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Introduction Behcet's disease (BD) is a systemic inflammatory disease with various presentations. The data on the course of BD in Egyptian patients are limited. Objectives The objective of the study was to describe the evolution and association of the different phenotypes of BD. Material and methods This chronological cohort study included adult Egyptian patients suffering from BD. Demographic data and the chronological order of the disease's manifestations were collected. Results The study included 233 patients. Their mean age at the onset of the disease was 26.3 ± 6.9 years. The mean duration from onset of the disease to meeting the criteria was 11.2 ± 30.3 months. The mean duration of the disease was 96.8 ± 72.2 months. On onset of the disease, the most common phenotypes were mucocutaneous (84.5%), musculoskeletal (15.9%), ocular (14.6%) and peripheral venous disease (PVD) (7.3%); on the other hand, pulmonary, peripheral arterial and great vessel phenotypes evolved several years after onset of the disease. The mean time from meeting the criteria to the evolution of a new phenotype was 53.8 ± 58.7 months. Associations between the different phenotypes were observed: PVD and superficial thrombophlebitis, peripheral arterial disease and PVD; another association was also observed between aortic involvement and cerebrovascular disease. Conclusion BD could continue to evolve several years after onset of the disease, making the previous belief about BD yield questionable. BD tends to respect the anatomy of the affected system. Some phenotypes tend to coexist, suggesting a shared aethiopathogeny and that the disease is of a systemic nature.

Background. Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. The autoimmune regulator (AIRE) is a master regulator of self-tolerance development. AIRE mutations lead to the development of autoimmune polyglandular syndrome type 1 while AIRE polymorphisms have been linked to organ-specific autoimmunity. The study is aimed at addressing the association between AIRE polymorphisms, rs2075876 (G > A) and rs760426 (A > G), and SLE susceptibility and expression in Egyptian patients. Methods. Ninety-nine patients were included. One hundred and ten, and 123 control subjects were genotyped for rs2075876 and rs760426, respectively. Lupus severity was assessed using the Lupus Severity of Disease Index and Lupus Severity Index (LSI). Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index was considered. Genotyping was done using StepOne Real-Time PCR. Results. AIRE rs760426 GG was more frequent in the patients under the genotype level (14.1% vs. 4.9%, p = 0.032 ) and recessive model (14.1% vs. 4.9%, p = 0.017 , OR = 3.2 (1.2-8.7)). Musculoskeletal involvement and nephritis were associated with AIRE rs2075876 under the dominant (97.9% vs. 80.8%, p = 0.009 , OR = 11 (1.3-89.2)) and recessive models (100% vs. 69.3%, p = 0.032 ), respectively; and both were linked to AIRE rs2075876 at the allelic level: 98.3% vs. 85%, p = 0.005 , OR = 10.1 (1.3-76.6) and 82.8% vs. 68.6, p = 0.041 , OR = 2.2 (1-4.7), respectively. Patients with AIRE rs2075876 A alleles had a higher damage index ( 1 ± 1.3 vs. 0.6 ± 1.1, p = 0.045 ) while the LSI was greater in patients with AIRE rs2075876 (8.5 ± 0.5 vs. 7.8 ± 1.3, p = 0.002 ) and rs760426 (8.6 ± 11 vs. 7.8 ± 1.2, p = 0.031 ) under the recessive models. Conclusion. AIRE rs760426 could share in SLE susceptibility while AIRE rs2075876 could influence the disease expression and burden in Egyptian patients.

Background: Immune checkpoint inhibitors with or without chemotherapy form the backbone of treatment for patients with advanced NSCLC without an actionable driver mutation. Emerging literature shows that ICIs increase the risk of venous thromboembolism (VTE), which is a major cause of death in patients with NSCLC. The mechanism is yet to be elucidated but is likely secondary to inflammation. Since chemotherapy is immunosuppressive, we sought to understand if the addition of chemotherapy to ICIs impacted the incidence of VTEs. Methods: We performed a retrospective cohort study to evaluate thromboembolic outcomes in patients diagnosed with advanced NSCLC between 2012 and 2018 and treated with either ICIs or chemo immunotherapy at Cleveland Clinic Foundation. Diagnosis of thrombotic events (TE) (arterial/deep vein thrombosis and/or pulmonary embolism) was confirmed by imaging. Overall survival (OS) was estimated by Kaplan-Meier and compared using log rank test. Odds of developing TE was estimated and compared between ICI and ChemoIO groups, using Fisher's Exact Test. Results: A total of 367 NSCLC patients (242 pts on ICI only and 125 pts on ChemoIO regimen), were identified with a median age 65 years ( range 58-72), 52% were men, 82% white, 85.3% smokers, 91.8% had ECOG ≤2, 73 % had adenocarcinoma and 18% had squamous cell carcinoma, 34% with brain metastasis and the distribution of PDL1expression was as follows- 0.05). Conclusion: Rates of TE were high in patients with advanced NSCLC who received ICI therapy, but no different if treated with ICIs alone or ChemoIO. Further studies to better understand the pathophysiology of TE in patients treated with ICIs might allow us to identify subgroups of patients that are at the highest risk for TEs. Citation Format: Doaa Attia, Ran Zhao, Alok A. Khorana, Prandya Patil. Risk of thromboembolism in patients with non-small lung cancer (NSCLC) treated with immune check point inhibitors (ICIs) versus chemoimmunotherapy (ChemoIO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3217.

This study presents the elaboration and characterization of un-doped and Copper co-doped Zinc-Tin-Zirconiate (3, 6, 9 mol.%). Cux-ZTZr(2-x) nanostructured thin films prepared using sol-gel Copper co-doped Zinc Tin method on a glass substrate and annealed at 500oC for 1hr. The synthesized film samples are characterized by X-ray (XRD), scanning electron microscopy and energy dispersive X-ray (HR-SEM/EDX), Fourier transform infrared spectroscopy (FTIR), and UV–VIS–NIR double beam spectrophotometer. The experimental results demonstrated that all the prepared films exhibited a polycrystalline nanoparticle structure, and the crystallites size was found to be ranged from 17 and 32 nm. SEM micrographs showed scattered nanoparticles with irregular distribution over the substrates, and the particles size is in the range of 21–29 nm. The highly transparent (>85% for doped sample) nanostructures films show a bandgap increment from 4 to 4.19 ev with rising Copper content in zinc Tin Zirconiate. The effect of Cu focus in ZTZr will differ in the optical properties of the semiconductor, which means that these films have many advantages in solar cell application.

