Affected Organ Systems Research Articles

A rare case of high risk multisystem Langerhans Cell Histiocytosis in infant

Objective: Langerhans cell histiocytosis (LCH) stands as the most common histiocytic disorder. It is categorized into single-system single site, single-system multi-site, and multisystem types, with or without involvement of risk organs. Clinical presentation exhibits considerable variability, contingent upon the affected organ systems. Given its rarity, diverse locations, and varying severity, there are currently no established treatment guidelines for LCH. Case Presentation: We documented the case of a 5-month-old male diagnosed with Langerhans cell histiocytosis (LCH), presenting with high-risk multisystem organ involvement and concurrent unifocal bone involvement. Bone marrow aspiration revealed infiltration by multinucleated giant cells within the marrow. Skin biopsy demonstrated Langerhans cell proliferation with epidermotrophism and the characteristic reniform nucleus resembling a coffee bean. The patient was treated following the histiocytosis protocol, which included daily oral prednisone and 6-mercaptopurine, in addition to weekly intravenous vinblastine and methotrexate administered every two weeks. Unfortunately, the patient displayed limited response during the initial phase of treatment and, tragically, passed away during the eighth week of therapy. Conclusion: Langerhans cell histiocytosis (LCH) is a rare disease characterized by variable disease presentations and is associated with significant morbidity and mortality. Timely recognition of clinical manifestations and risk factors, coupled with appropriate treatment, is crucial to reduce mortality and long-term complications associated with the condition.

Vaccination after developing long COVID: Impact on clinical presentation, viral persistence, and immune responses

BackgroundVaccination protects against severe COVID-19 manifestations. For those with post-COVID-19 conditions (PCC) or long COVID, the impact of COVID-19 vaccination on the evolution of symptoms, immune responses, and viral persistence is unclear. MethodsIn this prospective observational cohort study, we evaluated the number of PCC symptoms, affected organ systems, and psychological well-being scores before and after patients with PCC received COVID-19 vaccination. We simultaneously evaluated biomarkers of systemic inflammation and levels of plasma cytokines/chemokines. We measured plasma and intracellular levels of SARS-CoV-2 antigens, and immunoreactivity to SARS-CoV-2 antigens in blood. ResultsCOVID-19 vaccination was associated with decreases in number of PCC symptoms (pre-vaccination: 6.56 ± 3.1 vs post-vaccination: 3.92 ± 4.02; P <0.001) and affected organ systems (pre-vaccination: 3.19 ± 1.04 vs post-vaccination: 1.89 ± 1.12; P <0.001), and increases in World Health Organization (WHO)-5 Well-Being Index Scores (pre-vaccination: 42.67 ± 22.76 vs post-vaccination: 56.15 ± 22.83; P <0.001). Patients with PCC also had significantly decreased levels of several pro-inflammatory plasma cytokines/chemokines after COVID-19 vaccination including sCD40L, GRO-⍺, macrophage inflammatory protein (MIP)-1⍺, interleukin (IL)-12p40, G-colony stimulating factor (CSF), M-CSF, IL-1β, and stem cell factor (SCF). PCC participants presented a certain level of immunoreactivity toward SARS-CoV-2, that was boosted with vaccination. SARS-CoV-2 S1 antigen persisted in the blood of PCC participants, mostly in non-classical monocytes, regardless of participants receiving vaccination. ConclusionsOur study shows higher pro-inflammatory responses associated with PCC symptoms and brings forward a possible role for vaccination in mitigating PCC symptoms by decreasing systemic inflammation. We also observed persistence of viral products independent of vaccination that could be involved in perpetuating inflammation through non-classical monocytes.

Cutaneous Adverse Drug Reactions to Antibiotics: How Much is the Extent of the Problem?

