Severe Clinical Presentation Research Articles

Morphological changes in hematopoietic parameters in COVID-19 and their prognostic significance

The types of morphological changes in the complete blood count, along with other laboratory parameters, can help establish the severity of the condition and provide the prognostic value in determining the survival of a patient with COVID-19. Peripheral blood smear (PBS) examination is a routine and simple procedure that can be performed at any medical institution. However, data on morphological changes in PBS during COVID-19 are still insufficient. Therefore, it is relevant to identify the features and patterns of these changes, taking into account the severity of the clinical presentation of COVID-19, and establish their prognostic significance. The aim. To review the literature on the presence of morphological changes in hematopoietic parameters in the case of SARS-CoV-2 infection with respect to the disease course.Results and Conclusions. Morphological changes in at least one blood cell lineage were observed in all cases of SARS-CoV-2 infection. The most common are nuclear and cytoplasmic disorders of neutrophils, such as hypogranulation and hypo/hypersegmentation of neutrophil nuclei, often with toxogenic stippling. Typical changes in lymphocyte morphology include monocytoid, lymphoplasmacytoid, granular, and atypical cells with nucleoli. Prognostically unfavorable morphological signs in the PBS include giant neutrophils and their toxic granulation, plasmacytization of lymphocytes, and a dynamic decrease in granular and abnormal lymphocytes and monocytes. A low count of lymphocytes and their subpopulations is associated with a severe clinical presentation and an unfavorable outcome of COVID-19 disease, which suggests the feasibility of their immunophenotypic evaluation and monitoring. The detection and serial monitoring of inflammatory monocytes using flow cytometry may be valuable in predicting the course and choosing adequate therapy for SARS-CoV-2 infection. Additionally, an increase in the red cell distribution width was also shown to have prognostic importance.

Clinical features and 28-day mortality predictors of vaccinated patients admitted to a COVID-19 ICU hub in Italy

BackgroundCOVID-19 vaccination has been proved to be effective in preventing hospitalization and illness progression, even though data on mortality of vaccinated patients in the intensive care unit (ICU) are conflicting. The aim of this study was to investigate the characteristics of vaccinated patients admitted to ICU according to their immunization cycle and to outline the risk factors for 28-day mortality. This observational study included adult patients admitted to ICU for acute respiratory failure (ARF) due to SARS-CoV-2 and who had received at least one dose of vaccine.ResultsFully vaccination was defined as a complete primary cycle from < 120 days or a booster dose from > 14 days. All the other patients were named partially vaccinated. One-hundred sixty patients (91 fully and 69 partially vaccinated) resulted eligible, showing a 28-day mortality rate of 51.9%. Compared to partially vaccinated, fully vaccinated were younger (69 [60–77.5] vs. 74 [66–79] years, p 0.029), more frequently immunocompromised (39.56% vs. 14.39%, p 0.003), and affected by at least one comorbidity (90.11% vs 78.26%, p 0.045), mainly chronic kidney disease (CKD) (36.26% vs 20.29%, p 0.035). At multivariable analysis, independent predictors of 28-day mortality were as follows: older age [OR 1.05 (CI 95% 1.01–1.08), p 0.005], history of chronic obstructive pulmonary disease (COPD) [OR 3.05 (CI 95% 1.28–7.30), p 0.012], immunosuppression [OR 3.70 (CI 95% 1.63–8.40), p 0.002], and admission respiratory and hemodynamic status [PaO2/FiO2 and septic shock: OR 0.99 (CI 95% 0.98–0.99), p 0.009 and 2.74 (CI 95% 1.16–6.48), p 0.022, respectively].ConclusionsDespite a full vaccination cycle, severe COVID-19 may occur in patients with relevant comorbidities, especially immunosuppression and CKD. Regardless the immunization status, predisposing conditions (i.e., older age, COPD, and immunosuppression) and a severe clinical presentation were predictors of 28-day mortality.

The laboratory parameters and scoring systems used to predict clinical outcomes in geriatric patients with acute pancreatitis.

