Neuroimmunological investigations of cerebrospinal fluid in patients with recent onset depression – a study protocol

Background A proinflammatory response has been suggested to be involved in the pathophysiology of depression in a subgroup of patients. However, comprehensive largescale studies on neuroimmunological investigations of the cerebrospinal fluid (CSF) are lacking and no largescale longitudinal CSF studies comparing patients with depression to healthy controls currently exist. Methods A longitudinal case-control study including at least 100 patients with first time depression (ICD-10: F32) within the past year with ongoing symptoms and at least 100 sex and age matched healthy controls with collection of CSF, blood, and fecal samples. All individuals will be evaluated by neurological examination including neurological soft signs, interviewed for psychopathology assessment and have symptomatology evaluated by relevant rating scales. Level of functioning and quality of life will be evaluated by a panel of interview questions and rating scales, and cognitive function assessed by a relevant test battery. In addition, a large number of potential confounders will be registered (BMI, smoking status, current medication etc.). Primary outcomes: CSF white cell count, CSF/serum albumin ratio, CSF total protein levels, IgG index, CSF levels of IL-6 and IL-8, and the prevalence of any CNS-reactive autoantibody in CSF and/or blood. Secondary outcomes: exploratory analyses of a wide range of neuroimmunological markers and specific autoantibodies. Power calculations are computed for all primary outcomes based on previous CSF studies including patients with depression and healthy controls. Discussion This study will represent the hitherto largest investigation of CSF in patients with recent onset depression compared to healthy controls. We expect to elucidate neuroimmunological alterations in individuals with depression and characterize an immunological profile paving the way for the development of effective treatments based on biomarkers. Trial registration The study is approved by The Regional Committee on Health Research Ethics (Capital Region, j.no: H-16030985) and The Danish Data Protection Agency (j.no: RHP-2016-020, I-Suite no.: 04945).

Mid-regional proadrenomedullin (MR-proADM), C-reactive protein (CRP) and other biomarkers in the early identification of disease progression in patients with COVID-19 in the acute NHS setting

AimsThere is a lack of biomarkers validated for assessing clinical deterioration in patients with COVID-19 on presentation to secondary or tertiary care. This evaluation looked at the potential clinical application of C reactive protein (CRP), procalcitonin, mid-regional proadrenomedullin (MR-proADM) and white cell count to support prediction of clinical outcomes.Methods135 patients presenting to Hampshire Hospitals NHS Foundation Trust between April and June 2020 confirmed to have COVID-19 via reverse-transcription-qPCR were included. Biomarkers from within 24 hours of presentation were used to predict disease progression by Cox regression and area under the receiver operating characteristic curves. The endpoints assessed were 30-day all-cause mortality, intubation and ventilation, critical care admission and non-invasive ventilation (NIV) use.ResultsElevated MR-proADM was shown to have the greatest ability to predict 30-day mortality adjusting for age, cardiovascular disease, renal disease and neurological disease. A significant association was also noted between raised MR-proADM and CRP concentrations and the requirement for critical care admission and NIV.ConclusionsThe measurement of MR-proADM and CRP in patients with confirmed COVID-19 infection on admission shows significant potential to support clinicians in identifying those at increased risk of disease progression and need for higher level care, subsequently enabling prompt escalation in clinical interventions.

Epidemiological Characteristics of Hospitalized Patients with Moderate versus Severe COVID-19 Infection: A Retrospective Cohort Single Centre Study

COVID-19 has a devastating impact worldwide. Recognizing factors that cause its progression is important for the utilization of appropriate resources and improving clinical outcomes. In this study, we aimed to identify the epidemiological and clinical characteristics of patients who were hospitalized with moderate versus severe COVID-19 illness. A single-center, retrospective cohort study was conducted between 3 March and 9 September 2020. Following the CDC guidelines, a two-category variable for COVID-19 severity (moderate versus severe) based on length of stay, need for intensive care or mechanical ventilation and mortality was developed. Data including demographic, clinical characteristics, laboratory parameters, therapeutic interventions and clinical outcomes were assessed using descriptive and inferential analysis. A total of 1002 patients were included, the majority were male (n = 646, 64.5%), Omani citizen (n = 770, 76.8%) and with an average age of 54.2 years. At the bivariate level, patients classified as severe were older (Mean = 55.2, SD = 16) than the moderate patients (Mean = 51.5, SD = 15.8). Diabetes mellitus was the only significant comorbidity potential factor that was more prevalent in severe patients than moderate (n = 321, 46.6%; versus n = 178, 42.4%; p < 0.001). Under the laboratory factors; total white cell count (WBC), C-reactive protein (CRP), Lactate dehydrogenase (LDH), D-dimer and corrected calcium were significant. All selected clinical characteristics and therapeutics were significant. At the multivariate level, under demographic factors, only nationality was significant and no significant comorbidity was identified. Three clinical factors were identified, including; sepsis, Acute respiratory disease syndrome (ARDS) and requirement of non-invasive ventilation (NIV). CRP and steroids were also identified under laboratory and therapeutic factors, respectively. Overall, our study identified only five factors from a total of eighteen proposed due to their significant values (p < 0.05) from the bivariate analysis. There are noticeable differences in levels of COVID-19 severity among nationalities. All the selected clinical and therapeutic factors were significant, implying that they should be a key priority when assessing severity in hospitalized COVID-19 patients. An elevated level of CRP may be a valuable early marker in predicting the progression in non-severe patients with COVID-19. Early recognition and intervention of these factors could ease the management of hospitalized COVID-19 patients and reduce case fatalities as well medical expenditure.