Background: Letrozole is an aromatase inhibitor with conflicting studies reporting its effects on memory in male and female animals, and whether the observed memory impairments become exacerbated with an additional insult such as Alzheimer's disease (AD); an illness in which beta-amyloid and hyperphosphorylated Tau (p-Tau) protein accumulate. We examined Letrozole effects on memory, hippocampal p-Tau and histopathology in animals treated with Letrozole only or on top of induced AD, and investigated whether there would be any sex-based differences in memory status and/or p-Tau.Methods: 51 adult male and female Sprague Dawley rats were divided into: Control groups: Intact, Letrozole Vehicle, CSF, and CSF+Letrozole Vehicle, Letrozole group, Streptozotocin (STZ) group; with induced AD via cerebroventricular STZ injection in artificial CSF and, STZ+Letrozole (STZ-L) group. Memory was tested in a T-maze to measure alternation percentage. Hippocampal p-Tau protein levels were estimated using ELISA, and histopathology was documented in sections stained with Hematoxylin and Eosin.Results: There were significant reductions in alternation percentage in the STZ, Letrozole and STZ-L groups; most severe in the STZ-L group and least severe in the Letrozole group. Significant elevation in p-Tau concentration was observed in the STZ, Letrozole and STZ-L groups compared to the controls. No differences were found between males and females in all groups in any of the studied parameters. Histopathological examination showed neurodegeneration and inflammation in the Letrozole, STZ and STZ-L groups. Conclusion: Letrozole alters memory, more so in experimentally-induced AD, increases p-Tau and may cause hippocampal pathological changes, with no sex-based differences.

Several studies have emphasized poor pregnancy outcomes associated with active lupus nephritis at the onset of conception. A few controversial studies have compared pregnancy outcome in patients with inactive lupus nephritis at conception and those without a history of lupus nephritis. This study aimed to find out if quiescent lupus nephritis at the onset of conception carries an increased risk of pregnancy complications compared to pregnancies without a history of lupus nephritis. This is a prospective cohort study carried out at the Rheumatology/Obstetrics Conjoint Clinic of Kasr Al-Ainy Hospital between January 2006 and December 2017. A total of 119 pregnancies were included: 72 pregnancies in group I (with a history of lupus nephritis) and 47 pregnancies in group II (non-renal systemic lupus erythematosus). They were subjected to full history taking, monthly clinical examination and laboratory investigations. In total, 16 (22.2%) renal pregnancies had renal flares at the onset of conception. Maternal complications, specifically renal flares, were reported in 36 (50%) pregnancies in group I and 13 (27.7) pregnancies in group II, with a significant difference ( p = 0.015). No significant differences were found concerning the frequency of pregnancy-related maternal and fetal complications between the two groups. When data were re-analyzed after excluding patients experiencing renal flares during the 6 months preceding pregnancy, there were no significant differences regarding the frequency of maternal and fetal complications between renal and non-renal pregnancies. In conclusion, lupus nephritis, per se, is not a risk factor for poor pregnancy outcome; rather, it is the lupus nephritis activity at the onset of pregnancy.

Background Interstitial lung diseases are common features in scleroderma that seem to add to the morbidity and mortality of the disease. Other complications that may occur with scleroderma are pulmonary hypertension. Aim to evaluate the functional status of patients with progressive systemic sclerosis-associated diffuse parenchymal lung disease. Methodology A total of 44 adult patients with a confirmed diagnosis of scleroderma were included. The disease severity was assumed by using the grading of the inter-incisor distance and finger-to-palm distance. Assessment of the chest high-resolution computed tomography (HRCT) was performed, and then functional assessment in the form of arterial blood gas, spirometry, 6-min walk distance, and echocardiography was performed. Results There were no significant differences between the scleroderma with diffuse parenchymal lung disease and those with normal HRCT regarding the measured and calculated parameters, except for the pulmonary artery systolic pressure, which was significantly higher in the normal HRCT group than those with interstitial lung disease.

Let-7 microRNAs may contribute to neurodegeneration, including Alzheimer's disease (AD), but, they were not investigated in Streptozotocin (STZ)-induced AD. Letrozole increases the expression of Let-7 in cell lines, with conflicting evidence regarding its effects on memory. This study examined Let-7 microRNAs in STZ-induced AD, their correlation with memory and hyperphosphorylated Tau (p-Tau) and the effects of Letrozole on them. Seven groups of adult Sprague Dawley rats were used: Intact, Letrozole, Letrozole Vehicle, STZ (with AD induced by intracerebroventricular injection of STZ in artificial CSF), CSF Control, STZ + Letrozole (STZ-L), and CSF + Letrozole Vehicle. Alternation percentage in T-maze was used as a measure of working memory. Let-7a, b and e and p-Tau levels in the hippocampus were estimated using qRT-PCR and ELISA, respectively. There were significant decreases in alternation percentage and increase in p-Tau in the STZ, Letrozole and STZ-L groups. Expression levels of all studied microRNAs were significantly elevated in the Letrozole and the STZ + L groups, with no difference between the two, suggesting that this elevation was due to Letrozole. Negative correlations were found between alternation percentage and the levels of all studied microRNAs, while positive ones were found between p-Tau concentration and the levels of studied microRNAs. These findings support the theory that Letrozole aggravates pre-existing lesions and add to the evidence of Let-7 neurotoxicity.

