Structural racism is a mediator of disparities in acute myeloid leukemia outcomes.

Non-Hispanic Black (NHB) and Hispanic patients with acute myeloid leukemia (AML) have higher mortality rates than non-Hispanic White (NHW) patients despite more favorable genetics and younger age. A discrete survival analysis was performed on 822 adult patients with AML from 6 urban cancer centers and revealed inferior survival among NHB (hazard ratio [HR] = 1.59; 95% confidence interval [CI]: 1.15, 2.22) and Hispanic (HR = 1.25; 95% CI: 0.88, 1.79) patients compared with NHW patients. A multilevel analysis of disparities was then conducted to investigate the contribution of neighborhood measures of structural racism on racial/ethnic differences in survival. Census tract disadvantage and affluence scores were individually calculated. Mediation analysis of hazard of leukemia death between groups was examined across 6 composite variables: structural racism (census tract disadvantage, affluence, and segregation), tumor biology (European Leukemia Network risk and secondary leukemia), health care access (insurance and clinical trial enrollment), comorbidities, treatment patterns (induction intensity and transplant utilization), and intensive care unit (ICU) admission during induction chemotherapy. Strikingly, census tract measures accounted for nearly all of the NHB-NHW and Hispanic-NHW disparity in leukemia death. Treatment patterns, including induction intensity and allogeneic transplant, and treatment complications, as assessed by ICU admission during induction chemotherapy, were additional mediators of survival disparities in AML. This is the first study to formally test mediators for observed disparities in AML survival and highlights the need to investigate the mechanisms by which structural racism interacts with known prognostic and treatment factors to influence leukemia outcomes.

Interventional pharmacoeconomics for immune checkpoint inhibitors through alternative dosing strategies.

Immune checkpoint inhibitors (ICIs) are approved for the treatment of a variety of cancer types. The doses of these drugs, though approved by the Food and Drug Administration (FDA), have never been optimised, likely leading to significantly higher doses than required for optimal efficacy. Dose optimisation would hypothetically decrease the risk, severity, and duration of immune-related adverse events, as well as provide an opportunity to reduce costs through interventional pharmacoeconomic strategies such as off-label dose reductions or less frequent dosing. We summarise existing evidence for ICI dose optimisation to advocate for the role of interventional pharmacoeconomics.

Quantitative thoracic aorta calcification assessment by 18F-NaF PET/CT and its correlation with atherosclerotic cardiovascular disorders and increasing age.

OBJECTIVES: We aimed to assess the correlation between age and cardiovascular risk factors with NaF-PET/CT imaging in the thoracic aorta (TA). METHODS: In this prospective study, 80 healthy controls and 44 patients with chest pain underwent NaF-PET/CT imaging, and three segments of the aorta (ascending, arch, and descending) were examined. Average SUVmax, SUVmean, and Alavi-Carlsen Score (ACS) were calculated in each segment and the entire vessel. The degree of NaF uptake in controls and patients and its correlation with age were determined. Multivariate linear regression and logistic regression models were employed to determine the predictabilities of Framingham Risk Score (FRS) and unfavorable cardiovascular disease (CVD) risk profile by these measurements. RESULTS: Average SUVmax, average SUVmean, and ACS were significantly higher in patients than in controls, and all correlated well with age. The correlation of average SUVmean with age was significant in both controls (r = 0.32, p = 0.04) and patients (r = 0.64, p < 0.001). ACS of the entire TA was a stronger predictor of FRS compared with average SUVmax and average SUVmean (adjusted R2 = 0.38, standardized ß = 0.58, p < 0.001). ACS was a significant predictor of unfavorable CVD risk profile as compared with other values (odds ratio = 1.006, 95% CI = 1.000-1.013, p = 0.05). CONCLUSIONS: Active calcification in TA correlates with age, and its correlation is higher among subjects with CVD risk factors. Global assessment (ACS) can predict unfavorable CVD risk profile. These data provide evidence for the potential role of NaF in assessing micro-calcification in arteries and its relations to cardiovascular events. KEY POINTS: • Global micro-calcification in the thoracic aorta as measured by NaF-PET/CT imaging correlates with increasing age. • The extent of the correlation was higher among patients with cardiovascular disease (CVD) risk factors. • These data provide evidence for the potential role of NaF in assessing active calcification in arteries and its relations to cardiovascular events.

Diagnostic accuracy of the PLASMIC score in patients with suspected thrombotic thrombocytopenic purpura: A systematic review and meta-analysis.

