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While the relative efficacy of remdesivir as a therapeutic agent in selected patients with COVID-19 has been established, safety concerns have been raised regarding potential nephrotoxicity and hepatotoxicity. Our main objective was to investigate the kidney- and liver-related safety outcomes in patients with COVID-19 treated with remdesivir in a public hospital in New York. A propensity score-matched retrospective study was conducted in hospitalized patients with COVID-19 from 1 June 2020 to 10 March 2021. A total of 927 patients were included in this study (remdesivir: 427, non-remdesivir: 500; women: 51.8%; median age 61 years; median BMI: 28.5 kg/m2). Matching without replacement yielded a cohort of 248 patients (124 in each group). In the matched cohort, the remdesivir group had a significantly lower rate of acute kidney injury (AKI) (12.1% vs. 21.8%, p = 0.042), a lower rate of acute liver injury (ALI) on the verge of statistical significance (7.3% vs. 14.5%, p = 0.067), and non-significantly lower death rate (13.7% vs. 16.1%, p = 0.593) compared to the non-remdesivir group. Multivariable analyses revealed that patients treated with remdesivir were found to be associated with a significantly lower likelihood for AKI (OR: 0.40; 95% CI: 0.24–0.67, p < 0.001), no association was found for ALI (OR: 0.68; 95% CI: 0.35–1.30, p = 0.241), while a trend towards an association of patients treated with remdesivir with a lower likelihood for in-hospital death was observed (OR: 0.57; 95% CI: 0.32–1.01, p = 0.053). In conclusion, no safety concerns with regards to renal and liver outcomes were raised in patients with COVID-19 treated with remdesivir. Instead, there were signals of possible nephroprotection and improved in-hospital mortality.

e18561 Background: Prostate cancer is the second leading cause of cancer-related mortality among males in the United States after lung cancer. Among other factors, physical access to clinical trial site plays a pivotal role in the recruitment process and hence impact outcomes. We aim to study the geographical distribution of phase III and IV prostate cancer clinical trials in the United States. Methods: The United States Cancer Statistics Data Visualisation Tool was utilised to estimate the number of new cases of prostate cancer for the latest available years i.e., 2014-2018. An extensive search was carried out at ClinicalTrials.gov registry using advanced search fields – disease (prostate cancer), sex (male), study type (clinical trial), phase (III and IV), country (United States) and study start (from 01/01/2014 to12/31/2018). The trials which were terminated, withdrawn, or suspended were excluded from the study. Both these tools were further explored to provide state-wise distribution of new trials and cases. Results: Between 2014-2018 in the United States, 997, 454 new prostate cancer cases were reported and 59 phase III & IV clinical trials were made available across 51 states. The average number of new prostate cancer cases and trials per state was 19,558 and 17 (range 45-0) respectively. The states with maximum reported number of new cases were California, New York, Florida, and Texas. These accounted for 30.2% of total cases and only 15.5% of total trials. The states with least reported new cases were Alaska, Vermont, Wyoming, and North Dakota. These accounted for 0.84 % of total cases and 2% of total trials [Table]. The states with the minimum number of trials per case were Mississippi (0.00035), Texas (0.00041), Florida (0.00042), New York (0.00045) and California (0.00047) whereas the states with maximum number of trials per case were Alabama (0.2352), District of Colombia (0.0061), Alaska (0.0054) and Vermont (0.0024). Conclusions: Variation in the availability of phase III and IV clinical trials for newly diagnosed prostate cancer cases was noted across 51 states of the US during the study period from 2014-2018. The states with higher disease burden had a much lower ratio of trials available per case despite higher absolute number of clinical trials in comparison to the states with lower disease burden. This highlights the need for better geographical allocation of clinical trials in the future based on the cancer burden for efficient resource utilisation and improved healthcare delivery.[Table: see text]

Disorders of color variation can be localized or generalized, congenital or acquired, acute or chronic. Among the various causes of generalized skin darkening encountered in the pediatric age group, acquired universal melanosis aka Carbon Baby Syndrome is an uncommon hypermelanotic condition, with a histologic appearance of extensive epidermal melanization. The authors report one such case of a 4-year old boy with progressive darkening of skin starting at the age of 1 year and involving the entire body surface in the absence of any other systemic alterations. The disease prevalence, etiology, mechanism and prognosis are still unknown.