Acute pancreatitis (AP) is the leading cause of hospital admissions among gastrointestinal system disorders, and it can resolve independently or lead to life-threatening multiple organ failure. Acute pancreatitis can have a more severe clinical presentation in geriatric patients as compared to younger patients. In this study, we aimed to elucidate the clinical and laboratory characteristics of patients aged 65 and older who presented to the emergency department with a diagnosis of AP and assessed their impact on hospital stay, in-hospital mortality, and cost. We reviewed the records of patients aged 65 and older who presented to the emergency department and had lipase levels measured as exceeding three times the upper limit of the reference range during the evaluation. We recorded these patients' vital signs, medical histories, laboratory values, and etiologies. Using these data, we calculated the patients' clinical scores. We recorded data on 218 patients who met the inclusion criteria. The median age of the patients was 76 (65-113). Of these, 70.6% were females, 54.6% had gallstones, 90.4% (n = 197) were admitted to the general ward from the emergency department, and 7.3% (n = 16) were admitted to the intensive care unit (ICU). In-hospital mortality was 5.63% (n = 12). The Ranson, Glasgow Severity Score (GSS), and Bedside Index for Severity in Acute Pancreatitis (BISAP) scores, as well as lactate, procalcitonin, and the lymphocyte-albumin ratio, were independent predictors of ICU admission and mortality. The early diagnosis of AP is essential. When a severe disease course is likely, initiating treatment promptly becomes crucial, especially in patients aged 65 and older. This approach can lead to significant reductions in both complication rates and treatment costs.

Abstract 129: Endovascular Therapy in Cerebral Venous Thrombosis: Nationwide Insights and Implications for Mortality

Introduction Cerebral Venous Thrombosis (CVT) is a rare cerebrovascular condition causing death or functional dependency in 10‐15%. Although Endovascular Therapy (EVT) is deployed variably across centers for managing CVT, the determinants and consequences of such use remain under‐explored. We examined the demographic and clinical correlates of EVT use in CVT and assessed its impact on patient outcomes utilizing a national database. Methods We identified CVT cases from 2015 to 2020 in the National Inpatient Sample, with EVT as the primary exposure. CVT and other diagnoses, and EVT and other procedures, were identified using standard ICD 10 codes. A backward stepwise regression model (at p&lt;0.05) was used to explore patient demographics, hospital characteristics, and comorbidities significantly associated with EVT use. We examined the association between EVT use and in‐hospital mortality using survey weighted unadjusted and adjusted logistic regression models. Covariates in the model one assessing inpatient mortality included age, insurance status, hospital teaching status, hospital volume size, central nervous system (CNS) infections, CNS cancer, other types of cancer, hematological disorder, traumatic head injuries, seizure, intubation, and transfer from an outside hospital. Model two additionally adjusted for female sex, NIH Stroke Scale (NIHSS), and Elixhauser mortality index. Results We identified 48,835 individuals with CVT, of whom 1,275 (2.6%) underwent EVT. The stepwise regression analysis revealed a higher likelihood of receiving EVT with older age (OR per year: 1.01, 95% CI: 1.01‐1.02, p&lt;0.001), presence of a hematological disorder (OR: 2.06, 95% CI: 1.58‐2.67, p&lt;0.001), seizure (OR: 1.54, 95% CI: 1.09‐2.16, p=0.014), intubation (OR: 3.85, 95% CI: 2.78‐5.34, p&lt;0.001), higher NIHSS (10.5[4‐18] versus 3[1‐8], p&lt;0.001), or admission to a teaching hospital (OR: 4.15, 95% CI: 1.93‐8.92, p&lt;0.001), high‐volume center (OR: 6.30, 95% CI: 2.29‐17.33, p&lt;0.001), or transfer from an outside hospital (OR: 1.89, 95% CI: 1.42‐2.51, p&lt;0.001). Conversely, there was a lower likelihood of EVT in those with CNS infections (OR: 0.19, 95% CI: 0.07‐0.48, p=0.001), CNS cancer (OR: 0.24, 95% CI: 0.06‐0.93, p=0.039), other types of cancer (OR: 0.47, 95% CI: 0.32‐0.69, p&lt;0.001), and traumatic head injuries (OR: 0.41, 95% CI: 0.25‐0.68, p&lt;0.001). Individuals with Medicare (OR: 0.39, 95% CI: 0.26‐0.59, p&lt;0.001) or Medicaid insurance (OR: 0.70, 95% CI: 0.50‐0.99, p=0.041), were also less likely to undergo EVT. EVT was associated with an increased odds of in‐hospital mortality (OR: 4.01, 95% CI 2.82‐5.68, p&lt;0.001), a relationship that persisted even after multivariable adjustment with model one (adjusted OR: 2.37 95% CI 1.50‐3.74, p&lt;0.001) and model two (adjusted OR: 7.32 95% CI 2.62‐20.5, p&lt;0.001). Conclusion We identified specific demographic and clinical factors associated with EVT use in CVT and found EVT use linked to higher mortality. The directionality of this relation is uncertain but could suggest more frequent use of EVT in individuals with very severe clinical presentations. These findings underscore the need for further prospective work to assess which individuals may benefit from therapy, in addition to optimal timing and approaches.