BACKGROUND: The PLASMIC score was developed to identify patients with thrombotic microangiopathy who are most likely to have immune thrombotic thrombocytopenic purpura (TTP) and benefit from therapeutic plasma exchange (TPE). PLASMIC scores of 0-4, 5, and 6-7 are said to correspond to low, intermediate, and high probability of TTP, respectively. STUDY DESIGN AND METHODS: We conducted a systematic review and meta-analysis on the diagnostic accuracy of the PLASMIC score in adults with suspected TTP. We evaluated the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of PLASMIC score thresholds of ≥5 and ≥6. Study quality was appraised using the QUADAS-2 tool. RESULTS: We identified 13 eligible studies, which collectively enrolled 970 patients. The median prevalence of TTP among eligible studies was 35%. The sensitivity and specificity of a PLASMIC score ≥5 was 0.99 (95% confidence interval [CI], 0.91-1.00) and 0.57 (95% CI, 0.41-0.72), respectively. At a prevalence of 35%, the NPV of a PLASMIC score ≥5 was 0.99 (95% CI, 0.92-1.00). A PLASMIC score ≥6 was associated with a sensitivity and specificity of 0.85 (95% CI, 0.67-0.94) and 0.89 (95% CI, 0.81-0.94), respectively. The NPV of a PLASMIC score ≥6 at a prevalence of 35% was 0.92 (95% CI, 0.82-0.97). CONCLUSION: A PLASMIC score threshold of ≥5 is associated with high sensitivity and NPV and may be a useful screening tool for identifying patients who are unlikely to have TTP and do not require TPE, though prospective assessment is required. A PLASMIC score <6 appears to have insufficient sensitivity to rule out TTP and the need for TPE.

18F-NaF and 18F-FDG as molecular probes in the evaluation of atherosclerosis.

The early detection of atherosclerotic disease is vital to the effective prevention and management of life-threatening cardiovascular events such as myocardial infarctions and cerebrovascular accidents. Given the potential for positron emission tomography (PET) to visualize atherosclerosis earlier in the disease process than anatomic imaging modalities such as computed tomography (CT), this application of PET imaging has been the focus of intense scientific inquiry. Although 18F-FDG has historically been the most widely studied PET radiotracer in this domain, there is a growing body of evidence that 18F-NaF holds significant diagnostic and prognostic value as well. In this article, we review the existing literature on the application of 18F-FDG and 18F-NaF as PET probes in atherosclerosis and present the findings of original animal and human studies that have examined how well 18F-NaF uptake correlates with vascular calcification and cardiovascular risk.

Normal patterns of regional brain 18F-FDG uptake in normal aging.

OBJECTIVE: Normal aging alters the brain function even in the absence of recognizable structural changes, which can be detected using modern in vivo functional imaging modalities such as fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET) scan. It is highly important to recognize normal age-dependent changes in order to correctly diagnose pathologic states. The goal of the current study was to evaluate the age-related changes in regional brain 18F-FDG uptake in normal healthy population. SUBJECTS AND METHODS: This study was part of the cardiovascular molecular calcification assessed by 18F-sodium fluoride (NaF) (CAMONA) PET/computed tomography (CT) study. This study was approved by the Danish National Committee on Health Research Ethics registered at ClinicalTrials.gov (NCT01724749). Forty normal healthy subjects were prospectively recruited in group A (22-32 years) and B (56-75 years) and underwent 18F-FDG PET/CT. Static images were obtained 180 minutes following 18F-FDG injection. Supratentorial (including individual measurements for frontal, parieto-occipital and temporal lobes) and cerebellar 18F-FDG uptakes were measured by manual placement of region of interest (ROI) over these regions based on predefined criteria for each and standardized uptake value (SUVmean) values were calculated using OsiriX software. RESULTS: The mean ages of the patients in group A was 26.1±3.4 versus 61±4.4 for group B. There were 10 females in group A and 10 females in group B. Mean SUV of cerebellum was 6.80±1.21 for the young subjects compared to 6.08±0.7 among old subjects (independent t-test, P=0.028). Mean SUV of supratentorial brain was 9.14±1.83 for the young subjects compared to 6.92±072 among old subjects (P<0.001). Mean SUV of frontal (9.72±1.97 vs. 7.03±0.69), temporal (7.37±1.52 vs. 5.65±0.68) and parieto-occipital region (10.7±2.28 vs. 7.41±0.79) was higher among young patients (P<0.001). More interestingly, SUVmean of supratentorial brain was significantly higher among female healthy volunteers in both groups (P= 0.025 and 0.047 for group A and B, respectively). CONCLUSION: In conclusion, these findings confirm a significant age dependent reduction of supratentorial 18F-FDG uptake among healthy individuals. However, cerebellum 18F-FDG uptake reduction was not so redundant. Fluorine-18-FDG uptake of all cerebral lobes including frontal, parieto-occipital and temporal decreases with normal aging in a same fashion. Interestingly, among both young and old female subjects, higher uptake was seen in supratentorial brain.