Pulmonary hypertension is one of the difficult situations to treat. Complex pathophysiology, association of the multiple comorbidities make clinical scenario challenging. Recently it is being shown that patients who had recovered from coronavirus disease infection, are at risk of developing pulmonary hypertension. Studies on animals have been going on to find out newer treatment options. There are recent advancements in the treatment of pulmonary hypertension. Role of anticoagulation, recombinant fusion proteins, stem cell therapy are emerging as therapeutic options for affected patients. SGLT2 inhibitors have potential to have beneficial effects on pulmonary hypertension. Apart from the medical managements, advanced interventions are also getting popular. In this review article, the authors have discussed pathophysiology, recent advancement of treatments including coronavirus disease patients, and future aspect of managing pulmonary hypertension. We have highlighted treatment options for patients with sleep apnea, interstitial lung disease to discuss the challenges and possible options to manage those patients.

Background Atypical HUS (aHUS) is a rare thrombotic microangiopathy (TMA) caused by complement dysregulation. Eculizumab is a humanized monoclonal antibody targeting against complement factor C5. Ravulizumab, a longer acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for treatment of aHUS in 2019. Here we describe the clinical presentation, laboratory, genetic profile, treatment along with long-term sequelae of patients diagnosed with aHUS. The outcomes of restrictive use of eculizumab and the use of ravulizumab were also studied. Materials and Methods We conducted a single center retrospective cohort study, searching electronic medical records of patients diagnosed and treated for aHUS at University of Arkansas for Medical Sciences, from January 1, 2013 to January 31, 2021, after IRB approval. Inclusion criteria :1) Presence of microangiopathic hemolytic anemia (MAHA) with thrombocytopenia 2) ADAMTS13 activity > 10 % 3) Age > 18. Exclusion criteria: 1) Age < 18 years 2) TMA associated with hemolytic uremic syndrome, scleroderma renal crises, anti-phospholipid syndrome. Results Seventeen patients meeting the inclusion criteria were enrolled in the study. The mean age at diagnosis was 47.4 ± 17.9 years. Most of the patients were Caucasians (n=10, 58%) and females (n= 14, 82%). All the patients except one had acute kidney injury (AKI) at presentation (n=16, 94.1%), the most frequent extra-renal presentation was CNS involvement -seizures, confusion and altered mental status (n= 7, 41.2 %) followed by Gastrointestinal- non-bloody diarrhea, nausea and vomiting (n=5, 29.4 %) [Figure 1]. Lab investigations are described in [Table 1]. Complement genetic testing was done in 100% of study population. Factor H related genes 1/3 (CFHR1/3) and complement factor H (CFH) were the most commonly found pathogenic mutations [Table 2]. In this study, pregnancy and infection (n= 4, 23.5% each) were identified as the most common triggers [Figure 2]. For two of the patients, it was the first pregnancy and for the other two, it was their second and third pregnancies. They presented at the second, sixth, and sixteenth week postpartum respectively. Eleven (64.70%) patients developed chronic kidney disease (CKD) with six (35.29%) patients progressing to end stage renal disease (ESRD). Two (11.76 %) pregnant patients developed cardiomyopathy, two (11.76%) patients developed pulmonary complications (pneumonia and pulmonary hypertension) and three (17.64%) patients developed epilepsy. All the postpartum females in our study were able to breastfeed while on eculizumab with no long-term complications in the neonates. One patient had two subsequent deliveries with no ante, intra, or post-partum consequences or repeated triggers of aHUS. Fourteen patients (82.3%) received therapeutic plasma exchange, four (23.5%) patients received iv methyl prednisone (1mg/kg) and two (11.7%) patients received IVIg prior to initiating eculizumab. Over time, five (29.41%) patients opted to completely stop drug therapy and four patients (23.52%) chose to shift to ravulizumab because of the ease of treatment duration (every 8 weeks rather than every 2 weeks for eculizumab). All these nine patients remained in remission with stable hematologic and renal parameters on subsequent follow-ups [Table 3]. Three patients (17.6 % mortality) died in our study due to causes unrelated to aHUS. Conclusions: The clinical diagnosis of atypical HUS can be challenging especially with extra-renal manifestations. Females were four times more affected than males. PCMs were present in 11 patients. Early diagnosis and treatment with C5 inhibitors improves morbidity and mortality. The decision to discontinue or switch eculizumab to ravulizumab will likely decrease healthcare costs and improve patient compliance but should be based on disease severity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

