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

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.

Thyroid dysfunction is a common endocrine side effect of immune checkpoint inhibitors (ICI). We designed a retrospective study, including patients who received ICI for any cancer at our institution. Thyroid-stimulating hormone (TSH), free T4 levels, and time to development of thyroid dysfunction were measured, and medication used to treat thyroid dysfunction were identified. We reviewed the charts of 104 patients with complete records obtained from our tumor registry. A total of 91 patients were included in the analysis, after excluding 13 patients with a pre-existing thyroid disorder. Twenty-eight (30.77%) patients developed thyroid dysfunction after starting ICI. Race (p-0.048), age (p-0.014), history of radiation therapy (RT) to the neck (p-0.004), history of RT to the chest (p-0.012), and history of venous thrombosis (p-0.004) were significantly associated with thyroid dysfunction on univariate analysis. For multivariate analysis, the history of RT to the neck, adjusted for age, race, and sex, was significantly associated with thyroid dysfunction (adjusted OR-9.64, 95%CI: 1.88, 49.36, p-0.007). In patients receiving ICI for any type of cancer, the previous history of RT to the neck was significantly associated with the development of thyroid dysfunction after starting ICI.

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 β = 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.

Simple Summary Gastroesophageal cancers (GEC) constitute a common group of tumors that vary highly in incidence and treatment response. Although chemotherapy is the mainstay of treatment, immunotherapy with immune-checkpoint inhibitors (ICI) is a novel treatment modality for this type of cancer. To date, several studies have evaluated the safety and efficacy of ICIs for the treatment of GEC. The role of ICIs in the treatment of GEC is rapidly evolving. 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 includes high PD-L1 expressing tumors, irrespective of HER2 status, and in the adjuvant setting after neoadjuvant chemoradiotherapy in select patients. In this review, we outline the results of these studies for the third-line, second-line, first-line, and peri-operative treatment of GEC. Abstract 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.

407 Background: It has been hypothesized that the rarity of molecular inclusion criteria hampers trial accrual. In this study, we attempted to address this challenge in the context of a SETD2-mutation targeted trial. Methods: Patients who received molecular sequencing services from Tempus were analyzed for the presence of SETD2 molecular variants that matched trial enrollment criteria, and resided within 50 miles from the treatment center or were receiving treatment at clinical sites with strong referral histories. A written notification was issued to the ordering physician whenever a likely match was identified, and additional phone and email outreach follow up, including reasons for not pursuing the clinical trial, was conducted. Results: Over one year, 38 eligible patients were identified, none of which were enrolled. The most common reason for not being enrolled was cohort closure following initial identification and outreach. More specifically, cohort closure occurred < 2 months, 2-4 months, 4-6 months and > 6 months following identification of the mutation in 5, 8, 2 and 7 patients, respectively. Physicians for additional potential patients cited trial consideration as a future option, presence of prohibitive comorbidities, lack of interest, and patient death in 6, 3, 2 and 1 patients, respectively. Physicians for 4 patients did not respond to multiple follow up attempts. In regards to individual follow up, physicians received 0-1, 2-3, and 4 or more follow up outreach notifications regarding trial availability for 14, 19, and 5 patients respectively. Conclusions: Despite identification of a large number of potential trial candidates for a molecular targeted therapeutic trial through use of matching algorithms and extensive treating physician follow up, no patients were enrolled. This raises the hypothesis that the biggest barrier to enrollment, as in other settings, is treating physician motivation and that AI algorithms for identifying potential subjects are insufficient. Larger target populations than anticipated, better coordination between outreach efforts and enrollment status, and directed patient outreach may be necessary.

e15609 Background: HG-NEC of the GI tract are rare and aggressive neoplasms with poor prognosis. Approximately 37.5% of extra-pulmonary NEC are of the GI origin and are most commonly located in esophagus, stomach, pancreas and colon (1,2). Median survival of 7.5 months, with range of 5.7 months to 25.1 months has been reported (2). However, data regarding response to immunotherapy, as well as response to molecularly directed therapies are sparse. In this study, we conducted a retrospective review of GI tract HG-NEC with objective to assess role of modern diagnostics and therapies in clinical outcomes. Methods: We identified 14 patients with GI tract HG-NEC who received care at University of Chicago Medical Center (UCMC). Electronic medical records were reviewed for disease stage, treatments and clinical course. We reviewed available next generation sequencing (NGS) and circulating tumor DNA (ct-DNA) test results. In this cohort, UCMC’s NGS panel: Oncoplus was available and Guardant 360 results were reviewed for liquid biopsy. Results: In our initial review, site of origin included right side of colon (46%), left sided colon (46%), and anus/anorectal (15%). Median overall survival (mOS) ranged from 1.3 months to 81.3 months, and notably the median response to chemo-immunotherapy (IO) was 7.9 months (table 1). Notably one patient received maintenance therapy with immunotherapy alone with progression of disease (POD) in 3 weeks. Six patients had NGS results of which three (50%) had therapeutic targetable alterations (Table). Two patients had liquid biopsy done, of which one had targetable alterations and the other had no tumor related alterations detected. Of the two patients with targetable lesions, one patient has received targeted therapy with POD in 1.2 months and median OS 8.8 months; the other is in the process of initiating targeted therapy. Conclusions: To our knowledge, this is the first report to show a response to combination chemo-immunotherapy and targeted therapies in HG-NEC of GI tract. We are collaborating with other institutions to collate outcomes to similar therapy approaches in this patient cohort. With our study, we hope to inform future therapies and innovation in this important disease.

