Acute Onset Of Disease Research Articles

Prediction of shear stress imposed on alveolar epithelium of healthy and diseased lungs.

Lung alveoli are modeled as spherical caps, lined internally by a thin surfactant-laden liquid film, and the periodic wall shear stress exerted along the epithelium during small-amplitude radial oscillations of their wall is computed. A novel set of boundary conditions, applied at the rim, reveals the dominant role of Marangoni stresses. These stresses develop along the air/liquid interface due to spatial gradients of interfacial surfactant concentration and are transported to the wall by the action of viscosity. The effect of a variety of geometric and functional characteristics, including rim interstitial thickness, alveolar opening angle and liquid film thickness and viscosity, is interrogated, and the results are discussed in relation to the onset and evolution of acute and chronic lung diseases, such as asthmatic attacks, pulmonary emphysema and pulmonary fibrosis.

New Onset of Acute and Chronic Hepatic Diseases Post-COVID-19 Infection: A Systematic Review.

The SARS-CoV-2 virus caused a pandemic in the 2020s, which affected almost every aspect of life. As the world is recovering from the effect of the coronavirus, the concept of post-COVID-19 syndrome has emerged. Multiple organ systems have been implicated, including the liver. We aim to identify and analyze the reported cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Several databases were used to conduct a comprehensive literature search to target studies reporting cases of severe and long-term parenchymal liver injury post-COVID-19 infection. Screening, data extraction, and cross checking were performed by two independent reviewers. Only 22 studies met our inclusion criteria. Our results revealed that liver steatosis, non-alcoholic fatty liver disease (NAFLD), and cirrhosis were the most reported liver associated complications post-COVID-19 infection. Moreover, complications like acute liver failure, hepatitis, and liver hemorrhage were also reported. The mechanism of liver injury post-COVID-19 infection is not fully understood. The leading proposed mechanisms include the involvement of the angiotensin-converting enzyme-2 (ACE-2) receptor expressed in the liver and the overall inflammatory state caused by COVID-19 infection. Future studies should incorporate longer follow-up periods, spanning several years, for better insight into the progression and management of such diseases.

Acute leptospirosis in horses: A retrospective study of 11 cases (2015-2023).

Reports of leptospirosis in horses are limited. To describe the clinical and diagnostic findings of acute systemic leptospirosis in horses. Eleven client-owned horses presented to an equine hospital because of acute onset of disease between 2015 and 2023. Retrospective case series. Horses diagnosed with leptospirosis by 1 or more of urine PCR, serologic microscopic agglutination test (MAT), and histopathology. Common clinical signs included lethargy (10), anorexia (10), fever (9), tachypnea (9), abnormal lung sounds (9), and epistaxis (6). Acute kidney injury was present in all cases. Evidence of pulmonary hemorrhage and liver disease was found in 8 (73%) and 6 (55%) horses, respectively. In 6 (55%) horses, kidneys, lungs, and liver were affected. Urine quantitative polymerase chain reaction for detection of pathogenic Leptospira spp. was positive in 6 (55%) cases. On serology Leptospira interrogans serovar Australis, Autumnalis, and Bratislava accounted for 86% of all titers ≥1 : 800. Overall case fatality rate was 4/11 (36%). Main findings on necropsy were tubular necrosis, interstitial nephritis, hemorrhage in the alveoli, pulmonary edema, periportal hepatitis and necrosis, cholestasis, and cholangitis. Leptospirosis should be considered as a differential diagnosis in horses with evidence of acute systemic inflammation and acute renal injury, epistaxis, or hepatic disease. For increased likelihood of identifying positive cases, both MAT serology and urine PCR should be performed.

Diagnostic value of uric acid to high-density lipoprotein cholesterol ratio in abdominal aortic aneurysms

