Multiple Admissions Research Articles

Non-convulsive epiletic seizure after electroconvulsive therapy session

IntroductionElectroconvulsive therapy (ECT) is a procedure performed under general anaesthesia involving triggering an intentional brief seizure through small electrical currents through the brain. The anaesthetic depth should be adequate prior to shock and measured with BIS, a processed electroencephalogram (EEG) monitor. Adjusting the hypnotic dose allows to decrease the ictal threshold and thus improve the response to treatment and decrease side effects.ObjectivesOur goal is detecting elements such as spontaneous epileptiform activity after ECT without tonic-clonic activity with the spectral density matrix (SDM).MethodsOur patient: an 87-year-old woman, diagnosed with F20.2 catatonic schizophrenia and under antipsychotic treatment since her youth. She has required multiple hospital admissions due to psychopathological decompensations until starting monthly maintenance ECT sessions in 2014. Since then she no new hospital admissions have been required.ResultsImages 1D and 1E shows the SDM, a spectrogram of the EEG. The X axis show time (minutes), the Y axis shows the frequency (Hz) and the Z axis shows the energy or intensity of that electrical activity in the frequency bands replaced by colors: warm colors (red) reflecting high intensity electroencephalographic activity and cool colors (yellow, blue and green), low activity. Images 2 and 3’s EDM shows spontaneous epileptiform activity after electroconvulsive therapy without tonic-clonic activity. We observed an initial EDM of an awake patient, with warm colours in practically all frequency bands, including the beta band (13-30 Hz), characteristic of waking states. Around 9:50 anaesthetic induction occurs, activity increases in slow frequencies (red colours in alpha, theta and delta), plus an increase of cold colours in beta, reflecting the disappearance of brain activity in that frequency. The asterisk reflects the EEG response to the electrical discharge, followed by a postcritical state with brain activity exclusively in slow waves and high amplitude (delta and some theta) and absence of activity in other frequencies (blue colour in the beta and alpha bands) around 9:57. At about 10:00 there is an abrupt appearance of high intensity brain activity (warm colours) in beta and alpha and delta, mainly, reflecting spontaneous epileptiform activity after treatment and clinically reflected as a patient absent and disconnected from the environment, but without tonic-clonic activity. New postcritical state in which blue colour predominates, reflecting little brain activity, and warmer colours reappear in all frequency bands, including beta, reflecting the progressive recovery of wakefulness.Image:Image 2:Image 3:ConclusionsPsychiatric pathology can be reflected in the SDM, which allows to observe changes in the EEG, correcting the electrical stimulus of the shock and the dose of anesthetic appropriate to the patient to trigger an intentional brief seizure under general anesthesia.Disclosure of InterestNone Declared

I don’t know where I’m going or where I come from. Self-disorders in schizophrenia.

IntroductionIn the early stages of schizophrenia the person experiences feelings of strangeness about themselves, difficulty in making sense of things and difficulty in interacting with their environment. Based on this, self-disorder assessment instruments have been developed and empirical studies have been conducted to assess people at risk of developing a schizophrenia spectrum disorder. These studies show that self-disorders are found in pre-psychotic stages and that their manifestation can predict the transition to schizophrenia spectrum disorders.ObjectivesWe present the case of a patient with multiple diagnoses and mainly dissociative symptoms who, after years of evolution, was diagnosed with schizophrenia.MethodsBibliographic review including the latest articles in Pubmed about self-disorders and schizophrenia.ResultsWe present the clinical case of a 51-year-old woman with a long history of follow-up in mental health consultations and with multiple hospital admissions to the psychiatric unit, with several diagnoses including: dissociative disorder, histrionic personality disorder, adaptive disorder unspecified psychotic disorder and, finally, schizophrenia. The patient during the first hospital admissions showed a clinical picture of intense anxiety, disorientation and claiming to be a different person. The patient related these episodes to stressors she had experienced, and they improved markedly after a short period of hospital admission. Later, psychotic symptoms appeared in the form of auditory and visual hallucinations and delusional ideation, mainly of harm, so that after several years of follow-up and study in mental health consultations and in the psychiatric day hospital, she was diagnosed with schizophrenia and treatment with antipsychotics was introduced, with a marked clinical improvement being observed.ConclusionsIt is important to take into account this type of symptoms (self-disorders), as they allow the identification of individuals in the early stages of the disorder and create the opportunity for early therapeutic interventions.Disclosure of InterestNone Declared