A Comparative Study of Women With Substance Use Disorder With and Without Post-traumatic Stress Disorder: Complex Interaction Between Childhood Trauma, Empathy, Personality Traits, and Substance Use Severity.

Substance use disorders (SUDs) and post-traumatic stress disorder (PTSD) significantly coexist; thus, identifying potential related factors of both illnesses is important for advancing the prevention strategies. The goals of this study were to compare women with SUD with and without PTSD in terms of potentially related variables and to investigate if those factors are associated with SUD severity. Ninety-five participants (women) with SUD who had been admitted to the outpatient treatment clinic in Turkey were assessed with borderline personality questionnaire, childhood trauma questionnaire, addiction profile index, Levenson self-report psychopathy questionnaire, and basic empathy scale. Participants with PTSD had significantly higher severity of addiction, childhood trauma, borderline personality traits, secondary psychopathy scores, and affective empathy scores than participants without PTSD (P = .013, P = .012, P = .008, P = .031, P = .040). Our study suggested that comorbid PTSD and SUD resulted in more complicated presentation. It seems to be crucial for practitioners to screen PTSD symptoms in women with severe SUD and complicated clinical presentations.

Overnight Melatonin Concentration and Sleep Quality Are Associated with the Clinical Features of Polycystic Ovary Syndrome.

Circulating melatonin is elevated in women with polycystic ovary syndrome (PCOS); whether circadian disruptions coincide with sleep disturbances in women with PCOS or their symptom severity is unclear. The objective of this observational pilot study was to determine whether altered patterns of melatonin excretion are associated with reduced sleep quality in women with versus without PCOS. Participants underwent a clinical assessment, transvaginal ultrasound, and reproductive hormone testing. Morning and evening urine samples were assayed for urinary 6-sulfatoxymelatonin (MEL) as a proxy for melatonin production. The night (morning MEL)-to-day (evening MEL) ratio, or N:D ratio, was determined to approximate the rhythm of MEL production. Sleep quality and duration were assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist actigraphy. No differences were detected in overnight MEL, daytime MEL, or the N:D ratio in participants with PCOS versus controls. The PCOS group experienced reduced weekend sleep efficiency vs. controls (81% vs. 88% p < 0.05). The number of follicles per ovary (FNPO) was positively associated with overnight MEL (r = 0.359, p < 0.05). Weekend sleep time and overnight MEL concentrations were dependent on PCOS status. Therefore, diagnostic features of PCOS were associated with MEL production and sleep disturbances, suggesting that women with a more severe clinical presentation of PCOS may be more likely to experience altered MEL production or sleep disturbances.

Combined Oxidative Phosphorylation Deficiency Type-13 with Perinatal Presentation: A Case Report.

Polynucleotide phosphorylase is involved in RNA processing in mitochondria. Biallelic variants in PNPT1 cause mitochondrial RNA import protein deficiency and heterogeneous clinical manifestations. The patiest was the first child of remote consanguineous parents, born at 35 weeks by caesarean section due to fetal growth restriction. Apgar index was 9/10/10. Birth weight, length and head circumference were at 3rd, <3rd and 10th percentiles, respectively. In the first hours of life, respiratory distress, hypoglycaemia and seizures ensued. She started invasive mechanic ventilation, phenobarbital and was transferred to ICU. Physical examination showed minor facial dysmorphisms, brief eye-opening, hypotonia and hyporeflexia. Electroencephalogram showed immature pattern and multifocal paroxysmal activity. MRI at D8 of life showed severe reduced brain volume. Normal aminoacid screen was also observed. Expanded newborn screening was negative. Mitochondrial organic aciduria was seen. WES showed a homozygotic likely pathogenic variant in the PNPT1 gene. MRI at 6-months showed brain atrophy, thin corpus callosum, reduced brainstem volume. Bilateral and symmetrical lesions in globi pallidi, compatible with Leigh síndrome were observed. Currently, at 14 months, no neurodevelopment progress, dystonia, visual deficit, sensorineural deafness, hypertrophic cardiomyopathy and microcephaly are observed. The early and severe Leigh-like presentation of our patient expands the phenotype spectrum of this disease. As far as we know, this is the first reported case of PNPT1 mutation with onset in the perinatal period. Moreover, hypertrophic cardiomyopathy has not yet been described in association with mutation of the PNPT1 gene. WES was the key for early diagnosis in this patient. It should be done in all children with severe clinical presentation of unknown origin.