Background Abdominal aortic aneurysm (AAA) is highly lethal upon onset of acute aortic diseases (AAD) or rupture. Dyslipidaemia and hyperuricaemia are important risk factors for the development of AAA and AAD as well as aortic disease-related death. The aim of this study was to explore whether uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) can be used as an independent predictor of the presence of AAA or AAD. Methods Three hundred subjects, including 100 AAA patients (AAA group), 100 AAD patients (AAD group) and 100 controls (CON group), were recruited in this study. UHR and other serum samples were obtained upon the patients’ admission before any medical treatment. The optimal cut-off points of UHR were determined using receiver operating characteristic (ROC) curve analysis. Results The UHR in AAA group was significantly higher than that in CON group, but there was no significant difference between AAD group and CON group. The optimal cut-off point of UHR for AAA was 7.78 (sensitivity 84.7%, specificity 62.4%, and AUC 0.811; p < 0.001), and UHR (OR: 1.122, 95%CI: 1.064-1.184; p < 0.001) was found to be an independent factor for predicting AAA after adjusting for traditional AAA risk factor. Conclusion UHR can be widely used in clinical practice as an auxiliary tool for screening AAA. The optimal cut-off point for UHR to AAA was determined for the first time in Chinese subjects.

Resilience provides mediating effect of resilience between fear of progression and sleep quality in patients with hematological malignancies.

Hematological tumors are common malignant tumors, with high morbidity and mortality rates. Most patients with hematological malignancies develop sleep disorders that seriously affect their life and health because of acute onset of disease, rapid progression, high recurrence rates, complex treatment methods, and treatment costs. To explore the mediating effect of resilience on fear of disease progression and sleep quality in patients with hematological malignancies. A cross-sectional analysis of 100 patients with hematological malignancies, treated in the First Affiliated Hospital of Jinzhou Medical University between August 2022 and August 2023, was conducted. Patients were assessed using a general data survey, a simplified scale for the fear of progression (FoP) of disease, a resilience scale, and the Pittsburgh Sleep Quality Index. Statistical analysis was conducted to determine the relationship between various patient characteristics and FoP, resilience, and sleep quality. Spearman's correlation analysis was used to examine the correlations between mental resilience, FoP, and sleep quality. The total FoP score mean value in patients with hematological malignancies was 38.09 ± 5.16; the total resilience score mean value was 40.73 ± 7.04; and the Pittsburgh Sleep Quality Index score mean value was 10.72 ± 1.90. FoP, resilience, and sleep quality of the patients were associated with family per capita monthly income and patient education level (P < 0.05). Spearman correlation analysis revealed that FoP was negatively correlated with resilience and sleep quality scores (r = -0.560, -0.537, P < 0.01), respectively, and resilience was significantly associated with sleep quality scores (r = 0.688, P < 0.01). Mediation analysis showed that the mediating effect of resilience between FoP and sleep quality in patients with hematological malignancies was -0.100 and accounted for 50.51% of the total effect. This indicated that FoP directly and indirectly affected sleep quality through the mesomeric effect of resilience. Resilience is an intermediary variable between FoP and sleep quality in patients with hematological malignancies. Medical staff should evaluate and follow-up FoP and resilience to implement measures to improve sleep quality.

Utilizing Wearable Device Data for Syndromic Surveillance: A Fever Detection Approach.

Commercially available wearable devices (wearables) show promise for continuous physiological monitoring. Previous works have demonstrated that wearables can be used to detect the onset of acute infectious diseases, particularly those characterized by fever. We aimed to evaluate whether these devices could be used for the more general task of syndromic surveillance. We obtained wearable device data (Oura Ring) from 63,153 participants. We constructed a dataset using participants' wearable device data and participants' responses to daily online questionnaires. We included days from the participants if they (1) completed the questionnaire, (2) reported not experiencing fever and reported a self-collected body temperature below 38 °C (negative class), or reported experiencing fever and reported a self-collected body temperature at or above 38 °C (positive class), and (3) wore the wearable device the nights before and after that day. We used wearable device data (i.e., skin temperature, heart rate, and sleep) from the nights before and after participants' fever day to train a tree-based classifier to detect self-reported fevers. We evaluated the performance of our model using a five-fold cross-validation scheme. Sixteen thousand, seven hundred, and ninety-four participants provided at least one valid ground truth day; there were a total of 724 fever days (positive class examples) from 463 participants and 342,430 non-fever days (negative class examples) from 16,687 participants. Our model exhibited an area under the receiver operating characteristic curve (AUROC) of 0.85 and an average precision (AP) of 0.25. At a sensitivity of 0.50, our calibrated model had a false positive rate of 0.8%. Our results suggest that it might be possible to leverage data from these devices at a public health level for live fever surveillance. Implementing these models could increase our ability to detect disease prevalence and spread in real-time during infectious disease outbreaks.

Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome.