316 Background: 5FU, Ox, Iri, and Tax are each active in upper GI cancers. Triplet cytotoxic therapies (txs) improved survival compared to doublets/singlets. However, combination of all 4 agents (FOLFOXIRITAX) has not been studied. UGT1A1 polymorphisms reduce UGT enzymatic activity predisposing to Iri toxicity. We sought to determine the maximum tolerated dose (MTD) in the 1st month of tx among each of the low (L), intermediate (I) and high (H) risk UGT1A1 genotype (UGT) groups. Methods: Previously untx’d advanced upper GI cancer patients (pts) with ECOG PS 0/1 received gFOLFOXIRITAX (+ trastuzumab if HER2+) with pegfilgrastim. 5FU 2400mg/m2 over 46 hrs, LV 400mg/m2, Ox 85mg/m2, and Tax 25mg/m2 were given IV Q14 days. UGT-L, I, and H risk groups received starting Iri dose levels (DL1) of 120, 105 and 45mg/m2, respectively; Iri doses were escalated in each UGT group by 15mg/m2 increments and Tax to DL2 of 37.5mg/m2 using a I3+3 novel design (Liu & Ji. J Biopharm Stat 2020). Other endpoints included overall safety (thru up to 8 cycles before maintenance 5FU +/- Iri/tras), ORR (RECIST1.1), & ctDNA response (> 50% decrease in highest MAF) by G360 (Guardant Health). Results: From 6/30/2020-8/6/2021 20 pts (8F, 12M) enrolled: median age 50 (range 21-76); 8 ECOG PS 1, UGT-L:I:H with 3:14:3 pts; 10 esophageal, 6 gastric, 2 pancreatic, 1 unknown GI primary and 1 bile duct cancer; 2 pts HER2+; 18 metastatic, 2 locally advanced unresectable. The median (range) of albumin and neutrophil-to-lymphocyte ratio (NLR) were 3.9 mg/dL (3.3-4.6) and 4.28 (1.89-27.6), respectively; 80% (16/20) of pts had a NLR > 2.88, a poor prognostic marker. Dose limiting toxicities (DLTs) were seen in 4 pts: one G3 diarrhea (UGT-H, DL1/DL1 Iri/Tax), two G3 sepsis not neutropenic (one UGT-I, DL2/DL2 Iri/Tax; and one UGT-I, DL3/DL1 Iri/Tax) and one G3 fatigue (UGT-I DL2/DL2 Iri/Tax). MTD has not been reached in any UGT TAX DL1 cohorts to date; currently enrolling UGT-H Iri/Tax DL1/DL1, UGT-I DL4/DL1, & UGT-L DL3/DL1. Any Gr tx related toxicities in ³ 10% pts thru up to 8 cycles: nausea (70%), fatigue (70%, 5% G3), diarrhea (65%, 5% G3), anorexia (50%), peripheral neuropathy (30%, 5% G3), anemia (30%), thrombocytopenia (25%), elevated LFTs (25%), hyponatremia (25%), vomiting (20%), mucositis (20%, 5% G3), hyperglycemia (20%), edema (15%), alopecia (15%), hypocalcemia (15%) and dysgeusia (10%). Of evaluable pts across all cohorts, PR/CR was seen in 13/16 (81%) patients, with 2 (12.5%) SD and 1 (6.25%) PD for a disease control rate of 94%. Of evaluable pts, best ctDNA response was seen in 12/13 (92%). Conclusions: gFOLFOXIRITAX demonstrated tolerability at initial dose levels of Iri/Tax, with dose escalation continuing. Efficacy is promising and could be an aggressive approach in upper GI cancers having high relapse risk in curative-intent settings. Clinical trial information: NCT04361708.

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

We aimed to assess the correlation between age and cardiovascular risk factors with NaF-PET/CT imaging in the thoracic aorta (TA).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.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, p0.001). ACS of the entire TA was a stronger predictor of FRS compared with average SUVmax and average SUVmean (adjusted RActive 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.• 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.

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.

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.