Medication-related harm or adverse drug reaction is a great global health concern today. They are frequent and, most often, devastating. With the rising incidences of drug-related adverse outcomes, it is imperative that clinicians have the knowledge and understanding of these occurrences to prevent, diagnose, and manage them properly. Skin is a very commonly affected organ system, and incidences of cutaneous adverse drug reactions are between 1-5% depending on the geographic location. Up to 60% or more of all adverse drug reactions may represent cutaneous reactions. These may fall into either of the dose-dependent or dose-independent categories. Being the most prescribed and utilized drug group, antibiotics have been implicated as one of the major drug groups causing cutaneous drug reactions. There is ample evidence that antibiotics cause severe and non-severe cutaneous adverse drug reactions. A review of the present literature was done using MEDLINE/PubMed, Google Scholar, and other search engines to gather evidence to find how extensive the problem is and how much the burden is. Which will enlighten clinicians from all backgrounds and medical students and help them deal with cutaneous adverse drug reactions more prudently

CD4 T cells and toxicity from immune checkpoint blockade.

Immune-related toxicities, otherwise known as immune-related adverse events (irAEs), occur in a substantial fraction of cancer patients treated with immune checkpoint inhibitors (ICIs). Ranging from asymptomatic to life-threatening, ICI-induced irAEs can result in hospital admission, high-dose corticosteroid treatment, ICI discontinuation, and in some cases, death. A deeper understanding of the factors underpinning severe irAE development will be essential for improved irAE prediction and prevention, toward maximizing the benefits and safety profiles of ICIs. In recent work, we applied mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, bulk RNA sequencing, and bulk T-cell receptor (TCR) sequencing to identify pretreatment determinants of severe irAE development in patients with advanced melanoma. Across 71 patients separated into three cohorts, we found that two baseline features in circulation-elevated activated CD4 effector memory T-cell abundance and TCR diversity-are associated with severe irAE development, independent of the affected organ system within 3 months of ICI treatment initiation. Here, we provide an extended perspective on this work, synthesize and discuss related literature, and summarize practical considerations for clinical translation. Collectively, these findings lay a foundation for data-driven and mechanistic insights into irAE development, with the potential to reduce ICI morbidity and mortality in the future.

Autoimmune bullous dermatoses in cancer patients treated by immunotherapy: a literature review and Italian multicentric experience.

Cutaneous immune-related adverse events are frequently associated with immune checkpoint inhibitors (ICIs) administration in cancer patients. In fact, these monoclonal antibodies bind the cytotoxic T-lymphocyte antigen-4 and programmed cell death-1/ligand 1 leading to a non-specific activation of the immune system against both tumoral cells and self-antigens. The skin is the most frequently affected organ system appearing involved especially by inflammatory manifestations such as maculopapular, lichenoid, psoriatic, and eczematous eruptions. Although less common, ICI-induced autoimmune blistering diseases have also been reported, with an estimated overall incidence of less than 5%. Bullous pemphigoid-like eruption is the predominant phenotype, while lichen planus pemphigoides, pemphigus vulgaris, and mucous membrane pemphigoid have been described anecdotally. Overall, they have a wide range of clinical presentations and often overlap with each other leading to a delayed diagnosis. Achieving adequate control of skin toxicity in these cases often requires immunosuppressive systemic therapies and/or interruption of ICI treatment, presenting a therapeutic challenge in the context of cancer management. In this study, we present a case series from Italy based on a multicenter, retrospective, observational study, which included 45 patients treated with ICIs who developed ICI-induced bullous pemphigoid. In addition, we performed a comprehensive review to identify the cases reported in the literature on ICI-induced autoimmune bullous diseases. Several theories seeking their underlying pathogenesis have been reported and this work aims to better understand what is known so far on this issue.