Silent Screams; Lily's Story

Silent Screams; Lily's Story Eva V. Regel "Trauma is personal. It does not disappear if it is not validated. When it is ignored or invalidated, the silent screams continue internally heard only by the one held captive. When someone enters the pain and hears the scream, healing can begin." —Danielle Bernock, "Emerging Wings; A true story of Lies, Pain and the Love that Heals." Some patients stay with you long after they leave. They appear in your mind when you walk by the hospital room they occupied or when someone mentions their name. There is [End Page 19] something about the narrative of their life and illness that makes you hold on to them. Lily is one such patient for me. Lily was a 45-year-old paraplegic woman who was well known to many providers in the hospital. She had a complex trauma history (childhood physical and sexual abuse, intimate partner violence, domestic violence), homelessness, and multiple psychiatric admissions. In addition, she had a complex medical history, including chronic pain issues and substance use disorder. Many providers considered her to be a "very difficult" or "challenging" patient because she would "dictate" her care, had low distress tolerance and would have explosive angry outbursts requiring frequent visits from Police and Security. To top it off, after months of a challenging stay on a unit, she would eventually leave against medical advice. Everyone involved in her care felt that discharge to a safe setting such as a skilled nursing facility would be her best option. Yet, she was a very "hard" sell to any facility because of her behavioral issues, relatively young age, extensive history of drug use, and medication non-compliance. Even though the unit I worked in was familiar with "difficult" patients like Lily, the floor staff was anxious and concerned about the effect Lily would have on patients, staff, and providers. The combined anticipatory anxiety worsened after we were told that Lily left against medical advice three days before her admission to our unit as a reaction to the staff's attempt to develop a behavioral plan. I remember the day I met Lily. I was working as the clinical social worker on the floor, helping patients with adjustment to coping with hospitalization, addressing mental health issues that usually exacerbate in the acute care setting, and providing support to the staff caring for a psychosocially complex patient population. It was the second day after Lily arrived on the floor, and Police and Security had already come up three times. As I walked out of another patient's room, a bedside nurse stopped me in the hallway. "Can you please talk to her? … Please, just talk to her, or sit with her. I just need a break. I have been in that room since I started my shift. I am exhausted." The nurse had an exasperated and pleading look, and even though I was rushing to a meeting, I decided to meet with Lily instead. When I walked into her room, I saw a thin, small-framed woman with brown hair pulled back into a tight bun. She had freckles peppered all over her round face, neck, and chest. Her features were delicate and small, and her almond-shaped green eyes were her most prominent feature. She was wearing a white tee and jeans. She was sitting in her wheelchair; her makeup bag was lying on the table next to her. I introduced myself and my role on the team, trying not to stumble under a very heavy glare. "Tell them to leave me alone. That nurse is always in my room. Spying. I might not be able to walk, but I can still use my hands. I can call if I need help." And so I did. And when I came back, Lily and I talked a little about her life. And the next day, we talked a little more. And then again. Lily was giving me small glimpses of who she was and the events in her life. Then, one day, in the middle of the conversation about her day and telling me how much she hated to be confined to her hospital room, she looked...

Predicting Hepatotoxicity Associated with Low-Dose Methotrexate Using Machine Learning

An accurate prediction of the hepatotoxicity associated with low-dose methotrexate can provide evidence for a reasonable treatment choice. This study aimed to develop a machine learning-based prediction model to predict hepatotoxicity associated with low-dose methotrexate and explore the associated risk factors. Eligible patients with immune system disorders, who received low-dose methotrexate at West China Hospital between 1 January 2018, and 31 December 2019, were enrolled. A retrospective review of the included patients was conducted. Risk factors were selected from multiple patient characteristics, including demographics, admissions, and treatments. Eight algorithms, including eXtreme Gradient Boosting (XGBoost), AdaBoost, CatBoost, Gradient Boosting Decision Tree (GBDT), Light Gradient Boosting Machine (LightGBM), Tree-based Pipeline Optimization Tool (TPOT), Random Forest (RF), and Artificial Neural Network (ANN), were used to establish the prediction model. A total of 782 patients were included, and hepatotoxicity was detected in 35.68% (279/782) of the patients. The Random Forest model with the best predictive capacity was chosen to establish the prediction model (receiver operating characteristic curve 0.97, accuracy 64.33%, precision 50.00%, recall 32.14%, and F1 39.13%). Among the 15 risk factors, the highest score was a body mass index of 0.237, followed by age (0.198), the number of drugs (0.151), and the number of comorbidities (0.144). These factors demonstrated their importance in predicting hepatotoxicity associated with low-dose methotrexate. Using machine learning, this novel study established a predictive model for low-dose methotrexate-related hepatotoxicity. The model can improve medication safety in patients taking methotrexate in clinical practice.