Aims. Neuropathic pain following nerve injury does not respond well to most available pharmacological remedies. We aimed to compare the outcome of the addition of adipose-derived mesenchymal stem cells (ADMSCs) to pregabalin for neuropathic pain treatment. Methods. Adult female albino rats ( n = 100 ) were randomized to receive traumatic sciatic nerve injury or sham. Animals were then randomized to ADMSC treatment with or without pregabalin. We conducted a battery of neurobehavioral and electrophysiological to assess neuropathic pain. Following sacrifice, we evaluated the histological changes and gene expression of brain-derived neurotrophic factor (BDNF) in the sciatic nerve. Serum and sciatic nerve tissue pro- and inflammatory cytokine levels were also assessed. Results. (1) All treatments significantly improved thermal withdrawal latency, sciatic nerve conduction velocity, and proinflammatory cytokine levels in injured animals, with no significant effect of the combined treatments compared to pregabalin monotherapy ( p < 0.05 each). (2) Combined treatment significantly improved medial gastrocnemius electromyographic amplitude and sciatic function index compared to pregabalin monotherapy ( p < 0.05 each). (3) Combined treatment significantly increased the BDNF expression, decreased anti-inflammatory cytokine ( p < 0.05 each), and restored the structural nerve damage, compared to pregabalin monotherapy. Conclusions. Combined treatment is associated with greater improvement of the sciatic nerve structure and function. Further studies are warranted to study the mechanism of action of the combined treatment to improve neuropathic pain.

Objectives Sexual dysfunction in systemic lupus erythematous (SLE) patients is an important issue to be tackled. We aimed to study the prevalence of sexual dysfunction in SLE women and detect its association with depression, functional disability and quality of life. Methods This study included 94 SLE females. Ninety-eight control females agreed to participate. Patients and controls answered a written form of the Arabic version of the Female Sexual Function Index (FSFI), Beck Depression Inventory (BDI), Health Assessment Questionnaire–Disability Index (HAQ-DI) and Short Form 36 (SF-36). Disease activity and damage were assessed using the SLE Disease Activity Index and the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. Results The frequency of sexual dysfunction was similar in the patients and control groups (77.7% versus 82.7%) while the BDI, HAQ-DI and SF-36 scores were significantly worse in SLE patients. SLE patients with and without sexual dysfunction differed in neither disease characteristics nor disease activity and damage indices. The FSFI showed a strong positive correlation with SF-36, and strong inverse correlations with BDI and HAQ-DI in the patients group while it had a weaker positive correlation with SF-36 and no correlations with the other two indices in the control group. Conclusion No significant difference was found in the prevalence of sexual dysfunction between SLE patients and controls. Sexual dysfunction in SLE patients is mostly related to depression, poor functional status, increased pain, poor health perception and bad quality of life. Neither disease activity nor damage contributes significantly to sexual dysfunction in lupus females.

BCL6 corepressor like-1 (BCORL1) mutation has rarely been described in thyroid cancer or in association with BRAF mutations in any malignancy. However, we report a 49-year-old woman who had aggressive follicular variant papillary thyroid carcinoma (FV-PTC) with both the BRAF K601E and BCORL1 mutations. The patient underwent a total thyroidectomy for a 3.6 cm right thyroid nodule and a smaller lesion in the left lobe in 2007; both were FV-PTCs with no lymphovascular invasion or metastases. In 2015, a positron emission tomography–CT scan showed a small defect in the left posterior lateral fifth rib with mild increased hypermetabolic activity with standardised uptake value of 3.9 and another lesion in the right hip at the junction of the femoral neck and trochanter. Tumour biopsy and genetic analysis revealed an uncommon BRAF K601E and a rare BCORL1 mutation. While rare, we report a case of aggressive FV-PTC with both the BRAF K601E and BCORL1 mutations.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease. Cyclophosphamide (CYC) is a cytotoxic drug of a narrow therapeutic window that is commonly used in lupus nephritis (LN) treatment. However, 30-40% of patients experience CYC resistance. CYC inactivation is mediated by the glutathione S transferases (GSTs) superfamily: GST class A (GSTA) has the greatest activity and contains 5 isoenzymes. Polymorphisms of genes involved in the drug metabolism could alter the drug pharmacokinetics and effectiveness. CYC pharmacokinetics and pharmacogenomics are extensively studied in malignancies; however, scarce data are available about this issue in the autoimmune rheumatic diseases. Prediction of the drug response helps the achievement of the highest benefit-to-risk ratio. The aim of this case-control study was to address the association between GSTA1 polymorphism (-69C T, rs3957356), and the rate of response to and side effects of intravenous CYC in LN patients.Ninety-four patients were included and divided into matched groups: resistant and responsive. Genotyping was performed using restriction fragment length polymorphism method after amplification.A significant association between the TT genotype, and CYC resistance and partial response was observed. Concerning the recessive model, none of the patients within the TT group achieved complete remission. CYC side effects were more common with the polymorphism under the genotype, recessive model, and allele distributions. When patients' pre- and post-treatment characteristics were compared, patients with the TT genotype did not show any significant improvement.LN patients with GSTA1 (-69C T, rs3957356) TT genotype have the highest risk of CYC unresponsiveness and toxicity. Key-Points • LN patients with the wild genotype of GSTA1 have the greatest probability of achieving a complete renal response to IV CYC. • The homozygous GSTA1 (-69C T, rs3957356) TT genotype is associated with the highest risk of LN unresponsiveness to IV CYC. • The homozygous GSTA1 (-69C T, rs3957356) TT genotype is associated with the highest risk of CYC-related side effects.

Purpose: Maxillofacial injuries are commonly encountered in the practice of emergency medicine. More than 50% of patients with these injuries have multisystem trauma that requires coordinated management between emergency physicians and surgical specialists in oral and maxillofacial surgery, otolaryngology, plastic surgery, ophthalmology, and trauma surgery. The aim of this study is to identify the patterns of brain injuries associated with maxillofacial trauma and its outcome. Methods: This descriptive study (cross-sectional) was carried out among 90 polytrauma patients with maxillofacial fractures attending the Emergency Department at Suez Canal university Hospital and fulfilling our inclusion and exclusion criteria. Results: This study demonstrates the relation between type of maxillofacial fracture and type of traumatic brain injuries in which the majority of patients with epidural hemorrhage presented with mid face fractures (60%), while the minority of them presented with upper and lower face fractures (20% for each of them). The majority of patients with subdural hemorrhage were associated with mid face fractures (75%), the majority of patients with brain contusions associated with mid face fractures (75%), and all of the patients presented by pneumocephalus were associated with mid face fractures (100%). Conclusion: The results of this study confirm the value of quick diagnosis and early intervention, which is fundamental to prevent morbidity as well as mortality especially with regards to prevention of traumatic brain injury as even a short duration of hypoxia and edema will lead to significant permanent neurological deficits. Keywords: Maxillofacial fractures, Brain injuries, Outcome