A STUDY TO ASSESS, MONITOR, AND REPORTING OF ADVERSE DRUG REACTIONS IN A TERTIARY CARE TEACHING HOSPITAL: HIMS, HASSAN

Objective: An adverse drug reaction (ADR) is an unwanted, undesirable effect of a medication that occurs during usual clinical use. ADR should be quickly identified and managed to limit their detrimental effects on the patient. This study was undertaken to characterize the pattern of ADRs reported through spontaneous reporting system at ADR reporting unit in a tertiary care teaching hospital. Methods: A prospective, observational study was conducted over 3 years between September, 2017 and August, 2019. The ADRs reported were from patients admitted inpatient department of hospital. Evaluation of patient demographics, drug and ADR characteristics, and outcome of the ADRs. Causality and severity assessment was done by the World Health Organization system and Naranjos scale. Results: 82 cases of ADRs were reported during the study period. More number of ADRs was from General Medicine and Pediatric departments, in which the most affected organ systems were the skin and the gastrointestinal tract. The antibiotic classes mostly accounted were cephalosporins. None of the ADR was fatal. Conclusion: ADRs to antibiotics are common and will be resulted in increased health-care cost due to the need of some interventions and increased length of hospital stay. The health-care system should promote proper documentation and periodic reporting to regional pharmacovigilance centers to ensure drug safety.

Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity

Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS. Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.

The distribution and accumulation of the shortest telomeres in telomere biology disorders.

Individuals with telomere biology disorders (TBDs) have very short telomeres, high risk of bone marrow failure (BMF), and reduced survival. Using data from TBD patients, a mean leukocyte Southern blot telomere length (TL) of 5 kilobases (kb) was estimated as the 'telomere brink' at which human survival is markedly reduced. However, the shortest telomere, not the mean TL, signals replicative senescence. We used the Telomere Shortest Length Assay (TeSLA) to tally TL of all 46 chromosomes in blood-derived DNA and examined its relationship with TBDs. Patients (n = 18) had much shorter mean TL (TeSmTL) (2.54 ± 0.41 kb vs. 4.48 ± 0.52 kb, p < 0.0001) and more telomeres <3 kb than controls (n = 22) (70.43 ± 8.76% vs. 33.05 ± 6.93%, p < 0.0001). The proportion of ultrashort telomeres (<1.6 kb) was also higher in patients than controls (39.29 ± 10.69% vs. 10.40 ± 4.09%, p < 0.0001). TeS <1.6 kb was associated with severe (n = 11) compared with non-severe (n = 7) BMF (p = 0.027). Patients with multi-organ manifestations (n = 10) had more telomeres <1.6 kb than those with one affected organ system (n = 8) (p = 0.029). Findings suggest that TBD clinical manifestations are associated with a disproportionately higher number of haematopoietic cell telomeres reaching a telomere brink, whose length at the single telomere level is yet to be determined.

Investigating the potential associated factors and developing a risk model for interstitial lung disease in Chinese patients with systemic lupus erythematosus.

This study aimed to explore the risk factors for interstitial lung disease (ILD) in Chinese patients with systemic lupus erythematosus (SLE). This study recruited 40 SLE patients with ILD (SLE-ILD) and 40 SLE patients without ILD (SLE-non-ILD). Clinical data were collected from all patients, including basic clinical characteristics, affected organ systems, biochemical indexes, autoantibodies, and immunocytes. Compared with the SLE-non-ILD patients, SLE-ILD patients presented older age (p < 0.001), dry cough (p = 0.006), "velcro-like" crackles (p = 0.021), Raynaud's phenomenon (p = 0.040), elevated complement 3 (C3) level (p = 0.044), and lower SLE disease activity index score (p = 0.013) and cluster of difference-3cell count (p = 0.043). Multivariate logistic regression analysis showed that older age (p < 0.001, odds ratio [OR]: 1.212), female sex (p = 0.022, OR: 37.075), renal involvement (p = 0.011, OR: 20.039), C3 level (p = 0.037, OR: 63.126), immunoglobulin (Ig) M level (p = 0.005, OR: 5.082), and positive anti-U1 small ribonucleoprotein antibody (anti-nRNP) result (p = 0.003, OR: 19.886) were independent ILD risk factors in SLE patients. Consequently, the ILD risk model in patients with SLE was constructed based on statistically significant variables from the multivariate logistic regression analysis, which significantly correlated with ILD risk, with an area under the curve of 0.887 (95% confidence interval: 0.815-0.960) using receiver operating characteristic curve analysis. Age, female sex, renal involvement, C3 level, IgM level, and a positive anti-nRNP result are independent risk factors for ILD. Furthermore, their combination model is closely associated with an increased ILD risk in Chinese patients with SLE.