Extraintestinal Clostridioides difficile Infection (CDI): A Recurrent Battle with Resilient Abdominal Wall Abscess.

Risk factors for extraintestinal CDI include prior hospital stay, prolonged antibiotic therapy, proton pump inhibitor (PPI) use, relative state of immunodeficiency such as malnutrition and diabetes mellitus, previous abdominal surgery especially following perforation and leak of intestinal content.Presentation can be late following surgery with mesh repair (foreign body implantation) for intestinal perforation as they have high risk of colonisation, which later leads to infection.For extraintestinal CDI in the presence of a foreign body, removal is the desired course of action. But it is not always possible given the presence of comorbidities in this population, thus resulting in a prolonged course of antibiotics.

Artritis séptica de rodilla por Serratia marcescens en paciente con hemofilia A

We present the case of a 24-year-old male patient with hemophilia A of 14 years of evolution. The patient presented recurrent hemarthrosis in the right knee, who developed septic arthritis in knee due to Serratia marcescens with a satisfactory response to intra-articular lavage with saline solution and 28 days of treatment whith carbapenems. In patients with septic arthritis, previous hemarthrosis and multiple hospital admissions, the presence of this germ should be suspected. The treatment is surgical and with broad-spectrum antibiotics.

Abstract TMP106: Decline In The Severity Of Hospitalized Ischemic Stroke 2005-2015: The Greater Cincinnati/Northern Kentucky Stroke Study

Background: Monitoring changes in ischemic stroke severity at the population level is important as changes in risk factors and clinical treatments could influence stroke severity. We describe trends in the distribution of NIHSS across 3 time periods in a population-based epidemiologic stroke study. Methods: In 2005, 2010, and 2015 all adult acute ischemic strokes occurring within the Greater Cincinnati area presenting to 15 hospitals were ascertained using discharge codes (ICD-9 433-436; IDC-10 I63-I68, G45-46). Following physician verification, confirmed ischemic stroke cases underwent chart abstraction including estimation of a retrospective (rNIHSS) score at presentation. Descriptive statistics (rNIHSS median, IQR) were generated by survey year, demographics, and medical history. Using a binary definition of stroke severity (median rNIHSS score &gt 4 versus &lt 4), multivariable logistic regression was used to estimate changes in stroke severity over time, adjusting for potential confounders. Random effects were used to account for multiple admissions occurring in the same subject. Results: The number of ischemic stroke admissions in the 2005, 2010, and 2015 surveys was 1778, 1903, and 1933, respectively (Table). The median (IQR) rNIHSS scores were 3 (2-7), 3 (1-6), and 2 (1-6) across the 3 surveys, respectively; the proportion of admissions with rNIHSS &gt 4 was 48%, 39% and 37%, respectively. After adjusting for demographics, medical history and pre-stroke function, compared to 2005, the odds ratio for more severe stroke was 0.69 (95% CI= 0.60-0.79, p=0.001) in 2010 and 0.63 (95% CI= 0.55-0.73, p=0.001) in 2015. Conclusions: In this population- based study there was a statistically significant change in the severity of ischemic stroke hospitalizations with increases in the proportion of milder strokes over time. Potential reasons for this change need to be explored but could include changes in risk factors, clinical treatments or diagnostic approach.

Anemia is a risk factor for rapid eGFR decline in type 2 diabetes.

To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes. This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis. The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine β2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline. Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

Ballistic Facial Trauma Reconstruction: Incidence and Practice Patterns in the Civilian Population.