BACKGROUND Heavy chain diseases (HCDs) are B-cell neoplasms characterised by production of monoclonal (M) protein consisting only of immunoglobulin heavy chain without a bound light chain. Three types have been recognized- IgA alpha HCD (most common, a form of extra nodal marginal zone lymphoma of mucosal associated lymphoid tissue aka immunoproliferative small intestinal disease [IPSID], Mediterranean lymphoma or Seligmann disease], IgG gamma HCD (aka Franklin's disease, variant of lymphoplasmacytic lymphoma) and IgM mu HCD (rarest, resembles chronic lymphocytic leukemia). Limited data is available regarding the epidemiology, survival patterns, and incidence of second primary malignancies in patients with HCD in the Unites States. MATERIALS AND METHODS We performed a retrospective analysis using SEER* stat version 8.3.9 statistical software and November 2020 submission of SEER 18 registry which covers ~ 27.8 % of US population based on the 2010 census. We identified all cases > 1 years old diagnosed with Heavy chain disease between 2000 and 2018 using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code 9762/3. We analyzed survival using Kaplan- Meier method, and MP-SIR session was used to calculate the risk of second primary malignancy. RESULTS A total of 64 cases of HCD were identified. Most common primary sites of involvement were bone marrow (82.8%), lymph nodes (9.3%), GI tract (3.1%), others (4.6%)- spleen, blood and vertebral column. The crude, age-adjusted to 2000 US standard population and age-specific incidence rate of HCD in the United States is < 1/100,000 respectively. The median age at diagnosis is 68 years with incidence in males being about 1.3 times that of females. Bimodal age distribution was observed, with peak incidence between ages 60-64 and 75-79 [Figure 1]. In our entire cohort, 82.8% (n=53) patients were Caucasians, 15.6 % (n=10) patients were African Americans, and 1.5% (n=1) patients were American Indian/Alaska Native. Among Caucasians, 56.6% (n=30) patients were males, and 43.3% (n=23) patients were females. Between 2000-2018, the maximum cases (n=7 each) were diagnosed in the year 2002 and 2008 [Figure 2] The median overall survival for the entire cohort was 48 months (95% CI: 35- 61). Overall survival rates of all ages, sex and race at 1 year, 2 year and 5 years were found to be 86.1%, 71.4%, 57.8% respectively. OS at 5 years declines after 70 years .Patients with HCD are at risk of developing subsequent solid and haematological malignancies within 5 years of diagnosis. 9 (14 %) cases developed SPMs: urinary bladder (n=1), lung and bronchus (n=2), Hodgkin-nodal (n=1), Non-Hodgkin Lymphoma -extra nodal (n=1), GI cancers [stomach (n=1), esophagus (n=1) and ascending colon (n=1)], miscellaneous (n=1). [Figure 4]. The mean follow-up duration for new SPM was 51 months. Overall, 39 patients died: 3 (4%) from miscellaneous malignant cancer and 11 (17%) patients from haematological malignancy; the most common being Non-Hodgkin lymphoma (n=8), followed by Hodgkin lymphoma (n=1), Multiple myeloma (n=1) and leukemia (n=1). CONCLUSIONS HCD is an extremely rare haematological malignancy. The incidence of HCD is proportionately higher among Caucasians as compared to other races, with no reported case among Asian or Pacific Islanders. Among Caucasians, males and females have approximately equal risk of acquiring HCD. Most patient die because of their primary haematological malignancy. We recommend close follow-up for at least the first 5 years after initial diagnosis. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