Research of neutrophil-to-lymphocyte ratios and platelet-tolymphocyte ratios in systemic lupus erythematosus in Hue University of Medicine and Pharmacy Hospital

Background: Systemic lupus erythematosus (SLE) is a chronic systemic inflammatory autoimmune disease and has various clinical manifestations affecting organ systems. It is characterized by the deposition of immune complexes due to widespread loss of immune tolerance to nuclear self-antigens, as well as excessive proinflammatory cytokine production. The neutrophil-to-lymphocyte ratios (NLR) and platelet-tolymphocyte ratio (PLR) in SLE are often higher than in the normal population, which is significantly related to disease progression and is an indicator of monitoring disease activity. Therefore, the study was conducted with the aim of understanding the change of some hematological indexes in patients with SLE. Materials and method: The study was conducted on 51 patients with newly diagnosed SLE at the Department of General Internal Medicine - Endocrinology - Musculoskeletal and a control group of 30 healthy people who came to the hospital of Hue University of Medicine and Pharmacy from June 2022 to March 2023. Results: The NLR and PLR of SLE patients were significantly higher compared to those of the controls (p &lt; 0.001 and p &lt; 0.012, respectively). Based on the ROC curve, the best NLR cut-off value to predict SLE was 1.7 with 58.8% sensitivity and 70.0% specificity. NLR was positively correlated with PLR (r = 0.735, p &lt; 0.001) and white blood cells (r = 0.532, p &lt; 0.001). Conclusion: The NLR index can be a useful marker in the assessment of inflammation in patients with SLE Key words: Systemic lupus erythematosus, NLR, PLR.

Can Serum 25-Hydroxy Vitamin D Levels Predict the Severity of Multisystem Inflammatory Syndrome in Children and COVID-19?

To determine the clinical significance of serum 25-hydroxy (OH) vitamin D levels in pediatric patients with multisystem inflammatory syndrome in children (MIS-C) and compare the vitamin D levels of these patients with those patients with Coronavirus disease-2019 (COVID-19) and healthy controls. This study was designed for pediatric patients aged 1 month to 18 years and conducted between July 14 and December 25, 2021. Fifty-one patients with MIS-C, 57 who were hospitalized with COVID-19, and 60 controls were enrolled in the study. Vitamin D insufficiency was defined as a serum 25 (OH) vitamin D level of less than 20 ng/mL. Severe MIS-C was classified as necessitating intensive care due to cardiovascular instability, the necessity for non-invasive or invasive mechanical ventilation, and/or a diminishing Glasgow coma scale. World Health Organization definition criteria were used to describe the clinical stages of COVID-19 in children and patients were divided into four groups according to the clinical severity of COVID-19: asymptomatic, mild, moderate, and severe/critical. The median serum 25 (OH) vitamin D was 14.6 ng/mL in patients with MIS-C, 16 ng/mL in patients with COVID-19, and 21.1 ng/mL in the control group (p<0.001). Vitamin D insufficiency was present in 74.5% (n=38) of patients with MIS-C, 66.7% (n=38) of patients with COVID-19, and 41.7% (n=25) of the controls (p=0.001). The percentage of four or more affected organ systems was 39.2% in patients with MIS-C. The correlation between the number of affected organ systems and serum 25 (OH) vitamin D levels was evaluated in patients with MIS-C and there was a moderate negative correlation (r=-0.310; p=0.027). A weak negative correlation was found between the severity of COVID-19 and serum 25 (OH) vitamin D (r=-0.320, p=0.015). Vitamin D levels were insufficient in both the MIS-C and COVID groups. Furthermore, vitamin D levels correlated with the number of affected organ systems in MIS-C and the severity of COVID-19.