Background Several peritoneal dialysis catheter (PDC) placement techniques have been described. The objective of this study was to compare the fluoroscopy and ultrasound guidance technique with the laparoscopic technique. Methods We retrospectively reviewed the medical records of 260 patients who had their first PDC placed between January 2005 and June 2016. We compared the outcomes of the fluoroscopic and ultrasound-guided catheter placement technique (radiologic group, n = 50) with the laparoscopic catheter placement technique (laparoscopic group, n = 190). The primary endpoint was complication-free catheter survival at 365 days. Secondary endpoints were complication-free catheter survival at 90 days, overall catheter survival at 90 and 365 days, median days to first complication and median days to catheter removal. Results In the radiologic group, the complication-free catheter survival at 90 and 365 days was 64% and 48%, respectively, while in the laparoscopic group it was 71% (P = 0.374) and 53% (P = 0.494), respectively. Catheter malfunction was significantly higher in the laparoscopic group (30%) compared with the radiologic group (16%, P = 0.048). The overall catheter survival at 90 and 365 days was 76% and 52%, respectively, in the radiologic group, while in the laparoscopic group it was 88% (P = 0.0514) an 48% (P = 0.652), respectively. There was no significant difference in the median days to first complication and the median days to catheter removal between the two groups (P = 0.71). Conclusion The technique of fluoroscopic and ultrasound-guided PDC placement is a clinically effective and safe alternative to laparoscopic catheter placement with similar survival and complication rates.

Background: The relationship between venous thromboembolism (VTE) and lymphoma is well established. In recent years, direct oral anticoagulants (DOACs) have been adopted as a treatment option for cancer associated thrombosis, however the majority of data using DOACs is in solid tumor patients. Here, we report the risk of recurrent VTE, bleeding outcomes, and effect of VTE on survival among lymphoma patients treated in a large centralized cancer associated thrombosis clinic. Methods: We prospectively followed lymphoma patients referred to our clinic from 8/2014-01/2021. VTE events including deep venous thrombosis (DVT), pulmonary embolism (PE), and visceral vein thrombosis (VVT), were noted. Overall survival (OS) was estimated by Kaplan-Meier and compared using log rank test. Cumulative incidence rate of VTE was estimated and compared using Gray's method. Results: A total of 103 patients were referred to our clinic due to clinical suspicion of VTE, of whom 40 (38.8%) were diagnosed with an acute VTE. The median age of the study population was66 (range 19-88), 61.2% were male and 16.5% had prior VTE. Non-Hodgkin Lymphoma (NHL) compromised 87.4%, with diffuse large b-cell lymphoma (DLBCL) being the most common subtype. Most patients had stage 4 disease (55.34%), had high grade lymphoma (defined as grade 3-4) (51.46%), and were on antineoplastic treatment (71.67%) at the time of VTE diagnosis. Site of VTE was DVT in 35.9%, PE in 5.8%, both DVT and PE in 2.9% and VVT in 0.97% of patients. Of these, 21 (20.39%) received a (DOAC), 14(13.59%) received enoxaparin, and 2(1.94) had IVC filter placed due to contraindication to anticoagulation. VTE recurrence occurred in 10% patients (total n=4; 2 were on enoxaparin and 2 were on rivaroxaban). Cumulative incidence of VTE in all patients at 6 months was 1% (95% CI: 0-2.9%), at 1 year was 3% (95% CI: 0-6.4%) with no significant difference in VTE or bleeding rates between lymphoma types or grade groups (P >0.05) (Table 1). Of 37 patients on anticoagulation, 10.8% experienced bleeding events (n=4) , of which 1 (2.7%) had major bleeding on IVC filter and 3 (8.1%) had CRNMB (2 on enoxaparin and 1 on rivaroxaban) at 6 month follow-up. Median follow-up was 35.9 months (range: 0.4-77.7 months) and median 2 year OS was 76%, 95% CI (68-85%). Overall survival was negatively impacted by age (patients over age 65 had a 2 year OS rate of 67%95% CI (0.56-0.81), p=0.01). Lymphoma grade had no impact on OS (2-year OS rate= 0.69, 95% CI (0.57-0.84), P=0.1132) Conclusion: High grade and low grade lymphoma patients treated in our centralized cancer thrombosis clinic had a 10% chance of VTE recurrence when treated with DOAC or enoxaparin. Bleeding rates were low in both groups; however, we saw decreased overall survival in those treated with DOACs. This data adds to the growing knowledge of treating hematologic malignancies with direct oral anticoagulants, but larger studies are needed to study the safety and efficacy of these agents in lymphoma patients. Figure 1 Figure 1. Disclosures Khorana: Halozyme: Consultancy, Honoraria; Anthos: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bayer: Consultancy, Honoraria. Angelini: Sanofi: Membership on an entity's Board of Directors or advisory committees.