An update on the role of PET/CT and PET/MRI in ovarian cancer.

This review article summarizes the role of PET/CT and PET/MRI in ovarian cancer. With regard to the diagnosis of ovarian cancer, the presence of FDG uptake within the ovary of a postmenopausal woman raises the concern for ovarian cancer. Multiple studies show that FDG PET/CT can detect lymph node and distant metastasis in ovarian cancer with high accuracy and may, therefore, alter the management to obtain better clinical outcomes. Although PET/CT staging is superior for N and M staging of ovarian cancer, its role is limited for T staging. Additionally, FDG PET/CT is of great benefit in evaluating treatment response and has prognostic value in patients with ovarian cancer. FDG PET/CT also has value to detect recurrent disease, particularly in patients with elevated serum CA-125 levels and negative or inconclusive conventional imaging test results. PET/MRI may beneficial for tumor staging because MRI has higher soft tissue contrast and no ionizing radiation exposure compared to CT. Some non-FDG PET radiotracers such as 18F-fluorothymidine (FLT) or 11C-methionine (MET) have been studied in preclinical and clinical studies as well and may play a role in the evaluation of patients with ovarian cancer.

Riluzole in augmentation of fluvoxamine for moderate to severe obsessive-compulsive disorder: Randomized, double-blind, placebo-controlled study.

AIM: The aim of the present randomized, double-blind, placebo-controlled, 8-week trial was to assess the efficacy and tolerability of riluzole augmentation of fluvoxamine in treatment of patients with moderate to severe obsessive-compulsive disorder. METHODS: Patients were randomized into two parallel groups to receive fluvoxamine plus placebo or fluvoxamine plus riluzole (50 mg twice daily). All patients, regardless of their treatment group, received fluvoxamine at 100 mg/day for the initial 4 weeks of the study followed by 200 mg/day of fluvoxamine for the rest of the trial course. A total of 50 patients (25 in each group) were evaluated for response to treatment using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) at baseline and at weeks 4, 8 and 10. Side-effects were recorded using predesigned checklists in each visit. Repeated-measure analysis of variance showed a significant effect for time × treatment interaction in the Y-BOCS total score and a significant effect for time × treatment interaction in the Y-BOCS Compulsive subscale score between the two groups. RESULTS: Repeated-measure analysis of variance showed a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 4.07, d.f. = 1.22, P = 0.04) in the Y-BOCS total score and a significant effect for time × treatment interaction (Greenhouse-Geisser corrected: F = 4.45, d.f. = 1.33, P = 0.028) in the Y-BOCS Compulsive subscale score between the two groups. Riluzole augmentation therapy demonstrated higher, partial or complete treatment response according to the Y-BOCS total scores. CONCLUSION: Riluzole may be of clinical use as an adjuvant agent to fluvoxamine in treatment of moderate to severe obsessive-compulsive disorder.

Update of the role of PET/CT and PET/MRI in the management of patients with cervical cancer.

In cervical cancer (CC), fluorine18-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been proven to be beneficial for patient management. Positron emission tomography/CT is useful in pretreatment evaluation due to the ability to evaluate disease extent and to assess regional lymph nodes as well as distant sites for metastases. Positron emission tomography/CT has an impact on treatment planning as well as it is incorporated in radiation therapy planning, resulting in more appropriate and effective treatment with less cost and radiation dose to normal tissues. Positron emission tomography/CT is used to predict early treatment response and to assess treatment response after completion of concurrent chemoradiation therapy. Positron emission tomography/CT has been used for surveillance after treatment as well as for restaging in suspected recurrent or metastatic disease. Qualitative PET/CT imaging findings as well as quantitative parameters such as maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) are useful to predict prognosis and clinical outcome. Moreover, PET imaging using other radiotracers to detect and quantify hypoxia may help to identify aggressive tumors and predict treatment outcome even though it is not widely clinical used. Positron emission tomography/magnetic resonance imaging (PET/MRI) instruments are now available, which may potentially improve evaluation of primary tumors and metastatic sites given the improved soft tissue contrast resolution of MRI relative to CT. This article reviews the role of 18F-FDG PET/CT, hypoxia agent PET/CT, and 18F-FDG PET/MRI in the management of patients with CC.