INTRODUCTION Aggressive NK-cell leukemia ( ANKL) is a systemic lymphoproliferative disorder of natural killer (NK) cells frequently associated with Epstein-Barr virus (EBV) which has been grouped under histiocytic/dendritic neoplasms in the 2008 WHO classification of hematopoietic neoplasms. Due to rarity of diagnosis, the current available literature is limited to case reports and case series. This population-based study using Surveillance Epidemiology and End result program (SEER) is the largest to explore demographic characteristics, survival patterns and long-term outcomes in patients with ANKL in the United States. MATERIALS AND METHODS We utilized SEER 18 November 2020 submission database to select all patients (> 1 years of age) diagnosed from 2000-2018 with ANKL using International Classification of Diseases for Oncology edition 3 (ICD-O-3) code of 9948/3. Patients were divided into various cohorts based on age (80 years), sex, race (Caucasians, African American, Asian/Pacific islander and American Indians/Alaska natives) and median household income of county of residence (< $ 50,000 vs > $50,000). We used SEER*stat to calculate age adjusted incidence rate using 2000 US standard population. Kaplan Meier curve was utilized to calculate 5-year overall survival. Cox proportional hazard model was used for multivariate analysis of factors associated with survival and p RESULTS A total of 140 patients were identified with ANKL. The median age at diagnosis is 58 years. The crude, age-adjusted to 2000 US standard population and age-specific incidence rate of HCD in Unites states is < 1/100, 000 respectively. The incidence in males is 1.9 times that of females- 92 males (65.7%) and 48 females (34.2%). Between 2001-2018, minimum number of cases were diagnosed in 2010 (n=2).Out of the cohort, 107 patients were White (76.4%), 21 patients were Asian or Pacific islander (15 %), 9 patients were African Americans (6.4%) and 3 patients were American Indian/Alaska native (2.1%). The median overall survival was 7 months (95% CI; 0-16). Survival rates at 1year, 2 years and 5 years were found to be 45.3% , 37.1 % and 31.1% respectively [Figure 1]. 5 year overall survival rates are as follows- Whites ( 69.7% ), Blacks ( 63.1%), American Indian (59.9%), Asian or Pacific Islander ( 66.8%). On multivariate analysis, black race was associated with poor outcomes (p 0.008), whereas sex, income and age had no significant effect on cancer outcomes. CONCLUSIONS Our study shows that ANKL is a rare hematological malignancy in general population with a poor median survival of less than one year. Males are twice more likely to be affected than females with poor outcomes in africo-americans. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

We report a case of a 55-year-old known hypertensive female who presented with features suggestive of dementia, which, on further workup unveiled background dyslipidemia and type 2 diabetes mellitus. An magnetic resonance imaging of the brain revealed findings suggestive of Binswanger's disease. This is a discussion of this unusual disease and its presentation and the differentials of this presentation which may be encountered in general clinical practice.

Background: Psoriasis is an immune-mediated chronic inflammatory dermatosis with a complex interplay of environmental and genetic factors. Among the various documented triggers, drug-related psoriasis constitutes a distinct entity with exposure resulting in either induction or exacerbation of psoriasis. Here we describe the case of a 45-year-old female with telmisartan aggravated chronic plaque psoriasis previously well controlled on oral methotrexate.