Background: Thromboembolism (TE) in cancer significantly contributes to morbidity and mortality. Cancer immunotherapy is linked to several inflammatory immune mediated adverse events. Inflammation plays a key role in thrombosis but the association between immunotherapy and venous thromboembolism (VTE) has not been thoroughly investigated. Here, we report the incidence of thromboembolism in patients with lung cancer treated with immune checkpoint inhibitors (ICIs). Methods: A single institution retrospective cohort of 514 adult patients with lung cancer who received ICIs (pembrolizumab, nivolumab, atezolizumab, ipilumab, avelumab) between 2013 and 2017 was included. Diagnosis of VTE (deep vein thrombosis and/or pulmonary embolism, and visceral vein thrombosis "VVT") was confirmed by imaging. Overall survival (OS) was estimated by Kaplan-Meier and compared using log rank test. Cumulative incidence rate of VTE was estimated and compared using Gray's method. Results: Of 514 patients (pts), 58.75% were males, 83.27% were white with a median age of 67 (range 22-91). Nivolumab was most commonly used (52.14%), followed by Pembrolizumab (30.16%), Atezolizumab (10.89%), combination of ipilimumab plus nivolumab (6.61), ipilimumab (2.33%), Avelumab (1.17%). 88.52% had stage 4 disease at treatment initiation. VTE events occurred in 62 pts (12%) (3.5% DVT, 4.47% PE, 2.72% both, 0.97 VVT, 0.19 VVT + PE, 0.19% VVT+DVT+PE). The cumulative incidence rate of VTE of all pts at 6-month and 1-year post IO was 7.6% (95% CI:5.3-9.9%) and 11.6% (95% CI:8.7-14.6%) respectively. The rate of survival without VTE at 6 months after IO treatment was 91% (95% CI: 89-94%). None of the following factors (age, gender, race, cancer staging, IO type or line) were significantly associated with time-to-VTE (TTVTE) survival post treatment (P >0.05). Median OS of all pts was 12.6 months (95% CI: 11.0-16.7 months), with 2-year OS rate of 35% (95% CI: 31-41%). Conclusion: ICIs in lung cancer are associated with higher VTE risk within six months and a year of initiation of treatment. Further studies are needed to investigate the risk factors for ICIs-associated VTE. Disclosures Pennell: Astrazeneca: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; G1 therapeutics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Genentech: Consultancy, Honoraria; Mirati Therapeutics, Inc.: Consultancy, Honoraria; Viosera Therapeutics: Consultancy, Honoraria; Eli Lilly: Consultancy, Honoraria; BMS: Consultancy, Honoraria. McCrae: Sanofi, Novartis, Alexion, and Johnson & Johnson: Consultancy, Honoraria; Dova, Novartis, Rigel, and Sanofi Genzyme: Consultancy. Khorana: Pfizer: Consultancy, Honoraria; Anthos: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Halozyme: Consultancy, Honoraria; Bayer: Consultancy, Honoraria.

Introduction: Multiple myeloma accounts for 1% of all cancers and approximately 10% of all hematologic malignancies. With the advent of novel therapies for multiple myeloma and emerging data from randomized trials, there has been a substantial improvement and favorable outcomes in survival. Here, we report demographics and outcomes in a cohort of patients who underwent Autologous Stem Cell Transplant (ASCT) over the past year. Methods: In this retrospective, cohort study, we assessed all MM patients who received ASCT from January 1, 2020, to January 15, 2021, at Cleveland Clinic, and followed until July 31, 2021. Baseline demographics, ECOG performance status, ISS stage, cytogenetic risk category, therapy received before ASCT, maintenance therapy, time to first relapse/progression, time to next treatment (TTNT; 2nd line of treatment onwards) with treatment response (defined per IMWG response criteria) before and after ASCT were obtained by review of electronic medical records. All patients received HDCT Melphalan 140 mg/m2 or 200 mg/m2 prior to ASCT. Continuous variables were presented as median and interquartile range, while categorical variables were presented as numbers and percentages. Categorical variables were compared using the chi-square test. Results: Of 81 MM patients who underwent ASCT, 59% were males, 84% were white, with a median age of 62 (IQR: 57-67) at the time of diagnosis. 42 (52%) and 24 (30%) patients belonged to the standard and high-risk category. Amongst high-risk cytogenetic abnormalities, +1q was the most common (72%) followed by del(17p) (28%). Baseline characteristics of patients are included in Table 1.1. Lenalidomide, bortezomib, and dexamethasone (VRd) regimen was the most common (75%) first-line induction regimen used, followed by Daratumumab-based regimens (20%). 10 (12%) patients required second-line treatment, and 6 (7%) patients required more than 2 lines of treatments prior to transplant. The median time to transplant was 6.5 months. The overall response rate (ORR) prior to transplant was 99% (21% complete (CR), 40% very good partial (VGPR), and 38% partial (PR)). The ORR post-ASCT was 78% (CR 27%, VGPR 37%, PR 14%). There was no significant difference in response between risk categories after transplant (P=0.72). At 1-year follow-up, 10 (12%) patients had relapsed and 7 (9%) patients had progression of the disease. 3 (4%) patients died of progressive MM, one of which had progressed to plasma cell leukemia. Response to treatment before and after the ASCT are summarized in Table 1.2 and Figure 1. The time to second-line treatment among patients with relapse/progression was 7 months [IQR: 3.75-10.25]. Conclusion: Here we report the demographics and outcomes of patients with MM undergoing modern modality treatments and ASCT, at our center over the last year. The median time to transplant was 6.5 months after induction therapy, and the ORR post-ASCT was 78%. No significant difference in response was observed between high and standard risk categories. No transplant-related mortality was observed as well. Figure 1 Figure 1. Disclosures Anwer: Allogene Therapeutics: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding; BMS / Celgene: Honoraria, Research Funding; GlaxoSmithKline: Research Funding.

Ascending aortic pseudoaneurysms (AO PSAs), if left untreated, are complicated by a high rate of rupture resulting in significant morbidity and mortality. New transcatheter modalities have emerged as acceptable surgical alternatives for their management. We present a case of an ascending aortic PSA in which intraoperative two- and three-dimensional transesophageal echocardiography (2DTEE and 3DTEE) provided a comprehensive assessment of the PSA in pre- and postclosure settings.

Purpose: The study aimed to evaluate and correlate between the levels of vascular endothelial growth factor (VEGF) in serum and aqueous humor in cases of neovascular glaucoma (NVG) to stand up on if it can be used as a marker for early detection of such cases. Methods: This observational case control study included 60 eyes, divided into 3 groups, group A of 30 eyes presented by cataract of different causes (not diabetic patients and no signs of NVG) as a control group and group B of 30 eyes with NVG due to different causes, group C of the same eyes in group B but after one month of treatment by intravitreal bevacizumab and laser treatment by pan retinal photocoagulation (PRP). Serum VEGF was estimated in all groups, also aqueous humor VEGF was estimated in group A and B only. In addition glycosylated hemoglobin (HbA1c) was estimated in group B; statistical analysis of the results was performed. Results: The study revealed that the commonest cause of NVG was proliferative diabetic retinopathy (PDR) in 26 cases (86.7%), HbA1c in group B revealed mean value 7.68% ± 2.75%. Serum VEFG level in the group B of cases of NVG was significantly higher than the control group A (P 0.05). Conclusions: VEGF is considered a good marker for the NVG either in serum or aqueous humor, laser treatment and the use of anti-VEGF are crucial treatment for such cases, and also glycemic control is a must for regulation of the vascular process in diabetic patients for prevention of such ocular neovascularization.

