes. The pGCD59 levels were significantly higher in women with GDM compared to women with normal glucose tolerance (p = 0.003). The pGCD59 generated an adjusted AUC for identifying GDM cases of 0.65 (95%CI: 0.58−0.71, p < 0.001). The pGCD59 predicted GDM status diagnosed by a fasting glucose value of 5.1 mmol/L with an adjusted AUC of 0.74 (95%CI: 0.65−0.81, p < 0.001). Analysis of BMI subgroups determined that pGCD59 generated the highest AUC in the 35 kg/m2 ≤ BMI < 40 kg/m2 (AUC: 0.84 95%CI: 0.69−0.98) and BMI ≥ 40 kg/m2 (AUC: 0.96 95%CI: 0.86−0.99) categories. This study found that second trimester pGCD59 is a fair predictor of GDM status diagnosed by elevated fasting glucose independent of BMI and an excellent predictor of GDM in subjects with a very high BMI.

The Role of Early Pregnancy Maternal pGCD59 Levels in Predicting Neonatal Hypoglycemia-Subanalysis of the DALI Study.

CONTEXT: Neonatal hypoglycaemia (NH) is the most common metabolic problem in infants born of mothers with gestational diabetes. Plasma glycated CD59 (pGCD59) is an emerging biomarker that has shown potential in identifying women at risk of developing gestational diabetes. The aim of this study was to assess the association between early maternal levels of pGCD59 and NH. OBJECTIVE: The aim of this study was to assess the association between early pregnancy maternal levels of plasma glycated CD59 (pGCD59) and neonatal hypoglycemia (NH). METHODS: This is an observational study of pregnant women with a prepregnancy body mass index (BMI) greater than or equal to 29 screened for eligibility to participate in the Vitamin D and Lifestyle Intervention for Gestational Diabetes (DALI) trial. This analysis included 399 pregnancies. Levels of pGCD59 were measured in fasting maternal samples taken at the time of a 75-g, 2-hour oral glucose tolerance test performed in early pregnancy (< 20 weeks). NH, the study outcome, was defined as a heel-prick capillary glucose level of less than 2.6 mmol/L within 48 hours of delivery. RESULTS: We identified 30 infants with NH. Maternal levels of pGCD59 in early pregnancy were positively associated with the prevalence of NH (one-way analysis of variance, P < .001). The odds of NH were higher in infants from mothers in tertile 3 of pGCD59 levels compared to those from mothers in tertile 1 (odds ratio [OR]: 2.41; 95% CI, 1.03-5.63). However, this was attenuated when adjusted for maternal BMI (OR: 2.28; 95% CI, 0.96-5.43). The cross-validated area under the curve (AUC) was 0.64 (95% CI, 0.54-0.74), and adjusted for maternal BMI, age, and ethnicity, the AUC was 0.70 (95% CI, 0.56-0.78). CONCLUSION: Although pGCD59 levels in early pregnancy in women with BMI greater than or equal to 29 are associated with NH, our results indicate that this biomarker by itself is only a fair predictor of NH.

Plasma-glycated CD59 as an early biomarker for gestational diabetes mellitus: prospective cohort study protocol.

INTRODUCTION: The significant maternal and neonatal outcomes of gestational diabetes mellitus (GDM) make it a major public health concern. Mothers with GDM are at greater risk of pregnancy complications and their offspring are at higher risk of diabetes and obesity. Currently, GDM is diagnosed with glucose load methods which are time-consuming and inconvenient to administer more than once during pregnancy; for this reason, there is a recognised need for a more accurate and simpler test for GDM. Previous studies indicate that plasma-glycated CD59 (pGCD59) is a novel biomarker for GDM. We present here the protocol of a prospective cohort study designed to (1) determine the accuracy of pGCD59 as an early, first trimester predictor of GDM and gestational impaired glucose tolerance and (2) assess the associations between pGCD59 levels and adverse maternal and neonatal outcomes. METHODS AND ANALYSIS: We will obtain discarded plasma samples from pregnant women at two time points: first prenatal visit (usually <14 weeks gestation) and gestational weeks 24-28. A study-specific medical record abstraction tool will be used to obtain relevant maternal and neonatal clinical data from the EPIC clinical database. The prevalence of GDM will be determined using standard of care glucose load test results. We will determine the sensitivity and specificity of pGCD59 to predict the diagnosis of GDM and gestational impaired glucose tolerance, as well as the associations between levels of pGCD59 and the prevalence of maternal and neonatal outcomes. ETHICS AND DISSEMINATION: This study has been approved by the Mass General Brigham Institutional Review Board (protocol 2011P002254). The results of this study will be presented at international meetings and disseminated in peer-reviewed journals.