A Registry Study of 240 Patients with X-Linked Agammaglobulinemia Living in the USA

PurposeTo understand the natural history and clinical outcomes for patients with X-linked agammaglobulinemia (XLA) in the United States utilizing the United States Immunodeficiency Network (USIDNET) patient registry.MethodsThe USIDNET registry was queried for data from XLA patients collected from 1981 to 2019. Data fields included demographics, clinical features before and after diagnosis of XLA, family history, genetic mutation in Bruton’s tyrosine kinase (BTK), laboratory findings, treatment modalities, and mortality.ResultsData compiled through the USIDNET registry on 240 patients were analyzed. Patient year of birth ranged from 1945 to 2017. Living status was available for 178 patients; 158/178 (88.8%) were alive. Race was reported for 204 patients as follows: White, 148 (72.5%); Black/African American, 23 (11.2%); Hispanic, 20 (9.8%); Asian or Pacific Islander, 6 (2.9%), and other or more than one race, 7 (3.4%). The median age at last entry, age at disease onset, age at diagnosis, and length of time with XLA diagnosis was 15 [range (r) = 1–52 years], 0.8 [r = birth–22.3 years], 2 [r = birth–29 years], and 10 [r = 1–56 years] years respectively. One hundred and forty-one patients (58.7%) were < 18 years of age. Two hundred and twenty-one (92%) patients were receiving IgG replacement (IgGR), 58 (24%) were on prophylactic antibiotics, and 19 (7.9%) were on immunomodulatory drugs. Eighty-six (35.9%) patients had undergone surgical procedures, two had undergone hematopoietic cell transplantation, and two required liver transplantation. The respiratory tract was the most affected organ system (51.2% of patients) followed by gastrointestinal (40%), neurological (35.4%), and musculoskeletal (28.3%). Infections were common both before and after diagnosis, despite IgGR therapy. Bacteremia/sepsis and meningitis were reported more frequently before XLA diagnosis while encephalitis was more commonly reported after diagnosis. Twenty patients had died (11.2%). The median age of death was 21 years (range = 3–56.7 years). Neurologic condition was the most common underlying co-morbidity for those XLA patients who died.ConclusionsCurrent therapies for XLA patients reduce early mortality, but patients continue to experience complications that impact organ function. With improved life expectancy, more efforts will be required to improve post-diagnosis organ dysfunction and quality of life. Neurologic manifestations are an important co-morbidity associated with mortality and not yet clearly fully understood.

Tapping the hospital antimicrobial stewardship initiatives for monitoring antibiotics-related adverse drug reactions

Adverse drug reactions (ADRs) are harmful effects caused by medications. ADRs may have a significant impact on patients’ quality of life while additionally adding strain on the healthcare system. ADRs are one of the most common prevalent causes of morbidity globally, and they will continue to be a challenging public health issue as medication becomes more advanced to treat diverse diseases in a growing population. A retrospective observational study was carried out in one of the super speciality hospitals of a South Indian City on the antibiotic-associated ADRs reported from 2017 to 2023. Amongst 68 ADRs, 40 (59%) were found to be associated with antibiotics. These ADRs were associated equally in males 20 (50%) and females 20 (50%). The reactions were more in the age group &gt;50 years (n = 20, 50%), and lesser in children of 2–11 years (n = 6, 15%). A higher number of ADRs was caused by beta-lactam inhibitors (n = 13, 33%), followed by the quinolone group (n = 11, 28%). The severity of the reactions was found to be mild (n = 30, 75%) and severe (n = 1, 2.5%). The most affected organ system was the skin and cutaneous system. The results of the study highlight enhanced hospital pharmacovigilance monitoring of antibiotics-associated ADRs to ensure patient safety. Alternatively, hospital antimicrobial stewardship programs may lead a joint effort in preventing antibiotic-associated ADRs and multidrug-resistant infections.

Multiple time-dependent pathophysiological changes in a rabbit model of high-fat diet-induced hyperlipidemia.