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

Background: Non-Hispanic Black (NHB) and Hispanic patients with Acute Myeloid Leukemia (AML) have higher mortality rates than non-Hispanic white (NHW) patients despite lower incidence, more favorable genetics, and a younger age at presentation (Darbinyan, Blood Adv. 2017). We performed a multilevel analysis of disparities in AML patients to investigate the contribution of structural violence, specifically neighborhood SES, on racial/ethnic differences in leukemia-specific survival. Methods: Adult AML (non-APL) patients diagnosed between 2012 and 2018 at six academic cancer centers in the Chicago area were included. Census tract data was collected using the FFIEC Geocoding/Mapping System and computed tract disadvantage and tract affluence scores were categorized into distribution tertiles (low, moderate, high). Time to relapse and death from leukemia were examined, adjusting for age, gender and race/ethnicity (baseline models), and for potential mediators of racial disparities including distal (Charlson Comorbidity Index (CCI), obesity, concentrated disadvantage and affluence, health insurance status), and proximal mediators (somatic mutations, and European Leukemia Network (ELN) prognostic score categories). Results Patient characteristics are shown in Table 1 (n = 822). Significant heterogeneity in age and comorbidities at diagnosis was observed, with Hispanic patients being the youngest and with the lowest CCI. Morbid obesity was more prevalent in NHB and Hispanic (23% and 20%, respectively) compared with NHW (11%) patients. Payer source also differed significantly; private insurance was twice as frequent among NHW than NHB (51% vs. 25%) patients, while the largest uninsured population was Hispanic. ELN adverse risk disease was most prevalent in NHW subjects, NPM1 mutations were least prevalent in Hispanic patients, and p53 mutations more prevalent in NHB (26%) compared to NHW (12%) and Hispanics (9%) although due to low numbers this did not reach significance (p=0.10). NHB and Hispanic patients tended to reside in more disadvantaged and less affluent areas. Treatment data was available for 764 patients (Table 2); 75% received intensive induction therapy and choice of first-line treatment did not differ by race or tract disadvantage. Allogeneic transplant rates however differed by race, age, insurance status, tract disadvantage, and ELN score. Treatment complications of induction chemotherapy, as reflected by ICU admissions during induction, were significantly lower in NHW (25%) compared to NHB (39%) and Hispanic (42%) patients. ICU admission rates were significantly higher in patients with morbid obesity and low tract affluence. Minority (vs. NHW) ethnicity was associated with a 42% increased hazard of death from leukemia (HR=1.42, 95% CI: 1.09, 1.85), and a 36% increased hazard of death from all causes (HR=1.36, 95% CI: 1.07, 1.72), each after controlling for age, gender and study site. Adjustment for continuous tract disadvantage and affluence and their interaction lowered both the hazard of leukemia and all cause death to 1.18 (95% CI: 0.88, 1.60) and 1.14 (95% CI: 0.88, 1.49), respectively. In formal mediation analysis, neighborhood SES accounted for 37% (p=0.09) and 50% (p=0.02) of the racial disparity in death from leukemia and all causes, respectively. Discussion: This study is the first to integrate data at the individual patient level with neighborhood characteristics, using census tract level variables to examine their contribution to AML patient outcomes. To date, formal mediation methods had not been employed to disentangle race/ethnic disparities in adult AML survival. Notably, our mediation analysis shows that census tract level SES explains a substantial proportion of the disparity in hazard of leukemia death. In addition, the observed disparities in treatment complications of induction chemotherapy, as reflected by ICU admissions, and the continued disparity in allogeneic transplant utilization all warrant further study. These results draw attention to the need for deeper investigation into the social and economic barriers to successful treatment outcomes for leukemia patients and represent an important first step toward designing strategies to mitigate these persistent health inequities. Disclosures Altman: Janssen: Consultancy; Syros: Consultancy; Genentech: Research Funding; Novartis: Consultancy; Amphivena: Research Funding; Amgen: Research Funding; Aprea: Research Funding; ImmunoGen: Research Funding; Celgene: Research Funding; Boehringer Ingelheim: Research Funding; Fujifilm: Research Funding; Kartos: Research Funding; AbbVie: Other: advisory board, Research Funding; Kura Oncology: Other: Scientific Advisory Board - no payment accepted, Research Funding; BioSight: Other: No payment but was reimbursed for travel , Research Funding; Daiichi Sankyo: Other: Advisory Board - no payment but was reimbursed for travel; Agios: Other: advisory board, Research Funding; Glycomimetics: Other: Data safety and monitoring committee; Astellas: Other: Advisory Board, Speaker (no payment), Steering Committee (no payment), Research Funding; Theradex: Other: Advisory Board; Immune Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy; France Foundation: Consultancy; PeerView: Consultancy; PrIME Oncology: Consultancy; ASH: Consultancy; Cancer Expert Now: Consultancy. Stock:Research to Practice: Honoraria; UpToDate: Honoraria; Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Society of Hematology: Honoraria; Leukemia and Lymphoma Society: Research Funding; Novartis: Research Funding; Abbvie: Honoraria, Research Funding; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Quigley:Alnylam: Speakers Bureau; Agios: Speakers Bureau; Amgen: Other: Advisory board. Khan:Celgene: Consultancy; Incyte: Honoraria; Takeda: Research Funding; Amgen: Consultancy.

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.