Analysis of clinical phenotype and gene mutation characteristics of MYH9-related disorder

Objective: To investigate the clinical phenotype and gene mutation characteristics of MYH9-related disorder (MYH9-RD). Methods: The clinical data of 66 patients with MYH9-RD in the First Affiliated Hospital of Soochow University from January 2010 to December 2022 were retrospectively analyzed. According to the bleeding symptom, the patients were divided into bleeding and non-bleeding group, and according to the mutation sites, the patients were divided into non-muscle myosin heavy chain ⅡA head region (MD) and tail region (TD) mutation group. Statistical analysis was made to explore the clinical features in different groups such as platelet counts, bleeding, renal function, cataracts and hearing as well as MYH9 gene mutations. Results: A total of 66 MYH9-RD patients were included, with 28 males and 38 females, diagnosis age of 1-63(26±2) years. And 41% (27/66) of the patients had no family history. All patients presented with macrothrombocytopenia and normal platelet aggregation(10/10), 92% (54/59) of the patients had visible blue inclusion bodies in neutrophils, 30% (20/66) had bleeding symptoms, 45% (22/49) had proteinuria or glomerulonephropathy, 20% (8/41) had bilateral hearing impairment, and 10% (4/42) had bilateral cataracts. 18 mutation sites were identified in total, including 15 missense, 1 splicing and 2 termination mutations. Among them, p.Asp1424Asn, p.Arg1933* and p.Arg702His/Cys mutations were identified in 56% (29/52) of the patients, and p.Ser96Leu, Arg1165Cys and p.Glu1841Lys mutations were recurrent mutations, while p.Ala44Thr, p.Asp1447Ala and c.3838-2A>G mutations were novel mutations. The average platelet count of patients in bleeding group was (19±3)×109/L, which was significantly less than (36±3)×109/L in non-bleeding group (P<0.001). Compared with TD mutation group, patients of MD mutation group were presented with lower platelet count and higher risk of bleeding, as well as more severe clinical presentations including renal and hearing impairment and cataracts (all P<0.05). Conclusion: Mutations of p.Asp1424Asn, p.Arg1933* and p.Arg702His/Cys in MYH9 gene are hotspot mutations for MYH9-RD patients, Compared with TD mutation group, patients of MD mutation group were presented with lower platelet count and higher risk of bleeding, as well as more severe clinical presentations including renal and hearing impairment and cataracts.

Elevated serum levels of the NLRP3 inflammasome are associated with the severity of anti-NMDAR encephalitis in children

BackgroundAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common autoimmune encephalitis, mainly impacting young females and children. The involvement of the Nod-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and related cytokines in pediatric individuals with this condition remains unclear. MethodsWe collected information from 27 children who had anti-NMDAR encephalitis and 12 individuals with non-inflammatory neurological disorders as controls. We used an enzyme-linked immunosorbent assay (ELISA) to identify NLRP3 inflammasome, interleukin (IL)-1β, and IL-18 expression in cerebrospinal fluid (CSF) and matching serum samples. The modified Rankin Scale (mRS) score was performed throughout the acute phase and at the 6-month follow-up to determine the severity of the disease. The area under the curve (AUC) of the receiver operating characteristic curve was utilized to calculate the prediction efficacy. ResultsWhen compared to controls, individuals with anti-NMDAR encephalitis had significantly increased serum expression of the NLRP3 inflammasome (p < 0.001), IL-1β (p < 0.05), and IL-18 (p < 0.01). In the acute phase, mRS scores were correlated positively with serum levels of NLRP3 inflammasome (p = 0.008), IL-1β (p = 0.023), and IL-18 (p < 0.001). A positive connection was also found between serum levels of NLRP3 inflammasome and IL-1β (p = 0.005). Furthermore, the expression of IL-1β and IL-18 in serum correlated with the 6-month follow-up outcome. The AUC for NLRP3 inflammasome in distinguishing patients with severe neurologic impairments from those with moderate impairments was 0.808 (95 % CI: 0.645–0.972). ConclusionIn our investigation, children with anti-NMDAR encephalitis have more severe first clinical presentations when their serum concentrations of the NLRP3 inflammasome and related cytokines were higher. These findings provide a potential role for the NLRP3 inflammasome pathway in the pathogenesis of NMDAR encephalitis and provide a basis for targeted therapeutic interventions.