High-fat diets (HFD) adversely affect organ systems. Several studies have examined HFD-related disorders in animals but only in a few organs and time points. Herein, we evaluated disease development with time-dependent HFD-induced pathological, cardiovascular, and morphological changes in rabbits with lipid metabolism similar to that in humans for 9 weeks. The body weights and waist ratio of the HFD group were higher than those in the control group. HFD significantly increased the total cholesterol, low-density lipoprotein, high-density lipoprotein, and phospholipid levels after 3 weeks. Liver enzyme levels increased with hepatomegaly, steatosis, and fibrosis after 3 or 6 weeks. RBCs and hemoglobin decreased, while platelets increased in the HFD group with atherosclerosis and inflammatory cell infiltration in the aorta after 6 weeks. Ejection fraction and fractional shortening values decreased in the HFD group after 9 weeks. Creatinine increased with glomerulosclerosis in the kidneys of the HFD groups after 3 weeks, indicating renal dysfunction. Lipid accumulation was found in the pancreas after 9 weeks. Lipid accumulation and hypertrophy were observed in the adrenal glands after 3 weeks. Overall, our findings provide global reference data on the time-dependent effects of HFD on the body and may serve as a guide for future HFD risk prevention.

Abstract 6670: Association between circulating CD4 memory T cell levels and severe immune-related adverse events in melanoma patients treated with immune checkpoint blockade

Abstract Introduction: Severe immune-related adverse events (irAEs) occur in up to 60% of melanoma patients treated with immune checkpoint inhibitors (ICIs), causing substantial treatment-related morbidity and in the most severe cases, death. There is no clinical assay to predict who will develop severe ICI-induced irAEs and who will not. Using single-cell profiling assays applied to a retrospective melanoma cohort treated with ICIs, we recently showed that higher baseline levels of circulating CD4 effector memory T (TEM) cells were associated with severe irAE development, independent of the affected organ system (Lozano et al. Nature Medicine, 2022). As part of a prospective validation study of 100 melanoma patients, here we report our initial findings on the first 24 patients accrued to date. Methods: We prospectively collected pre-ICI blood from 24 metastatic melanoma patients from two academic medical centers from February 2021 onward. Peripheral blood was collected pre-treatment on the day of immunotherapy (cycle 1 day 1). We then isolated peripheral blood mononuclear cells (PBMCs) and applied mass cytometry by time of flight (CyTOF) to profile 38 leukocyte markers including markers specific to CD4 TEM cells. Cellular subpopulations were quantified using Cytobank v9. Patients underwent routine medical oncology follow-up during and after ICI treatment including grading of irAEs using the Common Terminology Criteria for Adverse Events v5. Results: Median follow-up time after pre-ICI blood collection was 9.1 months (range 2.6-18.5). Fifteen (63%) patients received combination (anti-PD1/anti-CTLA4) ICIs while the remainder received anti-PD1 monotherapy. Eight patients developed severe (grade 3+) irAEs at a median of 8.5 weeks (range 4-21) after treatment initiation, including 4 who developed life-threatening (grade 4) irAEs. Severe and life-threatening irAE development spanned 9 separate organ systems, most commonly gastrointestinal, dermatological, and hepatic. Using CyTOF, we found that circulating CD4 TEM cells were more abundant in patients who developed severe irAEs compared to those who did not (P = 0.01; AUC = 0.81), irrespective of the involved organ systems. Moreover, median-splitting the patient cohort into two groups based on pretreatment CD4 TEM levels revealed that patients with low CD4 TEMs had significantly longer freedom from severe irAE than those with high CD4 TEMs (not reached vs. 4.6 months; P = 0.013; HR = 6.7). There was no significant difference in pretreatment CD4 TEM levels between patients with and without durable clinical benefit to ICIs (P = 0.75). Conclusion: Circulating CD4 TEM levels measured by CyTOF were associated with severe irAE development, independent of response status, in patients with advanced melanoma. These findings could form the basis for pretreatment ICI risk stratification in the future. Citation Format: Abul Usmani, Noah Earland, Wubing Zhang, Peter K. Harris, Antonietta Bacchiocchi, Aishwarya Nene, David Y. Chen, Mario Sznol, Ruth Halaban, Aaron M. Newman, Aadel A. Chaudhuri. Association between circulating CD4 memory T cell levels and severe immune-related adverse events in melanoma patients treated with immune checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6670.