Management of nonfatal ballistic facial trauma is well described in the literature for wounds secondary to military combat. However, there is little literature describing such management in civilian practice. We aimed to describe nonmilitary patients with recent nonfatal facial injuries from ballistic trauma using the California Office of Statewide Health Planning and Development patient database. A retrospective study was performed using the California Office of Statewide Health Planning and Development Ambulatory Surgery and Inpatient datasets. All adults with the International Classification of Diseases, 10th Revision codes of severe nonfatal facial trauma from firearms requiring emergent surgery during 2016-2018 were included. Outcomes assessed include number and type of facial procedures performed, hospital length of stay, number of admissions, timing of definitive management, and lifetime hospitalization costs. A total of 331 traceable patients were identified over this 3-year period. The average age was 35.4 years (SD, 15.2), and 87% were male. The median index admission length of stay was 8 days (interquartile range, 3-15 days). Subsequent readmission was required for 123 (37.2%) patients with 10% mortality in the index admission. Total median charges per patient for all admissions were $257,804 (interquartile range, $105,601-$531,916). A total of 215 patients (65%) had at least 1 facial repair performed. Of all 331 patients, 64.3% underwent musculoskeletal repair (n = 213), 31.4% underwent digestive system repair (n = 104), and 29.6% underwent respiratory system repair (n = 98). The average number of repairs per patient was 2.52 (SD, 3.38), with 35% not having any of the specified International Classification of Diseases, 10th Revision repair codes. A total of 27% of patients had 1 procedure performed, whereas 38% received 2 or more, for an average of 3.87 (SD, 3.5) repairs over the study duration. To our knowledge, this is the first assessment of civilian characteristics of nonfatal ballistic facial trauma in California. Nonfatal facial ballistic trauma results in complex injuries to multiple body systems, requiring long admissions, costly hospital stays, and coordination of care across several surgical specialties. Many patients require a variety of procedures over multiple admissions, highlighting the overall morbidity of these injuries. Future studies will look at how care for these patients differs between various hospitals and geographic regions and whether current civilian management aligns with well-defined military reconstructive protocols for facial ballistic injuries.

Impact of Vaccination on Cost and Course of Hospitalization Associated with COVID-19 Infection.

Examine the impact of vaccination status on hospital cost and course for patients admitted with COVID-19 infection. Retrospective cohort study characterizing vaccinated and unvaccinated individuals hospitalized for COVID-19 between April 2021 to January 2022. Large academic medical center. Patients were included if they were greater than 18 years old, fully vaccinated or unvaccinated against COVID-19, and admitted for COVID-19 infection. 437 consecutively admitted patients for COVID-19 infection met inclusion criteria. Of these, 79 were excluded for unknown or partial vaccination status, transfer from an outside hospital, or multiple COVID-19 related admissions. Overall, 279 (77.9%) unvaccinated patients compared to 79 (22.1%) vaccinated patients were hospitalized with a diagnosis of COVID-19. Average length of stay was significantly lower in the vaccinated group (6.47 days versus 8.92 days, P = 0.03). Vaccinated patients experienced a 70.6% lower risk of ICU admission (OR = 0.29, 95% CI 0.12-0.71, P = 0.006). The unadjusted cost of hospitalization was not found to be statistically significant ($119,630 versus $191,146, P = 0.06). After adjusting for age and comorbidities, vaccinated patients experienced a 26% lower cost of hospitalization compared to unvaccinated patients (P = 0.004). Unvaccinated patients incurred a significantly higher cost of hospitalization per day ($29,425 vs $13,845 P < 0.0001). Unvaccinated patients (n = 118, 42.9%) were more likely than vaccinated patients (n = 16, 20.3%) to require high-flow oxygen or mechanical ventilation (OR = 2.95, 95% CI 1.62-5.38, P = 0.0004). Vaccinated patients experienced a lower cost of hospitalization after adjusting for age and comorbidities and shorter length of stay compared to unvaccinated patients admitted for COVID-19.

Ileal Neuroendocrine Tumour Causing Carcinoid Syndrome in Absence of Hepatic Metastasis

Carcinoid syndrome consists of the classic symptom triad of flushing, diarrhoea, and valvular heart disease. It occurs in the majority of patients with liver metastases. This report presents a 68-year-old female who suffered from chronic diarrhoea with a history of multiple admissions for the same. On evaluation, a Computed Tomography (CT) scan showed a terminal ileal lesion and bulky ovaries. Suspecting Neuroendocrine Tumour (NET) with carcinoid syndrome, a Gallium 68 DOTANOC (DOTA-1-Nal3- octreotide) scan was done which revealed somatostatin receptor expression in enhancing soft tissue lesion in terminal ileum as well as in bilateral adnexa. This confirmed the diagnosis of NET of the ileum and bilateral ovarian metastases. The patient underwent laparoscopic curative resection of the primary tumour along with bilateral oophorectomy. The patient was diagnosed with ileal NET and presented with clinical symptoms of carcinoid syndrome, yet did not have evidence of hepatic metastasis, but instead had bilateral ovarian metastasis which itself is a rare entity.