SAT187 A Case Of CDC73 Mutation Related Primary Hyperparathyroidism With Ectopic Parathyroid Hyperplasia

Abstract Disclosure: T. Wu: None. N. Dhir: None. M. Bollineni: None. Introduction: Primary hyperparathyroidism is the most common cause of hypercalcemia, and most cases are sporadic. However, in 5-10% cases, it may occur as a syndromic and hereditary disease, like Multiple endocrine neoplasia type 1, type 2A, type 4, or CDC73 mutation related hereditary benign or malignant hyperparathyroidism. In patients with severe or early onset primary hyperparathyroidism, screening for genetic etiology should be considered. Case Presentation: A 35-year-old woman with a medical history of hypertension, kidney stones, and post-operative hypothyroidism presented to the endocrinology clinic due to recurrent hyperparathyroidism. She initially had a parathyroidectomy in 2008 and her calcium corrected at that time. She was again diagnosed with hypercalcemia due to primary hyperparathyroidism in 2021. She underwent re-exploration and had a right thyroid lobectomy with removal of three parathyroid glands. Her PTH was still 309 pg/mL (9-77 pg/mL) and calcium was 11.2 mg/dL (8.6-10.5 mg/dL), and she was started on Cinacalcet. The patient continued to have elevated calcium, bone pain, fatigue, and constipation. A 4D CT scan was ordered, which localized activity to a 1.5 cm arterial enhancing nodule in the anterior mediastinum, with intrathymic location. She underwent right video-assisted thoracoscopic total thymectomy with en bloc and the nodule was found to be ectopic parathyroid tissue. Post-operatively, her calcium normalized to 8.6 mg/dL and PTH was undetectable. She underwent genetic testing due to her recurrent hyperparathyroidism, which showed a CDC73 mutation. She is currently on calcitriol and calcium supplements, and serum calcium has been maintained in the low-normal range. Discussion: The CDC73 gene encodes a protein called parafibromin, which acts as a tumor suppressor, prohibiting cells from proliferating. Mutations in this gene are linked to jaw-tumor syndrome, familial isolated primary hyperparathyroidism (FIHP), and parathyroid carcinoma. These three CDC73-related disorders are clinically overlapping and inherited in an autosomal dominant manner. Biallelic mutations of the CDC73 gene are associated with a high risk of parathyroid cancer since the parafibromin protein is usually absent in parathyroid carcinoma and occasionally in atypical adenomas. FIHP tends to have a more severe clinical presentation with earlier onset (younger than 45 years). Additionally, patients with CDC73 related disorders are more prone to developing ossifying fibroma(s) of the jaw, uterine tumors, and various renal lesions. In summary, this case highlights the diagnostic and therapeutic challenges in a patient with persistent primary hyperparathyroidism after a failed second surgery. Genetic testing is vital for early detection, surveillance, and familial genetic counseling in patients with CDC73 related disorders. Presentation: Saturday, June 17, 2023