58 Utilizing VA Data to Define Long COVID and Identify Patients at Risk

OBJECTIVES/GOALS: To determine the signs, symptoms, and diagnoses that are significantly upregulated in cases of long COVID while identifying risk factors and demographics that increase one’s likelihood of developing long COVID. METHODS/STUDY POPULATION: This is a retrospective, big data science study. Data from Veterans Affairs (VA) medical centers across the United States between the start of 2020 and the end of 2022 were utilized. Our cohort consists of 316,782 individuals with positive COVID-19 tests recorded in the VA EHR with a history of ICD10-CM diagnosis codes in the record for case-control comparison. We looked at all new diagnoses that were not present in the six months before COVID diagnosis but were present in the time period from one month after COVID through seven months after. We determined which were significantly enriched and calculated odds ratios for each, organized by long COVID subtypes by medical specialty / affected organ system. Demographic analyses were also performed for long COVID patients and patients without any new long COVID ICD10-CM codes. RESULTS/ANTICIPATED RESULTS: This profile shows disorders that are highly upregulated in the post-COVID population and provides strong evidence for a broad definition of long COVID. By breaking this into subtypes by medical specialty, we define cardiac long COVID, neurological long COVID, pulmonary long COVID, and eight others. The long COVID cohort was older with more comorbidities than their non-long COVID counterparts. We also noted any differences regarding sex, race, ethnicity, severity of acute COVID-19 symptoms, vaccination status, as well as some analysis regarding medications taken. DISCUSSION/SIGNIFICANCE: This profile can be utilized to decisively define long COVID as a clinical diagnosis and will lead to consistence in future research. Elucidating an actionable model for long COVID will help clinicians identify those in their care that may be experiencing long COVID, allowing them to be admitted into more intensive monitoring and treatment programs.

BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme.

To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme. The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups. The four commonly affected organ systems were the digestive (liver only) (82%), respiratory (76%), gastrointestinal (65%) and reticuloendothelial (42%). There were significant differences in the pattern of metastatic breast cancer in BRCA1/2 germline carriers compared with non-carriers. Breast cancer carriers had significantly fewer organ systems involved (median n=3, range=1-3) compared with non-carriers (median n=9, range=1-7) (P=0.03). BRCA1/2 carriers with ovarian carcinomas had significantly more organ systems with metastatic carcinoma (median n=10, range=3-8) than non-carriers (median n=5, range=3-5) (P < 0.001). There were no significant differences in the number of involved systems in BRCA2 carriers compared with non-carriers with prostate cancer (P=1.0). There was an absence of locoregional disease (6.5%) compared with distant disease (93.5%) among the three cancer subtypes (P < 0.001). The majority of metastatic deposits (97%) collected during the autopsy were identified by recent diagnostic imaging. Even though a major limitation of this study is that our numbers are small, especially in the breast cancer carrier group, the metastatic patterns of breast and ovarian cancers may be impacted by BRCA1/2 carrier status, suggesting that tumours derived from patients with these mutations use different mechanisms of dissemination. The findings may focus clinical diagnostic imaging for monitoring metastases where whole-body imaging resources are scant.

MORBIDITY AND MORTALITY OF BINTURONGS (ARCTICTIS BINTURONG) IN UNITED STATES ZOOLOGICAL INSTITUTIONS (1986-2019).