Ankylosing Spondylitis (AS) is a chronic progressive inflammatory spondyloarthropathy typically involving the axial skeleton, especially the sacroiliac joints and spine. Genetic predisposition in AS leads to its common association with certain extra-articular diseases-anterior uveitis (25-30%), psoriasis (10%) and inflammatory bowel diseases (50%). Cardiorespiratory involvement in AS is rare and is usually present in long standing disease as restrictive lung disease, conduction abnormalities or aortic insufficiency. Here, we present a case of unusual AS in a 32-year-old non-smoker male with a major involvement of peripheral joints along with spine and chronic obstructive lung disease with apical fibro-bullous cavity and right sided heart failure over a short duration of disease course. His condition was acutely stabilised with diuretics, anti-hypertensive drugs, anti-pyretics, antibiotics and oxygen inhalation followed by maintenance on Non-steroidal anti-inflammatory agents. Hence, in a patient of AS, a strong index of suspicion should be there for both usual and unusual extra-articular manifestations and a complete work-up would help in early diagnosis and treatment.

The clinical presentation of a young woman with galactorrhoea is described in detail including the history and clinical examination findings. While the patient and her family members feared a serious medical condition which had so far been an obscurity despite a number of investigations, we tried to diagnose the patient starting from the basics, which after a proper history revealed a levosulpiride-induced galactorrhoea. This again lays emphasis on the old adage in medical field that 'a proper history and examination are the key to diagnosis'. There are few reports pertaining to levosulpiride-induced galactorrhoea making it a rare side effect of this drug. We further try to discuss the different causes of galactorrhoea in a young non-pregnant woman which can be encountered in clinical practice.

Adenolipoma of the thyroid gland is a rare benign neoplasm composed of normal thyroid and mature adipose tissue. Ordinarily, only a small amount of fat exists in a normal thyroid gland. CT and MRI may differentiate between benign and malignant lesions, and fine-needle aspirate often assists diagnosis. Surgical excision for adenolipoma is considered curative. We report the case of a 67-year-old man presenting with a large neck lump and evidence of airway obstruction. Imaging revealed a 97 × 70 mm left thyroid mass with retropharyngeal extension and laryngotracheal compression. Hemithyroidectomy was performed with subsequent histology confirming a large thyroid adenolipoma. The patient's symptoms resolved and he remains asymptomatic with no sign of recurrence 2 years postsurgery.

Descending necrotizing mediastinitis is a rare complication of upper respiratory infections. A quick diagnosis and prompt and complete surgical drainage is important for a successful outcome. A 74-year-old man with descending necrotizing mediastinitis needed a sternotomy, multiple washouts, and delayed sternal closure.

Bioprosthetic valves are implanted in elderly patients with good follow up results. The degeneration of these valves is slow and there are multiple aetiologies for that. It is unclear whether renal failure accelerates the degeneration of bioprosthetic valves in patients with normal calcium levels. We present a case with tissue valve degeneration 16 months postoperatively in a patient with renal failure.

C Z o ut right upper limb images revealed a distal occlusion f brachial artery. She underwent a successful brachial mbolectomy under local anaesthesia with a patch angiolasty. Her dissection was managed conservatively with trict blood pressure control. A further CT scan done n day 10 showed no evidence of dissection. Patient was symptomatic at this stage and on good blood pressure ontrol. Type A aortic dissections are most often managed with urgical repair. Feldman et al. [1] have reported that medcal management is to be considered for high risk cases. hey have reported that if the presentation is after 48 h of hest pain then there is no significant difference between urgical and medical management in 10 years although he trend points to better survival in surgical group. Such onclusions have been reached by other like Chan et al 2]. In our institute we almost always consider surgery nless the risks are too high. This type of type A dissecion is very uncommon [3]. This patient was stable after

Thymomas rarely present with chest pain due to hemorrhage. This could cause shortness of breath if it ruptures into the pleural space, and is best managed surgically. We describe the case of an 83-year-old woman who presented with such symptoms. Computed tomography showed a ruptured mediastinal mass with pleural effusion. She was managed successfully by thoracotomy with excision of the mass and drainage of the effusion. Histopathology revealed a ruptured thymoma with infarction and necrosis.