Generalized joint hypermobility and voiding dysfunction in children: is there any relationship?

UNLABELLED: Voiding dysfunction is a common entity in pediatric urology. It is believed to have a multifactorial etiology. The aim of this study was to investigate whether there is an increased prevalence of generalized joint hypermobility (GJH) in children with voiding dysfunction compared to normal children. Moreover, the prevalence of voiding complaints in patients with and without GJH was assessed. A total of 226 children--aged 5 to 14 years--including 113 patients diagnosed with voiding dysfunction and 113 sex/age/body mass index-matched normal children were recruited. GJH was evaluated in both groups using the Beighton score (4 or more= hypermobile). In the patient's group, GJH was significantly more frequent than in controls: 51/113 (45 %) versus 19/113 (17 %) (P=0.001). In addition, in both groups, GJH was more prominent in girls than boys (P<0.05). Urinary tract infection was the most frequent features in children with voiding dysfunction (64 %). In the subgroup of positive GJH, urinary tract infection remained the most common manifestation among the girls (P=0.003), while constipation was the most prevalent manifestation among the boys (P=0.001). CONCLUSION: Our findings suggest that children with voiding dysfunction have significantly higher prevalence of GJH compared to normal children. Further studies are needed to determine the cause and effect of these two common presentations and will help to develop a multidisciplinary approach in understanding and management of voiding dysfunction in children.

In Silico Re-Optimization of Atezolizumab Dosing Using Population Pharmacokinetic Simulation and Exposure-Response Simulation.

Atezolizumab, a humanized monoclonal antibody against programmed cell death ligand 1 (PD-L1), was initially approved in 2016, around the same time that the sponsor published the minimum serum concentration to maintain the saturation of receptor occupancy (6 µg/mL). The initially approved dose regimen of 1200 mg every 3 weeks (q3w) was subsequently modified to 840 mg q2w or 1680 mg q4w through pharmacokinetic simulations. Yet, each standard regimen yields steady-state trough concentrations (CMIN,SS ) far exceeding (≈ 40-fold) the stated target concentration. Additionally, the steady-state area under the plasma drug concentration-time curve (AUCSS ) at 1200 mg q3w was significantly (P = .027) correlated with the probability of adverse events of special interest (AESIs) in patients with non-small cell lung cancer (NSCLC) and, coupled with excess exposure, this provides incentive to explore alternative dose regimens to lower the exposure burden while maintaining an effective CMIN,SS . In this study, we first identified 840 mg q6w as an extended-interval regimen that could robustly maintain a serum concentration of 6 µg/mL (≥99% of virtual patients simulated, n = 1000), then applied this regimen to an approach that administers 2 "loading doses" of standard-interval regimens for a future clinical trial aiming to personalize dose regimens. Each standard dose was simulated for 2 loading doses, then 840 mg q6w thereafter; all yielded cycle-7 CMIN,SS values of >6 µg/mL in >99% of virtual patients. Further, the AUCSS from 840 mg q6w resulted in a flattening (P = .63) of the exposure-response relationship with adverse events of special interest (AESIs). We next aim to verify this in a clinical trial seeking to validate extended-interval dosing in a personalized approach using therapeutic drug monitoring.

Immune-Checkpoint Inhibition in the Treatment of Gastro-Esophageal Cancer: A Closer Look at the Emerging Evidence.

To date, several trials have evaluated the safety and efficacy of immune-checkpoint inhibitors (ICI) for the treatment of gastroesophageal cancers (GEC). In the US, ICIs have established indications for second-line treatment of microsatellite unstable tumors, while their use in third-line settings was recently withdrawn. Notably, the use of ICIs for first-line therapy of GEC is rapidly evolving, which currently includes high PD-L1 expressing tumors, irrespective of HER2 status, and in the adjuvant setting after neoadjuvant chemoradiotherapy in select patients. In this article, we review the results of studies that have evaluated the utility of ICI in the third-line, second-line, first-line, and peri-operative treatment settings of GECs. Considerations should be made before making any cross-trial comparisons since these trials vary in chemotherapy backbone, anatomical and histological eligibility, biomarker assessment, PD-L1 diagnostic antibodies, and definition of PD-L1 positivity. Regardless, the totality of the data suggest that first-line ICI use may most benefit GEC patients with high PD-L1 combined positivity score (CPS) ≥5 or ≥10, irrespective of histology or anatomy. Moreover, although PD-L1 by CPS has a good negative predictive value for significant benefit from ICIs, it has a low positive predictive value. Therefore, there is a pressing need to identify better biomarkers to predict benefit from ICIs among these patients.