Purpose: To study the role of C-reactive protein (CRP) in the progression of diabetic retinopathy before and after treatment to determine if it can be used as a biomarker for progression or regression. Methods: This observational case study included 90 persons divided into 4 groups: group A of 30 normal persons (non diabetic) as a control group, group B of 30 diabetic patients without retinopathy, group C of 30 untreated patients with proliferative diabetic retinopathy (PDR) and group D of the same patients of group C after 3 months of laser treatment by pan retinal photocoagulation (PRP). Serum CRP protein was measured in all groups, interpretation of results was applied. Results: The study revealed that serum CRP level increased significantly in patients with PDR (group C) in comparison to both groups of normal control persons (group A) and diabetic patients without retinopathy (group B) (P 0.05). Also the same finding was noticed in elderly patients above 50 years. Conclusion: CRP is considered a biomarker for PDR even in older age patients, but not a good indictor used for follow up patients after treatment.

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A central venous catheter is the most common access for initiating hemodialysis. Prolonged access through a central venous catheter increases the risk of infection and dysfunction of the catheter with potential development of catheter-induced thrombosis and embolism. However, fracture and dislodgement of the catheter with subsequent embolization is an unexpected complication. Endovascular treatment is a promising method to remove intravascular foreign bodies. We herein report a case of a 58-year-old woman undergoing prolonged hemodialysis who required central venous catheter removal because of mechanical fracture of the tunneled cuffed catheter and its migration in the internal jugular vein. An urgent chest X-ray showed that the two free ends of the fractured tunneled cuffed catheter were located in the right atrium and right internal jugular vein. Phlebotomy of the internal jugular vein was successfully performed to retrieve the fractured tunneled cuffed catheter and the associated thrombi. In this case, phlebotomy for retrieval of the embolized catheter fragment extending into the right atrium was a safe alternative to an endovascular technique of catheter fragment retrieval. Phlebotomy preserved the integrity of the catheter fragment and its associated thrombus and was both cost-effective and safe.

Background: The treatment paradigm for cancer associated thrombosis (CAT) has evolved over recent years from using low molecular weight heparin (LMWH) to direct oral anticoagulants (DOACs). Some randomized trials suggest decreased rates of recurrent venous thromboembolism (VTE) in CAT patients treated with DOACs compared to LMWH but also reported increased rates of bleeding. The Cleveland Clinic Taussig Cancer Center has been treating cancer thrombosis in a centralized CAT clinic since 2014. Here we report our rates of bleeding and recurrent VTE in cancer patients treated with anticoagulation. Methods: We prospectively followed cancer patients referred to our clinic from 8/2014-10/2019. A total of 1548 patients were referred to the clinic, of whom 462 were diagnosed with an acute VTE. VTE events, including deep venous thrombosis, pulmonary embolism, and visceral thrombosis, were noted. The comparison of bleeding rates (defined using ISTH criteria for major and clinically relevant non major bleeding, CRNMB) among treatment groups (LMWH vs DOACs) was examined using chi-square test. Rate of recurrent VTE was analyzed using a competing model in which death was treated as a competing risk. Results: The study population comprised 462 patients with acute VTE with a mean age of 62.67±12.23 and 51.8 % males. Of these, 234 (52.9%) received LMWH, 161(36.4%) received DOACs, and 47 (10.6%) received other agents including warfarin for initial anticoagulation. Overall, the 6-month, 1 year, and 2-year VTE recurrence rate was 5.9%, 6.6%, 7.9%, respectively. Recurrent VTE rates were similar for LMWHs, DOACs and other agents (P>0.05). Of 368 patients for whom follow-up data was available, 74 (16.7%) had bleeding event , of which 25 (33.8%) had major bleeding and 49 (66.4%) had CRNMB at 6 month follow-up with no difference across three treatment groups (p=0.56). Conclusion: In this real-world practice setting, rates of recurrent VTE and bleeding were similar for DOACs and LMWH suggesting that with careful patient selection the concern for higher bleeding with DOACs in cancer patients can be safely overcome. Disclosures McCrae: Momenta Pharmaceuticals: Consultancy; Novartis: Honoraria; Rigel: Consultancy; Dova: Consultancy. Khorana:Merck: Research Funding; Medscape: Honoraria; Leo Pharma: Honoraria; Seattle Genetics: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Janssen: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; BMS: Honoraria, Research Funding; Leap: Research Funding.