A group of SARS-CoV-2 infected individuals present lingering symptoms, defined as long COVID (LC), that may last months or years post the onset of acute disease. A portion of LC patients have symptoms similar to myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), which results in a substantial reduction in their quality of life. A better understanding of the pathophysiology of LC, in particular, ME/CFS is urgently needed. We identified and studied metabolites and soluble biomarkers in plasma from LC individuals mainly exhibiting ME/CFS compared to age-sex-matched recovered individuals (R) without LC, acute COVID-19 patients (A), and to SARS-CoV-2 unexposed healthy individuals (HC). Through these analyses, we identified alterations in several metabolomic pathways in LC vs other groups. Plasma metabolomics analysis showed that LC differed from the R and HC groups. Of note, the R group also exhibited a different metabolomic profile than HC. Moreover, we observed a significant elevation in the plasma pro-inflammatory biomarkers (e.g. IL-1α, IL-6, TNF-α, Flt-1, and sCD14) but the reduction in ATP in LC patients. Our results demonstrate that LC patients exhibit persistent metabolomic abnormalities 12 months after the acute COVID-19 disease. Of note, such metabolomic alterations can be observed in the R group 12 months after the acute disease. Hence, the metabolomic recovery period for infected individuals with SARS-CoV-2 might be long-lasting. In particular, we found a significant reduction in sarcosine and serine concentrations in LC patients, which was inversely correlated with depression, anxiety, and cognitive dysfunction scores. Our study findings provide a comprehensive metabolomic knowledge base and other soluble biomarkers for a better understanding of the pathophysiology of LC and suggests sarcosine and serine supplementations might have potential therapeutic implications in LC patients. Finally, our study reveals that LC disproportionally affects females more than males, as evidenced by nearly 70% of our LC patients being female.

Diagnosing an Acute Leukemia From a Necrotizing Ulcerative Gingivitis in The Oral Cavity: a Case Report

Background: Necrotizing ulcerative gingivitis (NUG) is an acute onset of gingival disease, that presents as an acute, painful, and destructive ulceration and inflammation of gingival tissue. This condition is one of the oral manifestations of leukemia in addition to gingival enlargement and spontaneous bleeding, oral ulceration, petechiae, hematoma, and pale mucosa. Case Report: We reported A 50-year-old woman presented with gum swelling, pain, and easy bleeding in the lower jaw gums. The patient often experiences fatigue, spontaneous bruising, dry skin, and hair loss. Extraoral examination revealed bruises on the hand. Intraoral examination revealed swelling, erythematous and ulcerative lesion, tartar, bleeding on probing in the lingual gingiva of lower central incisor teeth, mucosa pallor, and minor petechiae were observed at the buccal mucosa region 47-48. The provisional diagnosis was NUG with suspicion of systemic disorder. Result: A complete blood count was performed which showed anemia, leukopenia, neutropenia, lymphocytosis, and thrombocytopenia. We diagnosed NUG in acute leukemia patients. Conclusion: This case demonstrates the detection of leukemia and its oral manifestations in acute leukemia patient. The patient was referred to the hematologist oncology.

The split apparent diffusion coefficient sign: A novel magnetic resonance imaging biomarker for cortical pathology with possible implications in autoimmune encephalitis.

MRI is the imaging modality of choice for assessing patients with encephalopathy. In this context, we discuss a novel biomarker, the "split ADC sign," where the cerebral cortex demonstrates restricted diffusion (high DWI signal and low ADC) and the underlying white matter demonstrates facilitated diffusion (high or low DWI signal and high ADC). We hypothesize that this sign can be used as a biomarker to suggest either acute encephalitis onset or to raise the possibility of an autoimmune etiology. A full-text radiological information system search of radiological reports was performed for all entities known to produce restricted diffusion in the cortex excluding stroke between January 2012 and June 2022. Initial MRI studies performed upon onset of clinical symptoms were screened for the split ADC sign. 25 subjects were encountered with a positive split ADC sign (15 female; median age = 57years, range 18-82). Diagnosis included six herpes simplex encephalitis, three peri-ictal MRI changes, eight PRES, two MELAS, and six autoimmune (3 anti-GABAAR, two seronegative, and one anti-Ma2/Ta). Subjects were imaged at a mean 1.8days after the onset of symptoms (range 0-8). We present a novel visual MRI biomarker, the split ADC sign, and highlight its potential usefulness in subjects with encephalopathy to suggest acute disease onset or to raise the possibility of an autoimmune etiology when location-based criteria are applied. When positive, the sign was present on the initial MRI and can therefore be used to help focus further clinical and laboratory workup.