Noninvasive Physiologic Assessment of Cardiac Allograft Vasculopathy Is Prognostic for Post-Transplant Events.

BACKGROUND: Cardiac allograft vasculopathy (CAV) causes impaired blood flow in both epicardial coronary arteries and the microvasculature. A leading cause of post-transplant mortality, CAV affects 50% of heart transplant recipients within 10 years of heart transplant. OBJECTIVES: This analysis examined the outcomes of heart transplant recipients with reduced myocardial blood flow reserve (MBFR) and microvascular CAV detected by 13N-ammonia positron emission tomography (PET) myocardial perfusion imaging. METHODS: A total of 181 heart transplant recipients who underwent PET to assess for CAV were included with a median follow-up of 4.7 years. Patients were classified into 2 groups according to the total MBFR: >2.0 and ≤2.0. Microvascular CAV was defined as no epicardial CAV detected by PET and/or coronary angiography, but with an MBFR ≤2.0 by PET. RESULTS: In total, 71 (39%) patients had an MBFR ≤2.0. Patients with an MBFR ≤2.0 experienced an increased risk for all outcomes: 7-fold increase in death or retransplantation (HR: 7.05; 95% CI: 3.2-15.6; P < 0.0001), 12-fold increase in cardiovascular death (HR: 12.0; 95% CI: 2.64-54.12; P = 0.001), and 10-fold increase in cardiovascular hospitalization (HR: 10.1; 95% CI: 3.43-29.9; P < 0.0001). The 5-year mean survival was 302 days less than those with an MBFR >2.0 (95% CI: 260.2-345.4 days; P < 0.0001). Microvascular CAV (adjusted HR: 3.86; 95% CI: 1.58-9.40; P = 0.003) was independently associated with an increased risk of death or retransplantation. CONCLUSIONS: Abnormal myocardial blood flow reserve, even in the absence of epicardial CAV, identifies patients at a high risk of death or retransplantation. Measures of myocardial blood flow provide prognostic information in addition to traditional CAV assessment.

The endothelial protein C receptor plays an essential role in the maintenance of pregnancy.

Placenta-mediated pregnancy complications are a major challenge in the management of maternal-fetal health. Maternal thrombophilia is a suspected risk factor, but the role of thrombotic processes in these complications has remained unclear. Endothelial protein C receptor (EPCR) is an anticoagulant protein highly expressed in the placenta. EPCR autoantibodies and gene variants are associated with poor pregnancy outcomes. In mice, fetal EPCR deficiency results in placental failure and in utero death. We show that inhibition of molecules involved in thrombin generation or in the activation of maternal platelets allows placental development and embryonic survival. Nonetheless, placentae exhibit venous thrombosis in uteroplacental circulation associated with neonatal death. In contrast, maternal EPCR deficiency results in clinical and histological features of placental abruption and is ameliorated with concomitant Par4 deficiency. Our findings unveil a causal link between maternal thrombophilia, uterine hemorrhage, and placental abruption and identify Par4 as a potential target of therapeutic intervention.

Maintaining extraembryonic expression allows generation of mice with severe tissue factor pathway inhibitor deficiency.

Tissue factor pathway inhibitor (TFPI) is a serine protease with multiple anticoagulant activities. The Kunitz1 (K1) domain of TFPI binds the active site of factor VIIa and is required for inhibition of tissue factor (TF)/factor VIIa catalytic activity. Mice lacking TFPI K1 domain die in utero. TFPI is highly expressed on trophoblast cells of the placenta. We used genetic strategies to selectively ablate exon 4 encoding TFPI K1 domain in the embryo, while maintaining expression in trophoblast cells. This approach resulted in expected Mendelian frequency of TFPI K1 domain-deficient mice. Real-time polymerase chain reaction confirmed 95% to 99% genetic deletion and a similar reduction in transcript expression. Western blotting confirmed the presence of a truncated protein instead of full-length TFPI. Mice with severe TFPI K1 deficiency exhibited elevated thrombin-antithrombin (TAT) levels, frequent fibrin deposition in renal medulla, and increased susceptibility to TF-induced pulmonary embolism. They were fertile, and most lived normal life spans without any overt thrombotic events. Of 43 mice observed, 2 displayed extensive brain ischemia and infarction. We conclude that in contrast to complete absence of TFPI K1 domain, severe deficiency is compatible with in utero development, adult survival, and reproductive functions in mice. Inhibition of TFPI activity is being evaluated as a means of boosting thrombin generation in hemophilia patients. Our results show that in mice severe reduction of TFPI K1 activity is associated with a prothrombotic state without overt developmental outcomes. We note fibrin deposits in the kidney and rare cases of brain ischemia.