The Evolving Role of FDG-PET/CT in the Diagnosis, Staging, and Treatment of Breast Cancer.

The applications of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/X-ray computed tomography (PET/CT) in the management of patients with breast cancer have been extensively studied. According to these studies, PET/CT is not routinely performed for the diagnosis of primary breast cancer, although PET/CT in specific subtypes of breast cancer correlates with histopathologic features of the primary tumor. PET/CT can detect metastases to mediastinal, axial, and internal mammary nodes, but it cannot replace the sentinel node biopsy. In detection of distant metastases, this imaging tool may have a better accuracy in detecting lytic bone metastases compared to bone scintigraphy. Thus, PET/CT is recommended when advanced-stage disease is suspected, and conventional modalities are inconclusive. Also, PET/CT has a high sensitivity and specificity to detect loco-regional recurrence and is recommended in asymptomatic patients with rising tumor markers. Numerous studies support the future role of PET/CT in prediction of response to neoadjuvant chemotherapy (NAC). PET/CT has a higher diagnostic value for prognostic risk stratification in comparison with conventional modalities. With the continuing research on the treatment planning and evaluation of patients with breast cancer, the role of PET/CT can be further extended.

The risk of major bleeding in patients with suspected heparin-induced thrombocytopenia.

BACKGROUND: The presence of a hypercoagulable disorder such as heparin-induced thrombocytopenia (HIT) may protect against anticoagulant-associated bleeding. OBJECTIVES: To determine the incidence of major bleeding in patients with suspected HIT. METHODS: We performed a retrospective analysis of 310 patients suspected of having HIT from the Hospital of the University of Pennsylvania and an affiliated community hospital. We compared the cumulative incidence of major bleeding following suspicion for HIT by ultimate HIT status (HIT+ or HIT-) and exposure to an alternative anticoagulant (Tx+ or Tx-). Secondary outcomes included the incidence of new/progressive thrombosis and 30-day mortality. RESULTS: The incidence of major bleeding was high in the HIT+Tx+, HIT- Tx+, and HIT-Tx- groups (35.7%, 44.0%, and 37.3%, respectively). The time to first major bleeding event did not differ between groups (P = .24). Factors associated with increased risk of major bleeding included intensive care unit admission (HR 2.24, 95% CI 1.44-3.47), platelet count < 25 × 109 /L (HR 2.13, 1.10-4.12), and renal dysfunction (HR 1.56, 1.06-2.27); 35.7% of HIT+Tx+, 13.8% HIT-Tx+, and 9.3% of HIT-Tx- patients experienced new or progressive thrombosis. Mortality was similar among the three groups (26.2% HIT+Tx+, 34.5% HIT-Tx+, and 26.7% of HIT-Tx- [P = .34]). CONCLUSIONS: Among patients with suspected HIT, major bleeding was common regardless of HIT status. Contrary to our hypothesis, HIT+ patients were not protected from major bleeding. A better understanding of bleeding risk is needed to inform management decisions in patients with suspected HIT.

Enrollment Barriers for Molecular Targeted Trials.

This quality improvement study examines the difficulties of patient accrual among patients with cancer and SETD2 variants.

Prospective comparison of the HEP score and 4Ts score for the diagnosis of heparin-induced thrombocytopenia.

The HIT Expert Probability (HEP) score compared favorably with the 4Ts score in a retrospective study. We assessed the diagnostic accuracy of the HEP score compared with the 4Ts score in a prospective cohort of 310 patients with suspected heparin-induced thrombocytopenia (HIT). A member of the clinical team calculated the HEP score and 4Ts score. An independent panel adjudicated HIT status based on a clinical summary as well as the results of HIT laboratory testing. The prevalence of HIT in the study population was 14.7%. At a cutoff of ≥3, the HEP score was 95.3% sensitive (95% confidence interval [CI], 84.2-99.4) and 35.7% specific (95% CI, 29.8-42.0) for HIT. A 4Ts score of ≥4 had a sensitivity of 97.7% (95% CI, 86.2-99.8) and specificity of 32.9% (95% CI, 27.2-39.1). The areas under the receiver operating characteristic (ROC) curves (AUCs) for the HEP score and 4Ts score were similar (0.81 [95% CI, 0.74-0.87] vs 0.76 [95% CI, 0.69-0.83]; P = .12). The HEP score exhibited a significantly higher AUC than the 4Ts score in patients in the intensive care unit (ICU) (0.86 vs 0.79; P = .03). Among trainee scorers, the HEP score performed significantly better than the 4Ts score (AUC, 0.80 vs 0.73; P = .03). Our data suggest that either the 4Ts score or the HEP score may be used in clinical practice. The HEP score may be preferable in ICU patients and among less experienced clinicians.