First Swedish case of fatal equine parasitic encephalitis by Halicephalobus gingivalis

BackgroundHalicephalobus gingivalis is a nematode with zoonotic potential which can cause fatal opportunistic infections in various mammals. The parasite has never been diagnosed in Sweden, in any species, prior to the presented case.Case presentationAn imported 21-year-old Icelandic mare developed severe neurological signs. The horse was eventually euthanized and submitted for post-mortem examination where severe lesions in the kidneys were noted. Histopathology revealed the presence of H. gingivalis in both kidneys and the brain. Phylogenetic analysis of the parasite determined it to belong to Lineage 1.ConclusionsWith the occurrence of H. gingivalis in Sweden, the disease should be added to the list of differential diagnoses in cases with acute onset of neurological disease in both horses and other mammals including humans.

Acute Onset of Creutzfeldt-Jakob Disease Resembling Stroke in Absence of Diagnostic EEG Findings

We report a case of Creutzfeldt-Jakob disease with acute onset of symptoms with EEG negative for PSWC, resembling a cerebrovascular accident. The patient was diagnosed with sporadic CJD by positive RT-QUIC, positive 14-3-3 protein, T-Tau protein of 14560 pg/mL, brain magnetic resonance imaging (MRI) demonstrating restricted diffusion on DWI in bilateral frontal, temporal, occipital cortex, caudate and putaminal nuclei, as well as T2 FLAIR hyperintensities in the bilateral cerebral cortex and basal ganglia. The entire course of the disease from onset to death was 52 days.

Development of nanoparticle‐based drug delivery system for inflammation treatment and diagnosis

AbstractInflammation is a prevalent pathological process that accompanies the onset and progression of numerous acute and chronic diseases including rheumatoid arthritis, sepsis, pancreatitis, atherosclerosis, ischaemic brain/heart disease and so forth. However, conventional anti‐inflammatory drugs have certain disadvantages such as nonspecific tissue distribution, low bioavailability, and a short half‐life, resulting in off‐target side effects and limited efficacy in disease control. To address these issues, nanoparticles have emerged as a novel therapeutic paradigm in this field to attain inflammation targeting and improve drug pharmacokinetic properties via the well‐recognized enhanced permeability and retention (EPR) effect at the inflammatory site. Existing reviews are predominantly centered on inflammatory pathology introduction and vector design. As a necessary complement, this review mainly elaborates on the introduction of inflammation core events, the history of the drug delivery system for anti‐inflammatory drugs, the action mechanism of inflammation targeting vectors, nanoparticle classification based on targeting moiety, methods to combine targeting moiety with core nanoparticles, techniques to assess targetability in vitro and in vivo and finally the challenges and prospects in this field. The information provided herein offers practical guidance to researchers seeking to develop and evaluate inflammation targeting vectors rationally.

Study of Blood Analysis of First-year Indian Students Upon Arrival in Kyrgyzstan (Bishkek)

Our study focuses on the analysis of red blood cells and leukocyte formula indicators in foreign students from India upon their arrival in Kyrgyzstan. Based on the leukocyte formula results, during the short-term adaptation phase, no tendencies of overexertion or disruptions in the adaptation mechanism were observed among both male and female Indian students. Furthermore, there was no observed decline in health levels or the onset of acute and chronic diseases during this period. The resilience of the body to stress reactions under different socio-climatic conditions showed that the general blood analysis parameters for these students remained within the bounds of stable homeostasis, determined by their individual potential.

Cancer and idiopathic inflammatory myopathies –association of autoantibodies with carcinogenesis

The relationship between cancer development in the course of idiopathic inflammatorymyopathies (IIM) has already been noticed at the beginning of the 20th century. However, theunderlying mechanisms remain not fully understood. Risk factors for carcinogenesis in patientswith IIM include male sex, older age, and the presence of specific subtypes of inflammatorymyopathies and clinical manifestations, including dermatomyositis, dysphagia, severe skinchanges, leukocytoclastic vasculitis, acute disease onset and immunosuppressive therapyresistance. The presence of certain autoantibodies in the serum of patients with IIM is a factorof considerable importance in the stratification of cancer risk. Anti-TIF1γ autoantibodies, which might be present in even 38-80% of cancer cases in adult IIM patients, are antibodies with a wellstudiedrelationship with carcinogenesis. The relationship of other antibodies found in IIM withthe risk of carcinogenesis is still discussed. This group includes anti-NXP2, anti-HMGCR, anti-SAE1 and anti-Mi2 antibodies. Due to the contrary reports on the role of these antibodies incancer development and their relatively low prevalence in IIM, the unambiguous classificationas risk factors requires further research in larger study groups. The potential autoantibodiesutility in cancer screening in IIM patients could help detect cancer early, improving prognosisand long-term survival.