SAT364 A Rare Cause of Hyperandrogenism in a Premenopausal Woman

Abstract Disclosure: L. El Musa Penna: None. W. Medina-Torres: None. L.R. Sepulveda-Garcia: None. L.N. Madera Marin: None. A. Rosado-Burgos: None. M.A. Ortiz-Rivera: None. B. Torres Rivera: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. M. Marcos Martínez: None. M. Correa Rivas: None. N. Bracero, MD: None. Hyperandrogenism in premenopausal women is most commonly associated to polycystic ovarian syndrome (PCOS). Approximately 10% of females in reproductive age present with clinical and/or biochemical findings of androgen excess, such as hirsutism, acne, alopecia, oligo-amenorrhea or if hyperandrogenism is severe it can lead to extreme virilization. Androgen excess can also contribute to insulin resistance. In this case we discuss a patient with severe hyperandrogenism, extreme insulin resistance and a rare cause of androgen excess in a woman of childbearing age. 34-year-old female patient G0P0 with type 2 diabetes mellitus (T2DM) on continuous insulin infusion system (CIIS), familial partial lipodystrophy, PCOS and severe hyperandrogenism, who was referred to our clinics for management of uncontrolled T2DM. Patient was on CIIS with regular insulin U-500 using a total daily dose of 95 units. She referred amenorrhea for the past 12 years and significant progression of hirsutism, alopecia and acanthosis nigricans in the past two years. Patient had clinical findings of hyperandrogenism such as hirsutism evaluated with modified Ferriman-Gallwey scale with a score of 32, alopecia Ludwig class 3 and marked acanthosis nigricans in neck and abdomen.Pre-operative laboratories: hemoglobin (Hgb) level 15.13 g/dL, hematocrit (Ht) 44.59 %, total testosterone level 525 ng/dL (13-53 ng/dL) and DHEAS 113 ug/dL (95.8-511.7 ug/dL), suggesting an ovarian source of androgen excess. Transvaginal ovarian ultrasound showed at the posteromedial edge of right ovary a hyperechoic structure measuring 1.5 cm long x 1.0 cm AP representing a lesion of unknown etiology. After discussion with patient a decision for oophorectomy was made. Pathology report described the ovary negative for neoplasia with findings consistent with hyperthecosis. Laboratories two weeks post-operative showed significant decrease in total testosterone to 81 ng/dL and in Hgb/ Ht (12.50 g/dL and 37.8% respectively). Insulin requirement decreased and she was able to be transitioned to U-100 insulin lispro with a total daily dose of 100. Four weeks after surgery patient had her menstrual period. Ovarian hyperthecosis is a disorder where there is an increased tissue with luteinized theca cells in the ovarian stroma; these cells are ovarian interstitial cells that differentiate into steroidogenically active cells. It is most commonly observed in post-menopausal women, but it has been described in women of childbearing age presenting with worsening hirsutism, virilization and insulin resistance. Monitoring patterns and progression of androgen excess is important in premenopausal women with a diagnosis of PCOS. Severe biochemical or clinical presentation, as well as progression of hyperandrogenism should increase suspicion of additional pathological entities as it will improve patient’s quality of life with the appropriate management. Presentation Date: Saturday, June 17, 2023

Global disparities in availability of epinephrine auto-injectors

BackgroundAnaphylaxis is the most severe clinical presentation of acute systemic allergic reactions and can cause death. Given the prevalence of anaphylaxis within healthcare systems, it is a high priority public health issue. However, management of anaphylaxis – both acute and preventative – varies by region. MethodsThe World Allergy Organization (WAO) Anaphylaxis Committee and the WAO Junior Members Steering Group undertook a global online survey to evaluate local practice in the diagnosis and management of anaphylaxis across regions. ResultsResponses were received from WAO members in 66 countries. While intramuscular epinephrine (adrenaline) is first-line treatment for anaphylaxis, some countries continue to recommend alternative routes in contrast to guidelines. Epinephrine auto-injector (EAI) devices, prescribed to individuals at ongoing risk of anaphylaxis in the community setting, are only available in 60% of countries surveyed, mainly in high-income countries. Many countries in South America, Africa/Middle-East and Asian-Pacific regions do not have EAI available, or depend on individual importation. In countries where EAIs are commercially available, national policies regarding the availability of EAIs in public settings are limited to few countries (16%). There is no consensus regarding the time patients should be observed following emergency treatment of anaphylaxis. ConclusionThis survey provides a global snapshot view of the current management of anaphylaxis, and highlights key unmet needs including the global availability of epinephrine for self-injection as a key component of anaphylaxis management.