Yaşlılarda Sağlık Hizmeti İlişkili Enfeksiyonlar: Huzurevlerine Genel Bir Bakış

Healthcare-Associated Infections in the Elderly: An Overview of Nursing Homes Although aging is a natural part of life, the risk of encountering infectious diseases increases with age due to immune senescence and the severity of infections becomes more severe. In addition, infections are sometimes difficult to diagnose because they are atypical and associated with high cost/morbidity/mortality. Infections seen in the elderly may be community-acquired infections, or they may develop as healthcare-associated infections due to the high rate of hospitalization. Healthcare-associated infections are common in vulnerable elderly populations living in long-term care facilities such as nursing homes. Common healthcare-associated infections in nursing home residents include urinary tract infections, respiratory tract infections, skin and soft tissue infections. The risk of healthcare-associated infections is high in nursing homes due to over-prescription of antibiotics, lack of proper sterilization and hygiene management, malnutrition and weakened immunity. In addition, elderly people living in institutions and with multiple hospital admissions are at risk of healthcare-associated infections caused by multidrug-resistant microorganisms, and treatment and management of these infections are difficult. Interventions and guidelines are needed to address the risks affecting the incidence of healthcare-associated infections in nursing homes in Turkey. Keywords: Healthcare-associated infection, long-term care facility, nursing home, elderly

947. Evaluating the Outcomes of Infectious Diseases Consultation on methicillin susceptible Staphylococcus aureus Bacteremia

Abstract Background In 2014, an institutional project was completed assessing outcomes of beta-lactams versus vancomycin in patients with MSSA bacteremia. This research led to the development and implementation of a new standard of care for Staphylococcus aureus bacteremia using a bundle set that included ID consultation. The purpose of this research is to evaluate the impact mandatory ID consultation had on patient outcomes since this bundle set was implemented at our institution. Methods This was a quasi-experimental, single center study of adults with MSSA bacteremia admitted from April 1, 2018 to August 31, 2021. In the instance of patients with multiple admissions with MSSA bacteremia, data from only the first admission was included in the final analysis. Patients were excluded if they had polymicrobial bacteremia or expired within 48 hours of admission. Patients were identified by utilizing reports generated from the pharmacy clinical decision support software of patients with at least one blood culture positive for MSSA. Patients in this list were further screened through manual chart review for inclusion and exclusion criteria. The primary endpoint of this study is inpatient mortality in the setting of MSSA bacteremia with and without an ID consultation. Inpatient mortality was defined as death by any cause during hospital admission. Secondary endpoints included time to bacterial clearance, ID consultation, and mortality. Results Of the patients included, only 42 percent of patients in the pre-bundle set group were treated with MSSA targeted therapy (beta-lactam), in comparison to 86 percent in the post-bundle set group. The difference in secondary outcomes was not statistically significant. For the primary outcome of inpatient all-cause mortality, a 10 percent difference was found between the pre and post-bundle set groups, 18% vs. 8% (p = 0.01). The multivariate regression analysis also confirmed that the presence of an ID consult had a significant relationship with decreased mortality (p = 0.01). Conclusion The all-cause mortality rate of adult patients with MSSA bacteremia significantly decreased after implementation of the Staphylococcus aureus bacteremia bundle set requiring an ID consultation. Disclosures All Authors: No reported disclosures.

1024. Transitions of Care Quality Metrics in Patients Discharged on Parenteral Antimicrobial Therapy in a Large Urban Hospital that Lacks a Formal Outpatient Parenteral Antimicrobial Therapy Program