The atherosclerotic cardiovascular disease risk score is a reliable tool to identify patients with arteriogenic erectile dysfunction.

The atherosclerotic cardiovascular disease risk score is a validated algorithm predicting an individual's 10-year risk of developing acute cardiovascular events (cardiovascular disease). Patients who suffer from arteriogenic erectile dysfunction are susceptible to developing cardiovascular disease in the future. To apply the atherosclerotic cardiovascular disease score at a homogenous cohort of men with erectile dysfunction undergoing a dynamic penile colour Doppler duplex ultrasound and explore its predictive ability to identify patients with vasculogenic erectile dysfunction at colour Doppler duplex ultrasound. Complete data of 219 patients undergoing colour Doppler duplex ultrasound were analysed. All patients completed the International Index of Erectile Function. The atherosclerotic cardiovascular disease score and Charlson comorbidity index were applied to the entire cohort. Patients were divided into those with normal vs. pathological parameters at colour Doppler duplex ultrasound. Descriptive statistics were used to explore differences between the two groups. Logistic regression models tested the potential role of atherosclerotic cardiovascular disease to predict arteriogenic and/or venogenic erectile dysfunction. Local polynomial smoothing models graphically displayed the probability of pathological colour Doppler duplex ultrasound parameters at different atherosclerotic cardiovascular disease scores. Overall, arteriogenic erectile dysfunction and venous leakage were diagnosed in 88 (40.2%) and 28 (12.8%) patients respectively. The median (interquartile range) atherosclerotic cardiovascular disease score was 7.7 (3.9-14). Patients with pathologic colour Doppler duplex ultrasound were older (59vs. 54 years, p<0.001), had higher Body Mass Index (26.5vs. 25.6kg/m2 , p=0.04), more comorbidities (Charlson comorbidity index ≥ 1) (76.5%vs. 54.4%, p=0.002) and higher median atherosclerotic cardiovascular disease scores (9.95vs. 7, p=0.005), respectively. At logistic regression analysis, a higher atherosclerotic cardiovascular disease risk score was independently associated with arteriogenic erectile dysfunction at colour Doppler duplex ultrasound (odds ratio: 1.03, 95% confidence interval: 1.01-1.08, p=0.02) after adjusting for Body Mass Index, physical activity, alcohol consumption and severe erectile dysfunction. As vasculogenic erectile dysfunction may precede bysome years the onset of acute cardiovascular diseases, the rigorous identification of patients with deficient cavernosal arterial blood flow, would definitely allow the implementation ofearlier and more effective cardiovascular prevention strategies in men with erectile dysfunction. The atherosclerotic cardiovascular disease risk score represents a reliable tool to identify patients with arteriogenic erectile dysfunction in everyday clinical practice.

Circadian variation in stroke onset: Differences between ischemic and hemorrhagic stroke and weekdays versus weekends

ObjectivesTo delineate diurnal variation onset distinguishing ischemic from hemorrhagic stroke, wake from sleep onset, and weekdays from weekends/holidays. Materials and MethodsWe analyzed patients enrolled in the FAST-MAG trial of field-initiated neuroprotective agent in patients with hyperacute stroke within 2h of symptoms onset. Stroke onset times were analyzed in 1h, 4h, and 12h time blocks throughout the 24h day-night cycle. Patient demographic, clinical features, stroke severity, and prehospital workflow were evaluated for association with onset times. ResultsAmong 1615 acute cerebrovascular disease patients, final diagnoses were acute cerebral ischemia in 76.5% and Intracerebral hemorrhage in 23.5%. Considering all acute cerebrovascular disease patients, frequency of wake onset times showed a bimodal pattern, with peaks on onsets at 09:00-13:59 and 17:00-18:59 and early morning (00:00-05:59) onset in only 3.8%. Circadian rhythmicity differed among stroke subtypes: in acute cerebral ischemia, a single broad plateau of elevated incidences was seen from 10:00-21:59; in Intracerebral hemorrhage, bimodal peaks occurred at 09:00 and 19:00. The ratio of Intracerebral hemorrhage to acute cerebral ischemia occurrence was highest in early morning, 02:00-06:59. Marked weekday vs weekends pattern variation was noted for acute cerebral ischemia, with a broad plateau between 09:00 and 21:59 on weekdays but a unimodal peak at 14:00-15:59 on weekends. ConclusionsWake onset of acute cerebrovascular disease showed a marked circadian variation, with distinctive patterns of a broad elevated plateau among acute cerebral ischemia patients; a bimodal peak among intracerebral hemorrhage patients; and a weekend change in acute cerebral ischemia pattern to a unimodal peak.