Introduction: In recent years, direct oral anticoagulants (DOACs) have been adopted as a treatment option for cancer associated thrombosis (CAT). Randomized trials comparing anti-Xa drugs to low molecular weight heparin (LMWH) showed treatment with DOACs conferred less risk of recurrent venous thromboembolism (VTE), but found higher rates of clinically important bleeding, especially in patients with gastrointestinal (GI) malignancies. Given these findings, there is a need for additional data regarding the safety of DOAC use in GI malignancies. Here, we report bleeding events of GI cancer patients treated with anticoagulation in a large centralized CAT clinic. Methods: We evaluated a prospective cohort of patients referred to our CAT clinic from 8/2014-10/2019. Patients with primary gastrointestinal malignancies treated with therapeutic anticoagulation with LMWH or a DOAC for acute VTE were included. Bleeding was defined using the ISTH criteria for major and clinically relevant non-major bleeding (CRNMB). Bleeding rates were compared between luminal [anus/anal, colon, esophagus, rectal, stomach] and extraluminal GI cancers [gallbladder, liver/bile duct, and pancreas]. Patient characteristics associated with bleeding were evaluated with Fisher's exact test and the association of age with bleeding was analyzed by Wilcoxan rank sum test. Results: Of 463 patients with acute VTE, 73 patients (15.8%) with primary GI tumors were included in the analysis. Males comprised 57.5% of the population, median age was 62 (range 36-86), and 61.6% had stage 4 disease. Figure 1 shows a breakdown of tumor types. Enoxaparin was the most commonly used anticoagulant (n=48, 65.8%), followed by DOAC (n=25, 34.2%). Overall, 16 (21.9%) patients had a bleeding event within 6 months of treatment (7 major bleeds and 9 CRNMB). There was no difference in 6-month bleeding rate between patients treated with LMWH (n= 9, 18.8%) vs. DOAC (n=7, 28.0%), p=0.39. None of the clinical factors analyzed were significantly associated with bleeding (Table 1). There was no difference in bleeding rate in patients with luminal GI cancers vs. extraluminal GI cancers and no difference was found in a three-way association between site, treatment, and bleeding, p=0.40 (Table 2). Conclusions: In our centralized cancer thrombosis clinic, patients with GI malignancies had similar rates of major and CRNMB when treated with LMWH or DOAC. In both cohorts, bleeding rates were high within 6 months of starting anticoagulation. There were no statistically significant differences in bleeding rates based on several clinical characteristics evaluated in this study. Although limited by a small patient population, this study adds to the knowledge of treating GI malignancies with DOACs. There is a need for further prospective evaluations regarding the safety of DOAC use in GI cancer patients and there remains an unmet need for antithrombotic treatments that do not increase bleeding potential. Disclosures McCrae: Novartis: Honoraria; Momenta Pharmaceuticals: Consultancy; Rigel: Consultancy; Dova: Consultancy. Khorana:Bayer: Honoraria; Pharmacyte: Honoraria; Pharmacyclics: Honoraria; Array: Other: Research funding (to institution); Merck: Research Funding; Leap: Research Funding; BMS: Honoraria, Research Funding; Seattle Genetics: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Medscape: Honoraria; Leo Pharma: Honoraria; Janssen: Honoraria.

Background:Patients with cancer are at high risk of both venous thromboembolism (VTE) and arterial events, however, little is known about the association between venous and arterial thromboembolic events in patients with cancer. In this study, we evaluated the incidence and relative risk of subsequent arterial thromboembolism in patients with a confirmed diagnosis of acute cancer-associated VTE. Methods:We conducted a retrospective cohort study at the Cleveland Clinic Taussig Cancer Institute of cancer patients with confirmed VTE who were referred to a centralized thrombosis clinic between January 2017-October 2019 with at least 6 months of follow-up. Arterial thrombotic events (ATE), including myocardial infarction, peripheral arterial thrombosis, and ischemic stroke, were identified by manual review of electronic medical records. The cumulative incidence rate of each ATE event was calculated. Results:The study population comprised 294 patients with a median age of (63.5) years (range 27-90), and 49.7 % were male. The cumulative incidence rate of overall ATE during the 6-month, 1-year, and 2-year follow-up period was 3.07%, 3.42%, and 3.42%, respectively. A total of 10 patients who experienced arterial events of whom 7 had ischemic stroke, 2 had myocardial infarction, 2 had peripheral arterial thrombosis where one patient had two arterial events of myocardial infarction and peripheral arterial thrombosis(Table 1 shows the incidence rates of arterial events). Amongst patients with ATE, 30 % were active smokers (n=3), 90% had hypertension (n=9), 20% had diabetes mellitus (n=2), 50% had a family history of coronary artery disease (n=5), 40% were on statin and daily aspirin use (n=4), 40% were obese with BMI >30 (n=4). 40% of ATE patients(n=4) were on a therapeutic anticoagulant therapy at the time of arterial thrombotic event (3 on enoxaparin, 1 on apixaban) Conclusion:Cancer patients with acute VTE have a substantial increased risk of subsequent arterial thromboembolism particularly in the first six months after VTE. Ischemic stroke was the most frequent arterial event and ATE events occured despite therapeutic anticoagulation in a large subset of our cohort. Further prospective studies are needed to better understand the risk of ATE in cancer patients, and further studies should be designed to mitigate the risk of arterial events in this patient population. Disclosures McCrae: Momenta Pharmaceuticals:Consultancy;Novartis:Honoraria;Rigel:Consultancy;Dova:Consultancy.Khorana:Pharmacyclics:Honoraria;Pharmacyte:Honoraria;Seattle Genetics:Honoraria;Leo Pharma:Honoraria;Medscape:Honoraria;Sanofi:Honoraria;Pfizer:Honoraria;Bayer:Honoraria;Janssen:Honoraria;Array:Other: Research funding (to institution);Merck:Research Funding;BMS:Honoraria, Research Funding;Leap:Research Funding.

7558 Background: Prolymphocytic leukemia (PLL) compromises two subsets; B-cell and T-cell, accounting for less than 2% of mature lymphocytic leukemia. Both of them are rare lymphoid neoplasms with a very aggressive clinical course and poor prognosis. Methods: We used SEER program dataset between 1998 and 2016. We divided the patients into 2 groups: B-PLL and T-PLL and identified them using ‘ICD-O-3 histology recode: 9833/3 and 9834/3 respectively. We used SPSS software (version 26, IBM, NY, USA) to calculate overall survival using Kaplan-Meier methods and compare the survival between the two subtypes using the log-rank test. We also used multivariable covariate-adjust cox models to determine the impact of age, sex, race, cause of death, and associated primary malignancies on survival in both types. Results: A retrospective cohort study of 783 patients (295 B-PLL and 488 T-PLL) with overall survival rate of 22.5% (30.2% B-PLL and 18% T-PLL). The overall median survival for PLL was 16 months (95 CI, 13.745-18.255). The median survival of B-PLL (25 months, 95%CI, 15.733-34.267) was much better than T-PLL (14 months, 95%CI, 11.922-16.078). The mean age was 68.7±15.3. Patient age was an independent factor in determining the survival and inversely associated with survival time in both types (p < 0.0001). The survival rate was worst ) among age groups older than 79, between 70-79 years (8.9%, 18.9%) respectively. Although white male patients were more affected in both types, neither sex nor race significantly affected survival (P 0.554, 0.062 respectively). 64.7% of PLL patients died due to cancer. Patients with cancer-related death had significantly shorter survival time in both T-PLL group (HR = 0.351, 95% CI 0.241-0.512) and B-PLL group (HR = 0.682, 95% CI 0.491-0.945). We also found that 24.4% of B-PLL and 19% of T-PLL patients have another associated primary malignancy. Among hematological malignancies, non-hodgkin lymphoma was the commonest. Although associated solid tumors were less common, Prostate cancer and breast cancer were the commonest for both types and lung/bronchus malignancies were more associated with T-PLL. Conclusions: T-PLL subtype has worse prognosis. Age is the most important independent predictor of survival in both types. Although most of affected patients were white males, race and gender have no impact on survival. Non-hodgkin lymphoma is the commonest primary associated malignancy followed by breast and prostate cancer in both types.