Abstract Background With the evidence demonstrating the need for antimicrobial stewardship in the transition from inpatient to outpatient intravenous (IV) antibiotic therapy, it is imperative to have effective communication and coordination in a multidisciplinary team. Studies have demonstrated the utility of initiating a formal Outpatient Parenteral Antimicrobial Therapy (OPAT) program. The goal of this study is to assess quality metrics in a sample of patients discharged on IV antibiotics prior to initiation of a pilot OPAT program. Methods This is a retrospective, multicenter chart review of patients admitted to Temple University Health System from 10/1/2020 - 10/31/2021 who were discharged on IV antibiotics. There were no exclusion criteria. Patients with multiple admissions were documented as separate occurrences. Qualitative data were collected on the appropriateness of OPAT indication, pathogens targeted, antibiotics used, performance of infectious diseases (ID) consult, line selected, outcomes, and demographics. The primary endpoint is the percentage of global IV antibiotic prescribing errors (antibiotic, dose, route, frequency, duration, parenteral access device). Results There were 748 total discharges on IV antimicrobials in 705 unique patients. We chose a random sample of 109 discharges. Twenty (18%) had an oral antimicrobial available as an option. Antibiotic selection, dosing, duration, and access were correct 92%, 82%, 64% and 65% respectively (Table 2). ID recommended laboratory monitoring for 44 (40%) patients, of which 8 (18%) were sent to ID clinic; all had abnormal findings. Of the 25 patients who required ID follow-up, 11 had a scheduled ID appointment of which 8 attended. There was no mortality within 30 days from the 8 patients, but 2 were readmitted within 30 days. Overall, 39% patients readmitted within 30 days, 6% had mortality within 30 days and 50% were known to have completed therapy. Conclusion Our study captured a 65% rate of prescribing errors in a sample of 109 patients receiving IV antibiotics at discharge. The findings demonstrate an urgent need for an OPAT program to help with antimicrobial, parenteral access selection, monitoring, and follow-up with ID. By implementing this program, we hope to improve our ID follow-up, lab monitoring, and readmission metrics. Disclosures All Authors: No reported disclosures.

Lupus Enteritis: An Unusual Manifestation of Systemic Lupus Erythematosus

ABSTRACT Though gastrointestinal symptoms are common in Systemic Lupus Erythematosus (SLE), lupus enteritis remains a rare manifestation of the disease. The clinical picture may be non-specific but should be considered in patients with abdominal pain, as this disease entity can progress to intestinal necrosis and perforation if left untreated. This is a case report of a 37-year-old female who had multiple hospital admissions for abdominal pain, was diagnosed with lupus enteritis and showed excellent response to methylprednisolone.

Therapeutic Targeting of EP300/CBP By Bromodomain Inhibition in Acute Myeloid Leukemia

CCS1477 (also known as inobrodib) is a potent and selective inhibitor of the bromodomains of EP300 and CBP, two homologous histone acetyltransferases with critical roles in cellular growth and differentiation. In pre-clinical analyses we found that CCS1477 induced dose-dependent growth inhibition of a wide range of acute myeloid leukemia (AML) cell lines and primary patient samples of diverse molecular subtypes at low nanomolar concentrations. Growth inhibition was predominantly due to cell cycle arrest and differentiation; there was only modest apoptosis. In vivo, in contrast to control mice which all developed short latency AML, all animals with experimentally initiated MLL-AF9 and MLL-AF10 driven AMLs (in a retroviral transduction and transplantation syngeneic model) treated with 30mg/kg daily PO CCS1477 survived to termination of the experiment at 220 days. In subcutaneous xenograft models, there was dose-dependent growth inhibition of MOLM16 AML cell tumours, with 20mg/kg daily for 21 days completely suppressing tumour growth and no tumour regrowth until 14 days following the end of treatment. Mechanistically, we found that 100nM CCS1477 induced rapid and selective depletion of EP300 in particular from MYB binding sites in THP1 AML cells. ChIPseq demonstrated that in steady state the strongest recruitment of EP300 to chromatin in THP1 AML cells was at sites of MYB and CEBPA transcription factor occupancy, although EP300 was also found genome-wide at sites occupied by other factors including RUNX1 and ETS. Following CCS1477 treatment there was, within six hours, selective loss of EP300 at MYB occupied sites, co-localized reduced chromatin accessibility and histone H3K27 acetylation, and stalling of RNA polymerase at subordinate genes with reduced transcription. This was associated with a dose-dependent redistribution of EP300 to alternate sites and up regulation of differentiation genes. In our ongoing phase I/IIa clinical trial investigating the safety and efficacy of CCS1477 in advanced haematological malignancies (NCT04068597), we have observed therapeutically beneficial granulocytic differentiation responses in patients with high-risk myelodysplasia or relapsed AML. For example, a patient with myelodysplasia with excess blasts 2 (MDS-EB2) evolving to AML who had received three cycles of azacitidine without response was treated with CCS1477 50mg PO (once daily, three days/week). Pre-CCS1477 treatment there was profound neutropenia and multiple admissions for sepsis. After CCS1477 treatment the neutrophil count rapidly normalized and, despite a brief admission for splenic infarction in the first week, the patient remained well for 5 months with no infective episodes. Treatment was stopped due to a rising leukocyte count. Similar responses were seen in other patients. In one of these, single cell RNA sequencing of serial blood and bone marrow samples confirmed appearance of mature myeloid cells on CCS1477 treatment and, within the blast population, up regulation of a multilineage differentiation programme and down regulation of a stem cell programme. Reflecting our findings in cell line models, there was also up regulation of genes induced by MYB knockdown and concordant up and down regulation of genes regulated by CEBPA in THP1 AML cells. Finally, we evaluated the activity of CCS1477 in xenograft models in combination with existing standard of care agents. Azacitidine and CCS1477 in particular demonstrated synergistic growth inhibitory activity in the MOLM16 model, as did venetoclax in MOLM16 and MV(4;11) models. These encouraging pre-clinical and early phase clinical findings set the stage for the clinical trial evaluation of CCS1477 in combination with azacitidine and venetoclax.