P-EGS13 Risk Factors of Bleeding Gastroduodenal Ulcer Among Patient Undergo Emergency Upper Endoscopy in Hospital Melaka

Background Bleeding gastroduodenal ulcer has been one of the leading causes of admission in surgical or gastroenterology departments all over the world, requiring immediate intervention with high associated mortality exceeding 10%. We analyzed few important risk factors that lead to this potentially ill condition. Methods Data from a number of 548 patients who underwent emergency upper endoscopy were collected retrospectively from June 2020 till June 2021 in Hospital Melaka. Results From our data collection of emergency upper endoscopy performed, 111 patients had findings of high-risk ulcer (Forrest Ia, Ib, 2a and 2b). From these 111 patients, the most common presentation was low hemoglobin value (&lt;10g/dL), with 43.6%. Presentation of melena encountered the second most common symptom (26.3%), while fresh per rectal bleeding counts the less common symptom (1%). Forrest Ib ulcer showed the commonest diagnosis found during endoscopy (45.5%), followed by Forrest IIa ulcer (34.5%), Forrest IIb ulcer (16.4%), and Forrest Ia ulcer (3.6%). There were 27 participants who undergo repetitive endoscopy. For Helicobacter Pylori infection, there were 367 patients (66.7%) underwent the test during endoscopy, which showed 187 patients detected (51%) with H.Pylori positive. We identify other risk factors which lead to this fatal condition such as, patient’s comorbidities including liver disease, renal disease and their medications, blood investigations including hemoglobin level, platelet count, total white cell count, total bilirubin, Alanine Transaminase (ALT), serum urea and creatinine. Conclusions It is a must to identify important risk factors for bleeding gastroduodenal ulcers to prevent morbidity and mortality, and to initiate emergency intervention medically and surgically. From this study, it was a great move for us to make further research on how these risk factors affecting our management of patients.

P-OGC79 Post-operative NUn score as a prognostic tool for anastomotic leak after Oesophagectomy

Background Anastomotic leak (AL) after esophagectomy is still quite high with incidence reported between 5 and 20%. Early detection of AL will enable patient rescue and the remedial measures may decrease the associated significant morbidity and improve quality of life. Oesophagectomy is also associated with other infective complications such as respiratory infections and collections in the abdomen or chest. Noble and Underwood (NUn) published the NUn score combining blood-borne markers of systemic inflammatory response to define risk of anastomotic leak and major complications following oesophageal resection. This study aims to validate the ability of NUn score to identify AL specifically. Methods A total of 113 patients who underwent esophagectomy for oesophageal cancer over 11 years from 2011 to early 2021 in our centre were selected for this study from a prospectively maintained database. Patients with leaks (n = 11) were identified by reviewing their case records, electronic records, endoscopy and radiological results. Patients with missing values were excluded. Postoperative 7-day (POD) biochemical data that included white cell count (WCC), C-reactive protein (CRP) and Albumin were used to calculate NUn score. Sensitivity and Specificity of NUn score with a cut-off value of &gt; 10 was calculated using the ROC curve analysis using SPSS. Results A total of 99 patients were included, among which 10 patients had anastomotic leaks (AL). Overall mean of NUn of patients with AL was 10.25 vs 9.95 without AL. NUn scores for day 1 to 7 are shown in the table in figure 1. NUn with the highest AUC was Day 7 (0.664 [CI 0.499 – 0.829]; p = 0.09), with 70% sensitivity and 57.3% specificity. The trends in WCC, CRP and albumin levels over 7 days were also not helpful in differentiating patients with AL. Conclusions In this study, the trends in rising WCC, CRP and decreasing albumin were not helpful in diagnosing anastomotic leaks specifically. The NUn score had a sensitivity of 70% on day 7. Procalcitonin, blood urea nitrogen or interleukin levels may help, and further studies are being planned. This study shows that current biochemical parameters can complement but not replace careful and regular medical examination and early radiological or endoscopic evaluation if an AL is suspected.