Inflammatory myositis-associated interstitial lung disease can be distinguished from that associated with other connective tissue diseases.

Acute onset of interstitial lung disease (ILD) has been described in patients with idiopathic inflammatory myositis (IIM), but controlled studies about this issue are sparse. The aim of this study was to compare disease onset, demographics, and high-resolution computed tomography (HRCT) patterns in IIM-ILD and other connective tissue disease (CTD)-ILDs. Clinical and radiological data of 22 IIM-ILD and 132 other CTD-ILD patients was retrospectively gathered from hospital registries between January 2000 and November 2019. Data was re-assessed and compared using a multivariate analysis. Compared to other CTD-ILDs, the patients with IIM-ILD were younger (59.7 vs. 68.0 years, P=0.023), more often non-smokers (71.4% vs. 45.7%, P=0.029) and displayed radiological nonspecific interstitial pneumonia/organizing pneumonia (NSIP/OP) overlap pattern more frequently (27.3% vs. 1.5%, P<0.001). The onset of ILD was acute with patients needing intensive care significantly more often in IIM-ILD than in other CTD-ILDs (22.7% vs. 2.3%, P<0.001). In most patients ILD was diagnosed before or simultaneously with IIM presentation unlike in other CTD-ILDs (90.9% vs. 47.7%, P<0.001). In multivariate analysis, NSIP/OP overlap pattern, acute onset disease treated in intensive care unit and ILD preceding or being diagnosed simultaneously with CTD were significantly associated with IIM-ILD. The multivariate model, supplemented with age, had excellent diagnostic performance identifying IIM-ILD [area under curve (AUC) 0.845]. Unlike other CTD-ILDs, IIM-ILD often develops acutely, simultaneously with the systemic disease. Therefore, clinicians should consider IIM-ILD as an option of differential diagnosis in patients with acute ILD and promptly test muscle enzymes as well as comprehensive autoantibody tests.

Quality of Life (QoL) in Non-Acute Vogt–Koyanagi–Harada Disease (VKHD) at Two Time Points 24 Months Apart

ABSTRACT Aims To investigate the changes in quality-of-life (QoL) metrics at a 24-month interval in non-acute VKHD patients and their association with inflammation, treatment, and visual function. Methods SF-36 and VFQ-25 questionnaires were administered at two 24-month-apart moments to 22 non-acute VKHD patients followed for ≥12 months since acute disease onset. “Improvement,” “unchanged,” or “worsening” in questionnaires scores (difference >5-point) between M1 and M2 and their associations were sought. Results Absence of systemic treatment or optic disc hyperfluorescence was associated with improved general health (SF-36). Improvement in binocular contrast sensitivity resulted in better ocular pain score; absence of anterior uveitis relapse, stable fundus findings, no use of cyclosporine or no intravitreal injections resulted in unchanged/better dependency score; no intravitreal injections resulted in unchanged/better mental health score (VFQ-25). Conclusion Stability/improvement in QoL scores was associated with controlled inflammation, better visual function, and no need for treatment. Subclinical inflammatory signs did not impact QoL scores.

The incidence and impact of clostridioides difficile infection on transplant outcomes in acute leukemia and MDS after allogeneic hematopoietic cell transplant-a CIBMTR study.