Tubo-Ovarian Abscess with Actinomyces odontolyticus: Case Report and Brief Review of Literature

Actinomyces odontolyticus is a strictly anaerobic species, a member of the Actinomyces genus and of the commensal flora, especially oral flora, which can trigger severe infections through breaches in healthy tissue or necrotic tissue that are often hard to diagnose clinically and microbiologically. Most infections with this species are pulmonary or pleural, which might hint at a connection with poor dental hygiene, but other locations have been documented. We present a case of a tubo-ovarian abscess with a difficult identification of the etiological agent in a woman with multiple admissions, no significant comorbidities, and a longstanding use of an IUD (intrauterine device). To our knowledge, no previous case of tubo-ovarian abscess with an accurate A. odontolyticus microbiological species identification has been reported so far. This case also highlights the importance of considering an anaerobic species as an etiologic agent in an infectious process concerning a previously damaged tissue and the importance of appropriate harvesting and culturing in the accurate diagnosis of such species.

Abstract 13878: A Case of Severe Tricuspid Regurgitation, Recurrent Ascites, Worsening Renal Function Leading to Hemodialysis Secondary to RV Lead Impingement, Resolved Completely With Lead Extraction

Introduction: 1. In contemporary practice, implantation of Cardiovascular Implantable Electronic Devices (CIED) is associated with low complication rate peri-procedurally. 2. However, in some patients these complications can have high morbidity and mortality; namely pneumothorax, pericardial tamponade, pacemaker syndrome, and rarely tricuspid regurgitation (TR) secondary to lead impingement. 3. TR secondary to RV lead impingement is not uncommon but infrequently lead to severe TR and worsening heart failure symptoms. 4. We present a case of severe TR secondary to RV lead impingement leading to splanchnic congestion and recurrent ascites, worsening renal failure leading to hemodialysis (HD), all of which resolved with lead extraction. Case: A 77-year-old woman with known CAD with prior PTCA, paroxysmal AF, and prior watchman implantation, evaluated in our clinic for severe TR. She had recurrent admissions for ascites needing paracentesis. Her liver function and ultrasound was normal. Her renal function worsened and HD was initiated. ECHO showed normal LVEF, severe TR with RVSP of 74mmHg, and mild RV dysfunction. Pericardial physiology was normal. The lead was noted to be impinging on the septal leaflet, and adherent. Normal pulmonary valve function. Follow up: We proceeded to perform RV lead extraction and implanted a new leadless pacemaker [MICRA-AV, Medtronic Inc]. Her follow up ECHO in 2 weeks showed mild TR and normal RV function. RVSP had dropped significantly to 34mmHg. Surprisingly, her needs for paracentesis came down and by 3 months follow up she did not need paracentesis anymore. Her renal function improved, and her HD needs stopped. Conclusions: 1. CIED implantations are associated with low complication rate (less than 5% in total) in most patient cohorts but in some patients it can be associated with significant complications increasing their morbidity and sometimes mortality. 2. Severe TR is a well-recognized complication of pacemaker implantation. It led to recurrent ascites needing paracentesis, ESRD requiring HD and multiple hospital admissions and thus increasing the morbidity. 3. It is important to recognize the uncommon complications of such commonly used intracardiac devices for electrophysiologists, cardiologists and PCPs.