P-BN49 The predictive role of white cell and platelet count for infective complications following splenectomy

Background Temporary elevation of white cell count (WCC) and platelets are commonly observed after splenectomy and can therefore make it difficult for the surgeon to distinguish a normal physiological response from potential infection. Clinicians are often misled by elevated post-operative WCC after splenectomy, resulting in delayed discharges and prolonged unnecessary hospital stays for patients. The aim of this study was to establish what constitutes a normal rise in WCC and platelets after splenectomy. Methods All 127 patients who had undergone a splenectomy between July 2016 and January 2021 were identified from a search of our centre's hospital episode statistics data. WCC and platelet count on post-operative days one to seven as well as at least one long-term follow-up result count were identified from electronic hospital records. Hospital records were searched for data on pre-operative steroid administration and peri-operative infections. These cohort data were retrospectively analysed in SPSS using stepwise logistic regression, correlation analysis, and T-tests, as well as descriptive statistics. Results 86 (68%) patients underwent an elective splenectomy and 41 (32%) an emergency splenectomy. 35 (27.6%) patients developed infections post-operatively, while 92 (72.4%) did not. Logistic regression suggested that a raised WCC (above 17.5x109/L) at day 3 post-op was a significant predictor of infection (p &lt; 0.001): average WCC at day 3 for patients with infection was 20.00x109/L (SD = 6.23x109/L) compared to 14.86x109/L (SD = 4.01x109/L) for those without. Infective outcomes were not influenced by whether the surgery was emergency or elective. Overall, average WCCs were 9.63x109/L pre-operatively and 15.07x109/L long-term post-operatively. Even in the absence of infection, splenectomy led to a long-term rise in WCC of 3.8x109/L from baseline, to an average of 13.0x109/L [SD = 5.41x109/L): a T-test on the 56 patients without infection and with both pre-op and long-term WCCs showed a mean rise of 3.76x109/L, p &lt; 0.0001). Platelet count was not correlated with infection, though platelet counts rose from a mean of 261 × 109/L (SD = 103.4x109/L) pre-operatively to 581 × 109/L (SD = 236.3x109/L) at 7-day and 619 × 109/L (SD = 293.5x109/L) at long-term follow up across all patients – an average increase of 357 × 109/L, which did not significantly differ between patients with and without infective complications. Conclusions A rise in WCC and platelet count is normal post-splenectomy. A rise in WCC&gt;17.5x109/L on day 3 post-splenectomy is strongly correlated with infection (regardless of trauma or platelet count). Long-term follow up suggests that while much of the WCC increase is transient, WCC remains higher than pre-operatively, as does platelet count, in post-splenectomy patients. A raised WCC or platelet count without signs of infection should not preclude timely discharge in otherwise well patients.

A Clinical Prognostic Index for Angioimmunoblastic T Cell Lymphoma in an Asian Multi-Centre Study

Background and aims: Angioimmunoblastic T cell Lymphoma (AITL) is a subtype of peripheral T cell lymphoma that is generally felt to be aggressive and of poor prognosis. It is characterized as a lymphoma associated with inflammatory and immune conditions, typically seen in the older population and presenting at more advanced stages. The International T-Cell Lymphoma project recently reported a novel AITL score comprising of age, ECOG performance status, serum CRP level and serum B2-microglobulin level; the latter 2 variables suggesting a pro-inflammatory state. They also found that progression of disease within 24 months (POD24) to be strongly prognostic. In our Asian multicenter study, we aim to investigate the clinical prognostic factors affecting the outcomes of our AITL patients and attempt to identify a prognostic index that would be relevant to our Asian population. Methods: Patients who were consecutively diagnosed with AITL and seen at National Cancer Centre Singapore and Singapore General Hospital between June 1999 and Dec 2019 were retrospectively analyzed. Relevant demographical and clinical characteristics were collected. Median duration of follow up was 19.7 months. Outcomes of interest were that of 5-year overall survival (OS) and 5-year progression free survival (PFS). POD24 as defined by progression of disease within 24 months was also analyzed for its prognostic significance. Kaplan meier curves were plotted to estimate survival for each individual clinical parameter. Parameters found to be significant on univariate analysis were subsequently used in generation of multivariate cox regression models. Results: A total of 166 patients were included. The median age was 62.1 years. The majority of our patients (92.8%) had good performance status of ECOG 0-1 and 77.7% presented at advanced stages (Ann Arbor stage 3-4). The median PFS and OS was 1.5 years and 5.5 years respectively. The estimated 5-year PFS and OS was 40% and 53% respectively. Univariate analyses of various parameters were significant for age &gt;60 years, presence of B symptoms, ECOG &gt;1, Ann Arbor stage 3-4, bone marrow involvement, elevated serum lactate dehydrogenase &gt; upper limit normal, elevated total white cell count &gt; 12 x 10 9/L and low platelet count &lt; 150,000/mm 3. In the multivariate analyses, age &gt;60 years, bone marrow involvement, elevated total white cell count and low platelet count were associated with poorer PFS and OS. This allowed for a prognostic index (AITL-PI) differentiating patients into low (0-1 factors, n=62), moderate (2 factors, n=54) and high (3-4 factors, n=48) risk subgroups with 5-year OS of 83%, 41% and 26% respectively. The corresponding 5-year PFS of the low, moderate and high risk subgroups are 69%, 29% and 14%. Likewise, POD24 proved to be strongly prognostic in our cohort as patients with POD24 had a 5-year OS of 24%, whereas those without POD24 had a 5-year OS of 90% (p&lt;0.0001). Conclusion: We validated POD24 as a strong prognostic factor. Our AITL-PI was able to identify 3 different subgroups of patients with disparate outcomes based on their presenting clinical parameters. Further work can be done to elucidate if there are unique pathological or molecular characteristics in these individual risk groups that can further guide treatment choices. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Catatonia: demographic, clinical and laboratory associations