SummaryWhat is known and objective N-acetylcysteine (NAC) has been proposed as a potential therapy for obsessive–compulsive disorder (OCD) as it may regulate the exchange of glutamate and prevent its pre-oxidant effects. The aim of the present double-blind, placebo-controlled trial was to assess the efficacy and tolerability of NAC augmentation in moderate-to-severe (OCD) treatment. Methods In this randomized, double-blind, two-centre, placebo-controlled, 10-week trial, patients with moderate-to-severe OCD were enrolled. Patients were randomized into two parallel groups to receive fluvoxamine (200 mg daily) plus placebo or fluvoxamine (200 mg daily) plus NAC (2000 mg daily). A total of 44 patients (22 in each group) were visited to evaluate response to therapy 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 upon each visit. Results and discussion Repeated-measures ANOVA showed a significant effect for time × treatment interaction (Greenhouse–Geisser corrected: F = 5·14, d.f. = 1·64, P = 0·012) in the Y-BOCS total score and a significant effect for time × treatment interaction (Greenhouse–Geisser corrected: F = 5·44, d.f. = 1·54, P = 0·011) in the Y-BOCS obsession subscale between the two groups. What is new and conclusion Our results showed that NAC might be effective as an augmentative agent in the treatment of moderate-to-severe OCD. Trial registration Iranian Registry of Clinical Trials (www.irct.ir): IRCT201405271556N60

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.

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 (This study was part of the cardiovascular molecular calcification assessed byThe 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 (P0.001). 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 (P0.001). 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).In conclusion, these findings confirm a significant age dependent reduction of supratentorial

Background: Non-Hispanic Black (NHB) and Hispanic patients with Acute Myeloid Leukemia (AML) have higher mortality rates than non-Hispanic white (NHW) patients despite a lower incidence of disease, more favorable genetics and younger age at presentation (Patel. AJCO 2015). It is unknown whether these disparities are linked to disease biology or treatment approach. Prior large database analyses have suggested that differences in AML outcomes may be impacted by socioeconomic factors such as insurance status and household income but lack data regarding treatment details including complications and molecular disease features (Bhatt. Blood Advances 2018). We postulate that increased mortality rates for NHB and Hispanic patients with AML are driven by disparities in treatment patterns when adjusted for baseline disease risk. Methods: We have analyzed data collected on consecutive adult patients diagnosed with AML between 2012 and 2018 from 5 academic cancer centers in Chicago surveying different population subsets using an IRB approved protocol. Figure 1 shows insurance status of the patient cohort by zip code. Cox proportional hazards models will be used to estimate multivariable-adjusted hazard ratios for relapse and mortality. Baseline models will be adjusted for age, gender and race/ethnicity to estimate the hazard ratios for the NHB-NHW and Hispanic-NHW disparities in time to relapse and treatment-related or disease-related mortality. Results: At the time of abstract submission 263 subjects were included in the analysis. The study is actively accruing at all 5 institutions with a database goal of 700 patients. There are significant differences in baseline characteristics by race/ethnicity (Table 1). NHB patients are younger, less likely to be married, and less likely to be privately insured than NHW (20% vs >51%). Hispanic patients are younger and more likely to be uninsured than NHW patients (30% vs 6%), likely reflective of County Hospital patients. In this preliminary dataset, clinical trial enrollment rates were similar by race/ethnicity. The distribution of ELN risk groups (Dohner. Blood 2017) and therapy-related AML (t-AML) cases were also similar by race/ethnicity. Eighty percent of patients received intensive induction chemotherapy (Fig 2). Receipt of intensive therapy did not differ by race but was more prevalent in younger patients and uninsured patients (Table 2), likely related to concerns about outpatient medication coverage. Elderly, adverse ELN risk and t-AML patients were less likely to receive intensive chemotherapy, likely due to poorer performance status in the elderly and potential chemo-resistance in p53mut AML. Treatment complications during induction chemotherapy, as captured by ICU admissions, were significantly lower in NHW patients, and significantly increased in morbidly obese patients. Treatment failure, by IWG criteria, did not differ by race but rather was determined by disease specific factors including ELN group, and t-AML. Relapse risk was higher in FLT3-ITD mutant cases. Allogeneic transplant rates did not differ significantly by race but were higher in adverse ELN groups and in privately insured patients. Two-year survival was affected by individual and disease specific factors including age, Medicare enrollment, t-AML and ELN risk group. Discussion: Our current dataset (n = 263) highlights disparities in treatment approaches in patients with AML. These include i) the preferential utilization of intensive induction chemotherapy in younger patients and those lacking high risk molecular features, and ii), the influence of payer status and molecular risk on utilization of allogeneic stem cell transplant in first remission. Treatment outcomes in AML were also impacted by patient age, morbid obesity, marital status, and payer source in addition to known prognostic disease-specific factors (ELN risk group and t-AML). This large multi-institutional study has advantages over population-based registries (SEER, NCDB) through incorporation of molecular characteristics, treatment responses and tolerability data not available in public datasets, which can provide insight into biologic intermediates contributing to disparities. Ongoing analyses will examine how variables such as the comorbidity index and measures of socioeconomic status interact with molecular risk factors to determine outcomes in this diverse patient population. Disclosures Stock: Research to Practice: Honoraria; Kite, a Gilead Company: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Daiichi: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees; UpToDate: Honoraria. Galvin:Incyte: Consultancy. Altman:prIME Oncology: Speakers Bureau; PeerView: Speakers Bureau; Theradex: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Glycomimetics: Consultancy, Honoraria, Other: Data Safety and Monitoring Committee; Daiichi Sankyo: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Cancer Expert Now: Consultancy; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; France Foundation: Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Biosight: Other: US Lead. Quigley:Alexion: Membership on an entity's Board of Directors or advisory committees; Alnylam: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Dova Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; TEVA: Research Funding. Khan:Amgen: Consultancy; Celgene: Consultancy; Incyte: Honoraria; Pfizer: Consultancy; Takeda: Research Funding.