Obese, non-eosinophilic asthma: frequent exacerbators in a real-world setting

Objective In the UK, asthma deaths are at their highest level this century. Increased recognition of at-risk patients is needed. This study phenotyped frequent asthma exacerbators and used machine learning to predict frequent exacerbators. Methods Patients admitted to a district general hospital with an asthma exacerbation between 1st March 2018 and 1st March 2020 were included. Patients were organized into two groups: “Infrequent Exacerbators” (1 admission in the previous 12 months) and “Frequent Exacerbators” (≥2 admissions in the previous 12 months). Patient data were retrospectively collected from hospital and primary care records. Machine learning models were used to predict frequent exacerbators. Results 200 patients admitted for asthma exacerbations were randomly selected (73% female; mean age 47.8 years). Peripheral eosinophilia was uncommon in either group (21% vs 19%). More frequent exacerbators were being treated with high-dose ICS than infrequent exacerbators (46.5% vs 23.2%; P < 0.001), and frequent exacerbators used more SABA inhalers (10.9 vs 7.40; P = 0.01) in the year preceding the current admission. BMI was raised in both groups (34.2 vs 30.9). Logistic regression was the most accurate machine learning model for predicting frequent exacerbators (AUC = 0.80). Conclusions Patients admitted for asthma are predominately female, obese and non-eosinophilic. Patients who require multiple admissions per year have poorer asthma control at baseline. Machine learning algorithms can predict frequent exacerbators using clinical data available in primary care. Instead of simply increasing the dose of corticosteroids, multidisciplinary management targeting Th2-low inflammation should be considered for these patients.

ODP260 New Type of Autoimmune Diabetes

Abstract Immune checkpoint inhibitors (ICIs) are an emerging therapy that has revolutionized the management of certain cancers. Data on long-term side effects of these drugs are now showing a risk for development of new endocrinopathies. In this case report, a patient with new Type I diabetes (DMI) is discussed. The patient is a 67 year old male with past medical history of metastatic renal cell carcinoma with multiple recurrences of disease. A brief review of the patient's oncologic history revealed multiple surgeries, including complete nephrectomy, multiple drugs, including ICIs, and radiation therapy. Over the course of his treatment, he received Nivolumab (anti-PD1 agent) for 5 cycles with HbA1c increased from 5.4% to 6.9% from pre-treatment to post-treatment, but the HbA1c improved to 5.8% one year after drug cessation. Later he was started on Pembrolizumab (anti-PD1) and has had 10 cycles of therapy to date. Random blood glucose frequently exceeded 200 after start of pembrolizumab therapy. Ipilimumab (anti CTLA-4) was started in combination with pembrolizumab six months later, but it was held after the second cycle due to development of diabetes with HbA1c of 11.1%. He was also found to have persistent, severe hyperglycemia noted during routine bloodwork. Autoimmune DM was confirmed with a positive glutamic acid decarboxylase antibody (GAD65) of 8 nmol/L. Consequently, the patient had multiple hospital admissions for glucose exceeding 400. His condition was exacerbated by the fact that he had difficulty coming to terms with his diagnosis, and he was noncompliant with medication. At that time, the patient stated that he had not done anything wrong and did not understand why this had happened to him. He was resistant to starting therapy and had difficulty understanding insulin dosing, blood glucose monitoring, and the consequences of hyperglycemia/hypoglycemia. After extensive education during a 2 week hospitalization, the patient was eventually place on an appropriate dose of basal-bolus insulin therapy and is currently doing well. It is important to note some emerging challenges to treating this new population of patients with DM1 due to ICI therapy. Firstly, many patients in this scenario live alone and have poor support systems. They have difficulty learning new technology (glucometer, insulin pen, etc.) and self adjusting medication (sliding scale). Older patients can also be more resistance to change in diet and lifestyle. They may have pre-existing insulin resistance that makes initial insulin dosage difficult. Finally, noncompliance is dangerous due to risk of hypoglycemia, diabetic ketoacidosis, and exacerbation of other comorbidities. Clinicians should also consider the patient's psychosocial ability to understand and manage this condition. Presentation: No date and time listed