Background Catatonia, a severe neuropsychiatric syndrome, has few studies of sufficient scale to clarify its epidemiology or pathophysiology. We aimed to characterise demographic associations, peripheral inflammatory markers and outcome of catatonia. Methods Electronic healthcare records were searched for validated clinical diagnoses of catatonia. In a case–control study, demographics and inflammatory markers were compared in psychiatric inpatients with and without catatonia. In a cohort study, the two groups were compared in terms of their duration of admission and mortality. Results We identified 1456 patients with catatonia (of whom 25.1% had two or more episodes) and 24 956 psychiatric inpatients without catatonia. Incidence was 10.6 episodes of catatonia per 100 000 person-years. Patients with and without catatonia were similar in sex, younger and more likely to be of Black ethnicity. Serum iron was reduced in patients with catatonia [11.6 v. 14.2 μmol/L, odds ratio (OR) 0.65 (95% confidence interval (CI) 0.45–0.95), p = 0.03] and creatine kinase was raised [2545 v. 459 IU/L, OR 1.53 (95% CI 1.29–1.81), p < 0.001], but there was no difference in C-reactive protein or white cell count. N-Methyl-d-aspartate receptor antibodies were significantly associated with catatonia, but there were small numbers of positive results. Duration of hospitalisation was greater in the catatonia group (median: 43 v. 25 days), but there was no difference in mortality after adjustment. Conclusions In the largest clinical study of catatonia, we found catatonia occurred in approximately 1 per 10 000 person-years. Evidence for a proinflammatory state was mixed. Catatonia was associated with prolonged inpatient admission but not with increased mortality.

1303. A Rare Case of Legionella micdadei Lung Abscess in an Immunocompromised Patient

Background Legionella micdadei is the most common legionella species causing infection after L. pneumophila. It usually causes infection in immunocompromised hosts and leads to nodules with tendency to cavitate. It is difficult to culture which makes diagnosis challenging. We report a case or L. micdadei in an immunocompromised host with cavitary pneumonia. Methods Case Report. An 82 year-old female presented with upper abdominal pain for one day duration. She has history of hypertension, coronary artery disease, hyperlipidemia, heart failure, and hypothyroidism. She was diagnosed with hypersensitivity pneumonia 5 months prior, treated with prednisone (40 mg daily). The pain was not associated with nausea, vomiting or diarrhea. She was found with hypoxia despite she denied shortness of breath, cough, hemoptysis or chest pain. There was no fever, chills, headache, myalgia or upper respiratory symptoms. She was afebrile, tachycardic 134/min and hypoxic to 88% on room air. White cell count was 22x10(3) /mcL (90% neutrophils), hemoglobin was 10.4 g/dL, creatinine was 1.23 mg/dL and lactic acid was 3.6 mmol/L. Chest CT scan showed left lower lobe cavitary lesion with surrounding infiltrates (image 1). Quantiferon gold, serum galagtomannan, B-D-glucan, and vasculitis work-up were negative. Bronchoscopy showed a patent airway. Bronchial smears and cultures were negative for bacteria, fungi and mycobacteria. The patient was treated with ceftriaxone and metronidazole with de-escalation to amoxicillin/clavulanate. Bronchial culture was positive for legionella micdadei after discharge, azithromycin was added. Image 1. Cavitary lesion on thoracic CT Results Our patient was considered immunocompromised given steroid use, predisposing her for L. micdadei infection. L. micdadei is considered an opportunistic infection and was reported in hematologic malignancy population. It can cause an invasive lung disease with lung cavities. It needs special media for growth making it difficult to diagnose especially it is not detected by legionella urine antigen. Conclusion L. micdadei should be considered in the differential diagnosis for cavitary lung lesions in immunocompromised patients. Disclosures All Authors: No reported disclosures