Adequate adherence to anti-retroviral therapy is required to achieve viral suppression and desirable treatment outcomes among HIV patients. The aim of this study was to examine the associations between adherence and severity of substance use as well as adherence and severity of depressive symptoms among Iranian HIV patients. In a prospective study, HIV patients with current substance use were assessed for adherence level via self report and pill count methods, severity of depressive symptoms (Beck Depression Inventory- II) and substance use (Addiction Severity Index) during a three months follow up after initiating antiretroviral therapy. The adherence level, severity of depressive symptoms and substance use were assessed one month, two months and three months after initiation of anti-retroviral therapy. Addiction Severity Index (ASI) composite scores were calculated for each domain and the associations between ASI domains and adherence as well as severity of depressive symptoms and adherence were assessed. Twenty six HIV patients with current substance use disorder completed the study. At the end of the first month, adherence to therapy via pill count and self-report were 80%±31.9% and 85.12%±32%, respectively. At the end of the second month, adherence to therapy via pill count and self report were 87%±32% and 93.94%±23% respectively. At the end of the third month, the measured adherence via pill count and self report were 85%±33.7% and 90.1%±25.7% respectively. Adherence was higher among married patients and those who used reminder systems. Composite scores of the medical status and psychiatric status were related to higher adherence after first month. Substance use was inversely associated with adherence at the second follow up (r=-0.4, p=0.04). Also, severity of depressive symptoms was not related to adherence level. The repeated measurement analysis showed a significant decrease in psychiatric status domain of the ASI composite score after three months of initiating therapy (p=0.02). Preventive measures should aim treatment of substance use among HIV patients in order to increase adherence level. Also, conducting psychological evaluations is necessary considering the high prevalence of depression among Iranian HIV patients.

Anti-retroviral drug resistance evolves as an inevitable consequence of expanded combination Anti-retroviral Therapy (cART). According to each drug class, resistance mutations may occur due to the infidel nature of HIV reverse transcriptase (RT) and inadequate drug pressures. Correspondingly, resistance to Nucleoside Reverse Transcriptase Inhibitors (NRTIs) occurs due to incorporation impairment of the agent or its removal from the elongating viral DNA chain. With regard to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), resistance mutations may alter residues of the RT hydrophobic pocket and demonstrate high level of cross resistance. However, resistance to Protease Inhibitors requires complex accumulation of primary and secondary mutations that substitute amino acids in proximity to the viral protease active site. Resistance to novel entry inhibitors may also evolve as a result of mutations that affect the interactions between viral glycoprotein and CD4 or the chemokine receptors. According to the current studies, future drug initiative programs should consider agents that possess higher genetic barrier toward resistance for ascertaining adequate drug efficacy among patients who have failed first-line regimens.

e14134 Background: Immune-related endocrine dysfunction is unique to immunotherapy (IT). We aimed to explore the clinical parameters associated with development of thyroid disorder (TD) in patients receiving IT and their outcome. Methods: We designed a retrospective study of patients treated with anti-CTLA4 and/or anti-PD1/PDL1 IT at Cook County Hospital, Chicago between January 2015 to January 2018. Patients with incomplete charts and those who received less than two cycles of IT were excluded. Demographics, clinical and pathologic data were recorded at the time of diagnosis and prior to start of IT. Pearson Chi-square, independent sample t-test and logistic regression were used for data analysis. Results: We included 104 patients in the study, out of whom 66 were male and 38 were female. Most common diagnosis was non-small cell lung cancer (42.4%) followed by squamous cell cancer of head and neck (21.2%), renal cell cancer (12.5%), small cell lung cancer (12.5%) and melanoma (8.7%). Majority of patients (91.4%) had metastasized and were treated with either Nivolumab (71.1%) or Pembrolizumab (21.2%) in the 2nd (50%) or 3rd line (29.8%) setting. Twenty-eight patients developed TD while on IT, out of whom, 13 developed hypothyroidism, 12 developed hyperthyroidism followed by hypothyroidism and 3 developed hyperthyroidism. TD developed between 1st to 6th cycle of IT in 96.5% patients. Older age (p-0.009), history of radiation (RT) to neck (p-0.007), history of RT to chest (p-0.015), history of venous thrombosis (p-0.007) and higher thyroid stimulating hormone (TSH) level (17.76±35.67) prior to starting IT (p-0.029) were significantly associated with TD. Multivariate logistic regression showed that history of RT to neck was a significant predictor of developing TD after adjustment for age, race and sex (adjusted OR 9.64, 95% CI 1.88-49.36, p-0.007). No patient reported thyroid related symptom and IT was continued uninterrupted in all patients. Levothyroxine was the drug of choice for treating hypothyroidism. No patient received steroids or antithyroid medications. Conclusions: History of radiation therapy to neck is significantly associated with development of thyroid dysfunction in patients receiving immunotherapy. Thyroid replacement therapy is sufficient to bring down the levels of TSH and immunotherapy need not be interrupted.