A-222 Comparative Analysis of Clinical and Laboratory Parameters of Brazilian Patients with Severe Hipertriglyceridemia

Abstract Background The presence of elevated and sustained levels of triglycerides (TG) should raise the suspicion of primary causes of hypertriglyceridemia (HT), in which related genetic mutations would be identified. Thus, the aim of this study was to compare clinical and laboratory parameters of Brazilian patients with different etiologies of severe hypertriglyceridemia. Methods All patients with severe HT (considered as detection of TG above 880 mg/dL on at least 2 occasions) followed in the dyslipidemia outpatient clinic of Federal University of Ceará/Brazil, whose molecular study to investigate genetic variants potentially related to hypertriglyceridemia and pancreatitis has been previously performed (ABCA1 AGPAT2 AKT2 APOA5 APOC2 BSCL2 CAV1 CFTR CIDEC CTRC CYP27A1 GPIHBP1 LIPA LIPE LMF1 LMNA LMNB2 LPL PLIN1 POLD1 PPARG PRSS1 PSMB8 SMPD1 SPINK1 ZMPSTE24) were evaluated. Results Sixty-six patients were evaluated, identifying 39 (59%) with severe primary HT. Familial Chylomicronemia Syndrome (FCS) was identified in 14 (36%) of the 39 cases of severe primary HT. The main findings are shown in table 1. Compared with other etiologies, FCS patients presented an increased, precocious and recurrent incidence of pancreatitis, earlier detection and higher levels of TG. In patients with severe HT without identification of primary causes, a high incidence of alcoholism and diabetes was observed, with a tendency to higher glycated hemoglobin values among these, in addition to median Body Mass Index compatible with obesity. Conclusion FCS patients had the most severe clinical presentation of HT. The high prevalence of secondary factors for HT in patients with a negative genotype reinforces the indication of adequate management of these variables even in cases of primary etiology, aiming at not overlapping pathological mechanisms. In cases of severe HT, metabolic control is still a challenge.

Prevalence of Enteric Infections in Patients on Immune Checkpoint Inhibitors and Impact on Management and Outcomes.

Stool pathogen testing is recommended as part of the initial evaluation for patients with new-onset diarrhea on immune checkpoint inhibitors (ICIs), yet its significance has not been well-studied. We aimed to determine the impact of multiplex gastrointestinal (GI) pathogen PCR testing on the clinical course and use of immunosuppressive therapy in patients who develop diarrhea on ICIs. This retrospective cohort included individuals who underwent GI pathogen panel PCR for diarrhea on ICIs at Memorial Sloan Kettering between 7/2015 and 7/2021. The primary outcome was use of immunosuppressive therapy for suspected immunotherapy-related enterocolitis (irEC). Secondary outcomes included diarrhea severity and endoscopic and histologic disease patterns. Among 521 ICI-treated patients tested for GI pathogens, 61 (11.7%) had a positive PCR. Compared to patients without detectable infections, patients with infections had more frequent grades 3-4 diarrhea (37.7% vs. 19.6%, P < .01) and colitis (39.3% vs. 14.7%, P < .01). However, patients with infections did not have higher rates of persistent or recurrent diarrhea and were less likely to receive steroids (P < .01) and second-line immunosuppressive agents (P = .03). In 105 patients with lower endoscopy, similar trends were observed and no differences in endoscopic severity or histologic patterns were noted between groups. GI infections in ICI-treated patients presenting with diarrhea are linked to more severe but self-limited clinical presentations and may be optimally treated with observation and supportive care alone. Routine and timely stool pathogen testing may help avert unnecessary empiric immunosuppression for suspected irEC, which has been linked to blunted antitumor responses and numerous adverse effects.

SARS-CoV-2 vaccination in children and adolescents with and without type 1 diabetes mellitus.

Adults with Diabetes Mellitus (DM) have increased risk of severe clinical presentation during COVID-19 infection, while children and adolescents with type 1 diabetes (T1D) have the same mild clinical course as their healthy peers, especially those with optimal glycemic control. The present review focuses on the necessity of COVID-19 vaccination among children and adolescents with T1D, and also in their non-diabetic peers. The efficacy and safety of COVID-19 vaccines are also discussed, as well as their various side-effects, ranging from common mild to very rare and serious ones. Furthermore, the results of COVID-19 vaccination of adolescents with and without T1D are reported, as well as the efficacy and concerns about childhood vaccination. It is concluded that patients with DM of all age groups should maintain optimal diabetic control in order to avoid glycemic deterioration during COVID-19 infection. Furthermore, despite the very rare and serious complications of COVID-19 vaccines, vaccination against COVID-19 is recommended for children and adolescents with T1D to prevent glycemic deterioration and rare but serious complications of COVID-19 infection.

Patterns, Cost, and Immunological Response of MDR vs. Non MDR-Bacteremia: A Prospective Cohort Study.