Prevalencia de caries de infancia temprana severa y factores de riesgo asociados en un grupo de niños del área metropolitana de Guatemala / Prevalência de cárie precoce na infância e fatores de risco associados em um grupo de crianças na região metropolitana da Guatemala / Prevalence of severe early childhood caries and associated risk factors in a group of children in the metropolitan area of Guatemala

Objetivo: Determinar la prevalencia y severidad de caries de infancia temprana severa y factores de riesgo asociados en una poblaciónn de niños de 6-36 meses de edad, que asisten a guarderías estatales del área metropolitana de la ciudad de Guatemala. Materiales y métodos: Diseño analítico transversal. Se examinaron clínicamente 110 niños de 13 a 36 meses de edad para determinar el estado de caries según los criterios del Sistema Internacional de Detección y Valoración de Caries (Kappa 0.69). Además, se determinaron las características sociodemográficas, hábitos de alimentación e higiene dental a través de una entrevista a las madres de los participantes y se realizó análisis descriptivo de estas variables. Para determinar la relación entre variables se aplicaron las pruebas estadísticas U de Man Whitney y Tau-b de Kendall. Resultados: Se encontró una prevalencia de caries de infancia temprana severa de 81.8%. En promedio cada individuo presentó 6.74 lesiones cariosas (IC 95% 5.62 - 7.92). El número promedio de lesiones no cavitadas fue 6.06 y de lesiones cavitadas fue 2.51. Se encontró que la edad y el porcentaje de superficies dentarias con presencia de placa están significativamente asociados con las caries de infancia temprana severa. Conclusiones: La alta prevalencia de caries (81.8%) y el carácter reversible de 2/3 de las lesiones encontradas demanda intervenciones preventivas de salud dental en esta población.

Objetivo: Determinar a prevalência e a gravidade de cáries precoce na infância e fatores de risco associados em uma população de crianças de 6 a 36 meses que frequentam creches estaduais na região metropolitana da Cidade da Guatemala.Material e métodos: Projeto analítico transversal 110 crianças de 13 a 36 meses de idade foram examinadas clinicamente para determinar o status de cárie de acordo com os critérios do Sistema Internacional de Detecção e Avaliação de Cárie (Kappa 0,69). Além disso, as características sociodemográficas, hábitos alimentares e higiene dental foram determinadas por meio de entrevista com as mães dos participantes e análise descritiva dessas variáveis. Para determinar a relação entre as variáveis, foram aplicados os testes estatísticos U de Man Whitney e Tau-b de Kendall. Resultados: A prevalência de cárie na primeira infância foi de 81,8%. Em média, cada indivíduo apresentou 6,74 lesões de cárie (IC95 % 5,62 - 7,92). O número médio de lesões não cavitadas foi de 6,06 e as cavitadas foram de 2,51. Verificou-se que a idade e a porcentagem de superfícies dentárias com presença de placa estão significativamente associadas à cárie precoce. Conclusões: A alta prevalência de cárie encontrada (81,8 %) e do tipo reversível foi de 2/3 das lesões encontradas demandam intervenções preventivas de saúde bucal nessa população

Objective: To determine the prevalence and severity of early childhood caries and the associated risk factors, in a population of 6 to 36 months old children that attend governmental daycares in the metropolitan area of Guatemala City. Methods: Cross-sectional analytical design 110 children from 13 to 36 months of age were clinically examined to determine caries status according to the criteria of the International Caries Detection and Assessment System (Kappa 0.69). In addition, sociodemographic characteristics, eating and dental hygiene habits were established through a survey done to the mothers of the participants. To determine the relationship between variables, the statistical tests U of Man Whitney and Tau-b of Kendall were applied. Results: There was an 81.8% of prevalence found of severe early childhood caries. In average, each subject showed 6.74 carious lesions (IC 95% 5.62 ­ 7.92). The average number of non-cavitated lesions was 6.06 and 2.51 for cavitated lesions. It was found that age (τb = .224, p = .001) and the percentage of dental surface with plaque (τb = 0.352 p = .002) are significantly associated with severe early childhood caries. Conclusion: The high prevalence from found caries (81.8%) and the reversible type of 2/3 from the found lesions, show a need of preventive interventions of dental health in this population