Background: Stigma and discrimination are among the main barriers for health workers to provide appropriate and necessary services for People Living with HIV/AIDS (PLWHA). Objectives: We conducted this study in Iran, to evaluate Stigma Index and the correlates. Materials and Methods: In this cross-sectional study, 289 HIV positive patients were recruited from six cities in Iran (including Tehran, Shiraz, Mashhad, Tabriz, Ahvaz and Kermanshah) to fill out the Farsi version of Stigma Index questionnaires through interviews that were arranged by two HIV infected persons for each city who were experienced data collectors. Results: Two hundred eighty nine HIV infected patients were interviewed by the trainers, out of which 90.3% and 9.7% were male and female, respectively. Most participants (47.8%) were in 30 - 39 years old age group. Sixty two point two percent of participants experienced external stigma and 98.62% subjects reported internal stigma. Significant associations between the cities and some items including external stigma, level of awareness regarding policies, rights and laws, feeling pressure to disclose HIV status and access to anti-retroviral therapy (ART) were observed. Conclusions: HIV patients have limited access to occupation, educational and health services. Policies should be made to target the high level of both perceived and external stigma among Iranian PLWHA.

Introduction: Rivaroxaban is a target specific oral anticoagulant approved for treatment of deep venous thromboembolism (DVT), pulmonary embolism (PE) and risk reduction in patients with DVT/PE requiring continued anticoagulation. The XALIA study showed a reduced bleeding risk compared to standard anticoagulation therapy; however, there is paucity of data regarding correlates of bleeding risk amongst patients receiving rivaroxaban in the community setting. We aimed to investigate the clinical factors associated with bleeding events (BE) in patients receiving rivaroxaban for treatment of DVT/PE. Methods: A retrospective study was conducted at John H. Stroger, Jr. Hospital of Cook County. We screened the charts of 837 patients who received rivaroxaban from January 1, 2015 to April 01, 2018. Patients with DVT/PE were included in the study (n=271). Patients with atrial fibrillation and those receiving rivaroxaban for prophylaxis were excluded. Any reported BE was recorded as either major or minor bleeding event. Major BE was defined as events requiring hospitalization, blood transfusions or significant drop in hemoglobin (>2gm/dL). Rest of the BE were classified as minor BE. Socio-demographic and clinical factors were collected. Chi-square test and fisher exact test were used as the tests of trend. Multivariate logistic regression models were used to quantify the independent predictors. Odds ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CI) were obtained. Results: The study included 271 patients, of which 68.3% were African-American, 14.4% were Caucasian, and 12.9% were Hispanic. Median age was 53 years and 60.9% patients were men. Bleeding events were reported in 11.4% (n=31) patients with 6.3% major bleeding events and 5.2% minor bleeding events. Only concurrent use of aspirin (23.8% vs. 9.2%; OR 3.10, 95% CI 1.34-7.17, P = 0.008) was significantly associated with bleeding events. None of the clinical parameters, like abnormal liver function tests (11.4%), cirrhosis (3.3%), chronic kidney disease stage 3 or worse (7.6%), prior use of warfarin (29.9%) or low molecular weight heparin (18.1%) were associated with bleeding events. In multivariate model adjusted for age, gender and race, concurrent use of aspirin (aOR 3.06, 95% CI 1.23-7.62, P = 0.017) remained independent predictor of bleeding events. Conclusion: In the community practice, aspirin (81mg or 325mg) is prescribed for cardio-protection. A recently concluded trial showed a better cardioprotective effect of combining rivaroxaban and aspirin, without increase in BE in patients with stable cardiovascular disease. However, such data is not evident in patients receiving rivaroxaban for DVT/PE. Our study shows an increased rate of bleeding events in such patients with concurrent use of aspirin. Our study population comprises of two-third African-American patients who are under-represented in the clinical trials. Based on our results we would suggest further investigation in safety of prescribing aspirin with rivaroxaban in patients with DVT/PE in prospective trials. Disclosures No relevant conflicts of interest to declare.

After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world; however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint.