Veterinary literature on diseases in binturong (Arctictis binturong) is often limited to case series or reports without population-level information. Morbidity and mortality data were collected from North American institutions through survey completion or submission of medical records. Responses included information about 74 individuals (37 males, 30 females, and 7 unknown neonates) representing 22 institutions, from 1986 to 2019. Antemortem data were available from 39 individuals, and postmortem data were available from 53 individuals. Eighteen individuals had both antemortem and postmortem records available. Age (mean ± SD) at death for adults (n = 41) was 15.2 ± 4.3 yr. Morbidity events were summarized by affected organ system; 160 events were reported. The systems with the most frequently reported events were gastrointestinal (33%; 53/160), integumentary (19%; 31/160), urinary (12%; 20/160), and musculoskeletal (19 [12%] of 160). Excluding neonates, primary causes of mortality included neoplasia (51%; 21/41), infectious or inflammatory diseases (24%; 10/41), and cardiovascular disease (17%; 7/41). Neoplasms (51%; 21/41) confirmed on histopathology included renal adenocarcinoma (47%; 10/21); mammary carcinoma (14%; 3/21); pancreatic islet cell carcinoma (2 [10%] of 21); and single instances of multicentric lymphoma, uterine carcinoma, and submucosal urethral adenoma. There were three additional cases of presumed neoplasia without histopathologic confirmation; masses were detected in the liver, heart base, and pancreas. Metastases were reported in 15 (71%) of 21 neoplasms. Although neoplasia and cardiovascular disease were common causes of mortality, they were rarely diagnosed antemortem. Neoplasia was often malignant and generally diagnosed after metastasis. Preventive medicine protocols with improved renal and cardiovascular evaluation are warranted and may result in earlier detection of subclinical disease in binturong.

English

Introduction: Several international sports federations have implemented a standardized injury registration system during their championships. However, very few studies have included athletes with disabilities during major competitions, apart from the Paralympic Games. Therefore, the objective of this study is to evaluate the rate and characteristics of illnesses and injuries during the 2021 South America Wheelchair Basketball Championships. Material and method: The coaching staff of the 11 participating teams (a total of 129 players) were asked to report daily all the health problems that have occurred and their characteristics in a standardized form. Prevalence and incidence rates were calculated. Results: In this study 108 health problems were reported, equivalent to 83.7 per 100 players [95% CI: 67.9-99.5], with 8 timeloss health problems (6.2 per 100 players [95% CI: 1.9-10.5]) and a total of 74 medical attention injuries (57.4 per 100 players [95% CI:44.3-70.4]). Were reported 15 diseases, and the most affected organ systems were ophthalmologic, gastrointestinal, and genitourinary. More injuries were recorded during matches (n=43). The most affected regions were shoulder/clavicle (24.7%), hand/fingers (23.7%) and neck/cervical spine (12.9%). The most frequent conditions were muscle contractures/cramps (32.2%), and the predominant mechanism was overuse (53.8%). 2.2% of concussions produced during training were reported. Most of the recorded events were without time loss and with return to full participation between zero and one day. Conclusion: Monitoring of health problems during competitions is essential to determine sport-specific injury risk factors, and a complex approach should be implemented for the recognition of their characteristics in wheelchair basketball players. In this way, adequate preventive measures can be developed.

Chlorine gas hazardous material incident in Karachi, Pakistan: A clinical experience from an emergency department of a tertiary care hospital.

To determine the clinical characteristics, management and outcomes of patients presenting with chlorine gas exposure in an emergency setting. The single-centre, retrospective cross-sectional study was conducted at the emergency department of Aga Khan University Hospital, Karachi, and comprised data of all patients who presented on March 06, 2020, due to acute chlorine gas exposure after a specific industrial accident. Demographic and clinical data was recorded from the medical record files. The association between risk factors and complications was explored. Data was analysed using SPSS 20. There were 51 male patients with a mean age of 33.10±8.37 years. The most commonly affected organ system was respiratory 49(96%), with 43(84.3) having shortness of breath. Eye irritation was found in 44(86.3%) cases and the central nervous system was involved in 14(27.4%). Most of the patients were admitted from the emergency department 36(70%). Regarding treatment, 1(1.9%) patient each required invasive and non-invasive mechanical ventilation. Complications included toxic pneumonitis 3(5.9%) and pneumomediastinum 1(1.7%). No correlation was found between smoking and complications (p>0.05). Most patients showed complete resolution of symptoms after receiving supportive treatment, while complications were rare and there was no mortality.