Introduction Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can vary among different ethnic and racial groups. Objective The objective of this paper is to study the prevalence of various manifestations of SLE in a sample of the Egyptian population. Patients and methods Information in this study was derived from the medical records of SLE patients who sought medical advice at a private clinic in Cairo from January 1980 to June 2016. Results This study included 1109 SLE patients, of whom 114 (10.3%) were males and 995 were females (89.7%). Mean age of onset was 25.89 ± 10.81 years, while the median of disease duration from the onset of the disease till the last recorded visit was 26 months. The most common cumulative manifestations were arthritis (76.7%), malar rash (48.5%), leukopenia (45.7%), and photosensitivity (45.6%). A total of 33.1% of the patients had nephritis, and neuropsychiatric lupus was present in 6.4% of the patients. Secondary antiphospholipid syndrome was present in 11.5% of the patients. Antinuclear antibody and anti-double-stranded deoxyribonucleic acid were present in 1060/1094 (96.9%) and 842/1062 (79.3%) of the patients, respectively. Antiphospholipid antibodies were present in 266/636 (41.8%) of the patients, anti-Smith in 54/240 (22.5%), anti-SSA/Ro in 61/229 (20.4%), and anti-SSB/La in 32/277 (11.6%) of the patients. Male patients had a statistically higher prevalence of nephritis ( p = 0.01), whereas arthritis and alopecia were statistically higher in females ( p = 0.012 and p = 0.006, respectively). Patients with juvenile onset had a statistically higher prevalence of nephritis and seizures ( p 0.001 and p = 0.012, respectively). Conclusions Arthritis and malar rash represented the most common clinical manifestations. Male and juvenile-onset patients had a predilection toward a more severe disease. These results are in agreement with many studies conducted in the Middle East and worldwide. On the other hand, major organ involvement was exceptionally low, which is contradictory to several reports from the Middle East and across the globe.

Background Tenofovir disoproxil fumarate (TDF) may cause acute kidney injury and proximal tubular dysfunction. However, no detailed studies document urinary phosphate wasting as a marker of TDF-induced tubulopathy. Methods Records of HIV-infected patients with presumed TDF toxicity were reviewed. We describe the characteristics and clinical course of 15 patients who had documented elevated (>20%) fractional excretion of phosphate (FEphos). Results Patients were predominantly Caucasian and male (73 and 80%, respectively), with a mean age of 56 years (range 38–76). Of the 15 patients, 11 had a estimated glomerular filtration rate (eGFR) of >90 mL/min/1.732 at time of TDF initiation. The mean duration of TDF therapy prior to diagnosis of TDF toxicity was 64 months. Mean FEphos was 34% (range 20–62). The mean eGFR at TDF initiation was 104 mL/min/1.73 m2 [standard deviation (SD) 17.0] with a gradual decline to 69 mL/min/1.73 m2 (SD 19.0) by the time of TDF discontinuation. Of 10 patients with repeated FEphos after TDF discontinuation, 9 had improvement of their FEphos. Of these individuals, 6 had normalization of their FEphos. Estimated GFR improved in 12 patients after discontinuation of TDF, though importantly, none returned to their baseline eGFR. Conclusions Urinary phosphate wasting is a sensitive marker for TDF-induced proximal tubulopathy and is associated with unrecognized and permanent renal function decline. Tubular dysfunction can develop after years of TDF therapy in those with normal kidney function at the time of drug initiation. This suggests that continuing vigilance be maintained in all those on TDF.

Hagerty, et al. [10] conducted the 1st prospective cohort study about the role of preoperative finasteride for 25 patients given finasteride for about 2-4 months and 50 controls without treatment. They followed both groups for 4 months and found that only 8.3% of patients underwent preoperative treatment experienced perioperative bleeding while 37% of the control group got bleeding during the operation. So, they concluded that preoperative finasteride decreases the bleeding rate, postoperative complication such as clot retention especially in Abstract

Background and aims Systemic lupus erythrematosus (SLE) is an autoimmune disease with a myriad of manifestations, that could vary among different ethnic and racial groups. Aim of the study: To study the prevalence of various manifestations of SLE in an Egyptian population. Methods Information in this study was derived from the medical records of SLE patients, who followed up in 2 private clinics in Cairo from January 1980 to June 2016. Results This study included 1109 SLE patients, of which 114 (10.3%) were males and 995 were females (89.7%). Age of onset showed a mean of 26±11.19 years, and the mean of disease duration was 48.78±58.46 months. The most common manifestations were synovitis (76.7%), malar rash (48.5%), leukopenia (45.7%), and photosensitivity (45.6%). At least one of the antiphospholipid antibodies was present in 41.8% of the patients, with thromboembolic manifestations and/or recurrent fetal loss present in 18.3% of the patients. Neuropsychiatric manifestations were evident in 7.8% of the patients, with seizures being the most common neuropsychiatric manifestation, present in 4%. 33.1% of the patients had nephritis, which succeeded the onset of the disease by a mean duration of 20±21.3 months. 29.3% of the patients continued follow up and received induction therapy according to the guidelines at the time of presentation (cyclophosphamide: 11.8%, mycophenolate mofetyl: 7.6%, and azathioprine: 9.8%). Of which, 24.9% continued follow up and achieved partial (9.9%) and complete (15%) remission. Conclusions Synovitis and malar rash were the most common manifestations in our study. Secondary antiphospholipid was present in 18.3% of the patients.