Background: Due to the increase of HIV patients’ survival, rheumatologic symptoms associated with HIV such as septic arthritis, psoriatic arthritis and other manifestations have increased. Also, diseases such as systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA) can be intensified during AIDS. Objectives: The aim of this cross-sectional study was to evaluate the prevalence and nature of rheumatologic manifestations in HIV positive patients, Tehran, Iran. Materials and Methods: This cross-sectional investigation was done on 200 HIV infected patients from 2009 to 2010. Demographic characteristics (age and sex), the route of HIV transmission and the duration of infection, existence of any concurrent infection such as hepatitis B (HBV) and hepatitis C (HCV) infections, last CD4 count, regimen and duration of the anti-retroviral therapy, presence of any musculoskeletal manifestation and joint disease and their quantity and quality were obtained. Patients were also examined by a clinician and information was recorded via checklists. Data were analyzed using SPSS software and reported as means and percentages. Results: Two hundred HIV patients including 153 male and 47 female participated in the study. Sixty three patients (31.5%) had musculoskeletal manifestations. The most prevalent complaints were arthralgia in 25 patients (39.7%), myalgia in seven patients (11.1%) and unspecified spondyloarthritis in four patients (6.3%). Also, a borderline association was observed between HBV-HIV co-infection and presence of musculoskeletal findings (P = 0.047). Conclusions: Considering the high prevalence of rheumatologic manifestations in patients with HIV/AIDS and its probable relation to the quality of life of patients, there is a pressing need for evaluating patients in this regard, especially among patients who are receiving highly active anti-retroviral therapy (HAART) and experience better clinical responses.

Although Highly Active Anti-Retroviral Therapy (HAART) significantly reduced HIV/AIDS mortality, appropriate adherence level is recommended for viral suppression and therapeutic response in People Living with HIV/AIDS (PLWHA). In the most studies, adherence is defined as taking ≥95% of prescribed medications. Poor or non-adherence may lead to treatment failure and drug resistance. There is no golden standard for evaluation of adherence to medication and many measurement methods are used to assess adherence rate. Moreover, several determinants have been contemplated for adherence in different studies; however, the exact roles of some determinants are not well established. The goals of this review are to describe the adherence rates, to discuss the advantages and disadvantages of common adherence measurement methods, to examine significant correlations related to adherence and to recommend strategies for improving adherence in clinical care.

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.

In cervical cancer (CC), fluorine18-fluorodeoxyglucose (

Introduction: Pulmonary hypertension (PHT) is a common complication in β-thalassemia. We aimed to determine the prevalence of PHT and its main indicators in patients with β thalassemia Major (TM) and β-thalassemia Intermedia (TI), considering left ventricular function.Methods: Pulmonary hypertension (PHT) is a common complication in β-thalassemia. We aimed to determine the prevalence of PHT and its main indicators in patients with β thalassemia Major (TM) and β-thalassemia Intermedia (TI), considering left ventricular function.Results: The overall prevalence of PHT in TM and TI group was estimated to be 35.2% and 29.3%, respectively; while reduced LVEF was evident in 22.7% and 10.1% of patients with TM and TI, respectively. No significant correlation was observed between mean PAP and LVEF in the patients with TI (Pearson coefficient = -0.096, P value = 0.345); while, an adverse association was revealed between mean PAP and LVEF in patients with TM (Pearson coefficient = -0.227, P value = 0.033). Upon univariate analysis, the only significant association was observed between LVEF and pulmonary hypertension among TM patients (P value = 0.001).Our results did not indicate that male gender and aging may affect the development of PHT.Conclusions: According to our findings, a considerable proportion of patients with TM and TI may have PHT. We detected an adverse association between mean PAP and LVEF in patients with TM. Left ventricular function was reduced in patients with PHT among TM group.

Background: Alopecia areata (AA) is a common disease in the military population; however, a few studies have calculated the lifetime risk of alopecia areata in first-degree relatives of patients as well as the impact of stress. Objectives: The primary aim of this study was to calculate the lifetime risk of alopecia areata in first-degree relatives of index patients. The secondary aim of this study was to assess the role of stressful events in the onset/recurrence of disease. Patients and Methods: One hundred and twenty-one patients with alopecia areata and their first-degree relatives, which included 597 subjects in addition to 119 controls, were studied. We considered a gender and age-matched control for each patient. They were investigated for the occurrence of stressful events within the previous six months before the onset/recurrence of the disease. Results: More than twenty-six percent of patients had a positive family history, while 6.4 percent of first-degree relatives were affected by alopecia areata. Lifetime risks were estimated at 7.6% for parents, 9.9% for siblings, and 6.4% for children. Eighty-eight patients (73.9%) experienced stressful events within six months prior to the onset or recurrences of alopecia areata, while 32 subjects (26.9%) of the control group reported such events in the last six months (P value = 0.000). Conclusions: Calculated lifetime risks can be used in genetic counseling. It appears that stressful events can be considered to be contributing factors in the development of alopecia areata. Also, according to our results, the role of stress in the recurrence of alopecia areata is more prominent than the primary development of the disease.