Impulsivity, Sensation Seeking, and Risk-Taking Behaviors among HIV-Positive and HIV-Negative Heroin Dependent Persons.

Objective. The aim of this study was to compare impulsivity and risky decision making among HIV-positive and negative heroin dependent persons. Methods. We compared different dimensions of impulsivity and risky decision making in two groups of 60 HIV-positive and 60 HIV-negative male heroin dependent persons. Each group was comprised of equal numbers of current (treatment seeker) and former (abstinent) heroin addicts. Data collection tools included Balloon Analogue Risk Task (BART), Iowa Gambling Task (IGT), Barratt Impulsiveness Scale (BIS), and Zuckerman Sensation Seeking Scale (SSS). Results. In SSS, comprised of four subscales including thrill and adventure seeking (TAS), experience seeking (ES), disinhibition (DIS), and boredom susceptibility (BS), there was a borderline difference in DIS (P = 0.08) as HIV-positive group scored higher than HIV-negative group. Also, ES and total score were significantly higher among HIV-positive patients. In BART, HIV-positive subjects scored higher in risk taking than HIV-negative subjects as reflected in higher Average Number of puffs in Successful Balloons (ANSB). In BIS, HIV-positive group scored significantly higher in cognitive impulsivity (CI) (P = 0.03) and nonplanning impulsivity (NPI) (P = 0.05) in comparison to HIV-negative group. Also, current heroin addicts scored significantly higher in NPI compared to former addict HIV-negative participants (P = 0.015). IGT did not show any significant difference between groups. Conclusion. Higher levels of impulsivity and risk taking behaviors among HIV-positive heroin addicts will increase serious concerns regarding HIV transmission from this group to other opiate dependents and healthy people.

Elevated serum levels of pregnancy-associated plasma protein-A in type 2 diabetics compared to healthy controls: associations with subclinical atherosclerosis parameters.

Type 2 diabetes mellitus is associated with increased inflammation and accelerated atherosclerosis. The association of the pro-inflammatory and potentially pro-atherosclerotic molecule, pregnancy associated plasma protein-A (PAPP-A) with diabetes and vascular diseases remains to be further established. A total of 107 patients with type 2 diabetes and 101 healthy controls participated in this study. Serum levels of PAPP-A was measured by Enzyme-linked Immunosorbent Assay (ELISA). We also evaluated the lipid profile, aortic augmentation index, coronary calcium score, ankle brachial index, flow mediated dilation, and carotid intima media thickness. Serum level of PAPP-A was significantly higher in patients with diabetes compared to controls (P<0.001). In the multivariable regression analysis, PAPP-A was positively correlated with diabetes (P<0.001), aortic augmentation index (P=0.021) and was negatively associated with coronary calcification (P=0.050). In conclusion, serum levels of PAPP-A were significantly higher in diabetics compared to healthy controls and correlated with aortic augmentation index and coronary calcification. Our study results suggest that PAPP-A can be a marker of subclinical atherosclerosis in patients with diabetes.

Penile Skin Involvement as the First Presentation of Henoch-Schonlein Purpura Report of Nine Cases and Review of Literature.

INTRODUCTION: Involvement of penis is a rare presentation in henoch-schonlein purpura (HSP). The presentations are mainly due to the deposition of immunoglobulin A (IgA) into the vessel walls. In this report, we present the clinical history of nine HSP cases that presented with penile skin involvement. CASE PRESENTATION: All patients were referred in the acute phase of HSP. Penile skin involvement was evident as erythema, edema, ecchymosis, or induration of prepuce and/or penile shaft, that appeared simultaneously with skin rash in seven patients. Gastrointestinal involvement was positive in six patients. Patients were treated with steroids and follow up visits were normal except for one patient that developed crescentic glomerulonephritis. CONCLUSIONS: We present nine cases of HSP with penile involvement in order to indicate another rare aspect of HSP and its possible complications as well as its appropriate treatment.