Clostridioides difficile infection (CDI) is common after allogeneic hematopoietic cell transplantation (alloHCT). The determination of incidence, risk factors, and impact of CDI on alloHCT outcomes is an unmet need. The study examines all patients aged 2 years and older who received first alloHCT for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or myelodysplastic syndrome (MDS) between 2013 and 2018 at US centers and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) data registry. In total, 826 patients with CDI and 6723 controls from 127 centers were analyzed. The cumulative incidence of CDI by day 100 was 18.7% (99% CI: 15-22.7%) and 10.2% (99% CI: 9.2-11.1%) in pediatric and adult patients, respectively, with a median time to diagnosis at day +13. CDI was associated with inferior overall survival (OS) (p = 0.0018) and a 2.58-fold [99% CI: 1.43-4.66; p < 0.001] increase in infection-related mortality (IRM). There was a significant overlap in the onset of acute graft versus host disease (aGVHD) and CDI. IRM increased to >4 fold when CDI + aGVHD was considered. Despite advances in the management of CDI, increased IRM and decreased OS still results from CDI.

The Easix Score Predicts Overall Survival and Late Relapse in Patients Undergoing Reduced Intensity Conditioned Allogeneic Stem Cell Transplantation for Myeloid Disease

Background Allogeneic hematopoietic stem cell transplantation (alloSCT) is an effective treatment for myeloid malignancies, however outcomes post-transplant are variable and predictive scores limited. The Endothelial Activation and Stress Index (EASIX) measured at key timepoints pre- and post-transplant has been shown to predict outcomes in alloSCT, including overall survival, non-relapse mortality and incidence of sinusoidal obstructive syndrome (SOS). It can be readily calculated using standard biomarkers (LDH (U/L) x creatinine (mg/dL)/platelets (x109/L). We sought to examine its predictive role in a homogenous population of patients. Methods We conducted a retrospective national review of 117 patients undergoing reduced-intensity alloSCT for myeloid disease including AML (n=56), MDS (n=35) and MPN (n=26). All included received fludarabine, busulfan and rabbit anti-thymocyte globulin (Flu/Bu/ATG) conditioning from 2015-2020. We calculated the EASIX score on the day prior to conditioning, on day 0, at onset of acute graft versus host disease and 1 year post transplant. Univariate analysis was conducted in the STATA statistical package. Results At the pre-conditioning time-point the mean EASIX was 3.11 (0.3-17.54). Increased scores correlated with and were reliably predictive of reduced overall survival (p=0.034) (fig. 1). Higher scores at this time-point did not predict chronic GVHD or relapse, however an increased rate of acute GVHD was seen in those with lower EASIX (p=0.012). At day 0 the mean EASIX was 15.38 (1.07-179.02), however we could not demonstrate a predictive effect on SOS as no events occurred in this cohort. Nor did we identify a predictive value at this point for GVHD risk or relapse. At onset of acute GVHD (n=67, mean 3.52, 0.44-51.43), the EASIX score was predictive of overall survival (p=0.027) but did not predict risk of chronic GVHD or relapse. At 1 year post-transplant (n=88, mean 2.09, 0.48-13.59) a higher score showed a trend towards decreased overall survival (p=0.1) but was associated with an increased risk of subsequent relapse (p=0.01)(fig. 2). Conclusions The EASIX score is an easily applicable clinical tool using real world biomarkers readily available at serial time-points in transplant recipients. When applied to our homogenously treated cohort it retains its value in predicting overall mortality at the key time points of pre-conditioning and at onset of GVHD. Adoption of this simple score may be of benefit in risk stratifying the transplant process for reduced intensity conditioned allograft recipients, particularly when combined with established prediction tools for non-relapse mortality such as the HCT-CI. In addition to this, we have shown that the EASIX score may be a useful predictive tool for late relapse in those patients who are alive at 1 year post transplant. We suspect that this effect is primarily reflective of those patients with persistent thrombocytopenia and raised LDH, both markers of potential disease activity. Importantly, the use of this score in the reduced intensity population may be particularly relevant due to the increasing age of transplant eligibility and its use as a surrogate of endothelial dysregulation and potential for end organ complications through the transplant process. To assess the underlying T cell mediated and cytokine secretome effects on endothelial dysfunction, an observational study is ongoing at our institution, examining the interplay of immunomodulatory therapy, graft T cell content, early T and NK cell recovery and the cytokine secretion patterns at various time points before, during and after transplant in reduced intensity conditioned patients with myeloid disease. We plan to correlate these data with serial EASIX assessments to identify the determinants of the underlying biological process and identify potential time-points and biological targets for future study.