BACKGROUND: Advances in the care of burn injuries have resulted from the efforts of regional patient-based specialist teams at burn care centers. OBJECTIVES: We conducted this study to assess the four-year epidemiology of burn injuries in Rasht, Iran. MATERIALS AND METHODS: In this cross-sectional study, medical records of 2274 burn patients, treated at Velayat hospital from January 2007 to December 2010 in Rasht, Iran, were assessed. Age, sex, level of education, occupation, severity and degree of burn, burn surface area, burn cause and outcome of patients were evaluated. RESULTS: In our study the overall mortality rate was 8.7%; 65.7% of patients were men and 34.3% were women. Mean age of patients was 31.47 ± 22.67 years. Mean Total Burn Surface Area (TBSA) was 15.24 ± 18.4. Lowest TBSA was 0.5% and highest TBSA was 100%. Significant associations were observed between age (P = 0.0001), place of residence (P = 0.004), level of education (P = 0.0001), unemployment (P = 0.0001), marital status (P = 0.021), causes of burn (P = 0.0001), TBSA (P = 0.0001) and mortality rate. In our study, no significant difference was observed between age and sex (P = 0.071). CONCLUSIONS: Due to high prevalence of burn injuries in Iran, increasing the level of awareness of the society as well as adhering to safety procedures both at home and workplace is recommended via implementing effective national safety policies. Language: en

The broad use of highly active anti-retroviral therapy (HAART), especially in developing world, has been associated with several problems such as lactic acidosis, lipodistrophy, pancreatitis, hyperlipidemia, insulin resistance and hepatotoxicity. Extensive use of HAART has also resulted in emergence of resistant HIV variants. Thereby, a pressing need for development of novel and cost-effective agents arises from these limitations. Setarud (IMOD™) is a safe, naturally- derived immunomodulator that was introduced for treatment of HIV patients in Iran. It is prepared as a mixture of herbal extracts including Tanacetum vulgare (tansy), Rosa canina and Urtica dioica (nettle) in addition to selenium, flavonoids and carotenes. Tanacetum vulgare may relieve anti-inflammatory symptoms and Rosa canina defers blood glucose and cholesterol elevation. Extracts from Urtica dioica may prevent maturation of myeloid dendritic cells and reduce T cell responses. A significant rise of CD4 count was observed in HIV patients treated by IMOD™ in clinical trial phases, which could be explained by its immunomodulatory effects. Anti-oxidative activity of compounds in IMOD™ might play a role in the clinical outcomes of patients treated with this drug. Moreover, IMOD™ may show improving activity upon lipid profile and liver metabolism. According to studies on IMOD™, it seems that IMOD™ has minor side effects. IMOD™ with international publication number WO 2007/087825 A1 is an herbal extract which includes Rosa canina, Urtica dioica, Tanacetum vulgare, and selenium comprising a treatment by pulsed electromagnetic field of high frequency and is useful in treatment of HIV infection and AIDS.

We present a 35-year-old man with history of Kawasaki disease who referred with myocardial infarction, and angiography, revealing aneurysm of left main and left anterior descending coronary arteries. The patient underwent percutaneous coronary intervention and thrombectomy and was discharged after 6 d. Coronary artery sequels of Kawasaki disease should be considered as one of the underlying causes of acute myocardial infarction in young adults.

We report a 45-year-old man with antroseptal myocardial infarction who developed bilateral basal alveolar infiltrates after initiating the fibrinolytic therapy. Although thrombolytic therapy with streptokinase is generally used in the course of acute myocardial infarction and has diminished morbidity and mortality, pulmonary hemorrhage is an uncommon, but a potentially life-threatening complication that should be regarded as one of the differential diagnoses of pulmonary infiltrates or dropping hemoglobin with no apparent bleeding site.

e20039Background: Carfilzomib (Ky) is an irreversible proteasome inhibitor. Phase III trials, ASPIRE and ENDEAVOR reported cardiovascular adverse events (CvAE) associated with Ky. We performed this...

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.

Objective To identify the frequency of syphilis among Iranian HIV-positive patients. Methods A cross-sectional study on the prevalence of syphilis and HIV co-infection among 450 patients diagnosed with HIV infection was conducted between 2004 and 2008 at Imam Khomeini hospital, Tehran, Iran. The lab tests including CD4 cell count, cerebrospinal fluid, veneral disease research laboratory (VDRL), fluorescent treponema antibody-absorption (FTA-Abs) and viral load were performed for all the patients. Data regarding medical history and their demographics were also collected. Results Of all 450 HIV-positive patients, 24 (5.3%) had a positive VDRL test and only two men had a FTA-Abs positive test which means 0.45% of them had a definite co-infection of syphilis. 65.3% of the HIV-positive patients were injection drug users that the co-infection prevalence of them was 0.7%. We did not find any patient with neurosyphilis. Conclusions Considering the increasing prevalence of HIV and also extensive use of highly active antiretroviral therapy in developing nations, the diagnosis of syphilis should be timely established using screening tests among such patients.