Antimicrobial resistance (AMR) is a significant global health concern, posing a critical challenge for the effective management of infectious diseases. This study aimed to compare the immunological response, clinical outcomes, and associated costs in patients with bacteremia due to antibiotic-resistant vs. susceptible bacterial microorganisms. This study was a single-center, prospective cohort study conducted from May 2017 to November 2019. The study population consisted of patients admitted with a confirmed diagnosis of bacteremia. A total of 116 patients were included, with 53 (45.7%) harboring non-multidrug-resistant (non-MDR) bacterial isolates and 63 (54.3%) harboring multidrug-resistant (MDR) bacterial isolates. Patients with MDR bacteremia had more severe clinical presentations, as indicated by higher SOFA and APACHE II scores. Results revealed higher all-cause mortality rates (39.7% vs. 17%) and median healthcare costs (€4791 vs. €2843.5) in the MDR bacteremia group. Moreover, MDR bacteremia was linked to higher levels of TNF-a, indicating a differential immune response. Furthermore, MDR bacteremia was found to be an independent predictor of mortality (OR = 3.216, 95% CI: 1.338-7.730, p = 0.009) and increased healthcare costs (effect size of approximately 27.4%). These findings underscore the significant impact of antimicrobial resistance in healthcare settings, highlighting the urgency of addressing the challenges posed by MDR microorganisms.

Estimated plasma volume status in COVID-19 patients and its relation to comorbidities and clinical outcomes.

Blood plasma is a large reservoir of circulating mediators of inflammation and its expansion has been associated with unfavorable outcomes in patients with inflammatory and cardiovascular diseases. The aim of this study was to determine clinical and prognostic value of estimated plasma volume status (ePVS) in hospitalized patients with COVID-19. We retrospectively investigated 5871 consecutive COVID-19 patient hospitalized in our tertiary-level institution in period 3/2020-6/2021. ePVS was determined using the Strauss-derived Duarte formula and was correlated with clinical characteristics and unwanted outcomes. Median ePVS was 4.77dl/g with interquartile range 4.11-5.74. Higher ePVS was significantly associated with older age, female sex, higher comorbidity burden, worse functional status, less severe COVID-19 clinical presentation with lower severity and longer duration of symptoms, but more pronounced inflammatory profile with higher C-reactive protein, interleukin-6 and D-dimer levels (P < 0.05 for all analyses). In the multivariate regression analysis U shaped relationship of ePVS with mortality was revealed, present independently of age, sex, COVID-19 severity and comorbidity burden. In addition, higher ePVS was independently associated with higher tendency for mechanical ventilation, intensive care unit treatment, venous thromboembolism, major bleeding and bacteriemia and lower ePVS was independently associated with tendency for arterial thrombotic events. Higher ePVS, indicative of plasma volume expansion and inflammatory cytokine accumulation, may predispose respiratory deterioration and venous thromboembolism, despite less severe initial clinical presentation. Lower ePVS, indicative of hemoconcentration, may predispose arterial thrombotic events. Both may be associated with higher mortality in hospitalized COVID-19 patients.

Clinical Significance of Right Heart Thrombus With and Without an Associated Pulmonary Embolism

BackgroundRight heart thrombus is a rare but serious form of venous thromboembolic disease that may be associated with pulmonary embolism. The prognosis of patients with right heart thrombus presenting without a concomitant pulmonary embolism remains ill-defined. MethodsWe conducted a multi-center observational cohort study to compare patients presenting with right heart thrombus with and without a concurrent pulmonary embolism. The primary endpoint was 90-day all-cause mortality. Multivariable regression was utilized to assess primary and secondary outcomes. ResultsOf 231 patients with right heart thrombus, 104 (45.0%) had a pulmonary embolism at admission. The median age of the cohort was 59.4 years (interquartile range 44.9-71.3). Pulmonary embolism in the setting of a right heart thrombus was associated with an increased adjusted hazard of 90-day mortality (hazard ratio 3.68; 95% confidence interval [CI], 1.51-8.97). Additionally, these patients had a higher adjusted risk of in-hospital mortality (odds ratio [OR] 2.55; 95% CI, 1.15-5.94) and admission to the intensive care unit (OR 2.45; 95% CI, 1.23-4.94). Thrombus mobility (OR 2.99; 95% CI, 1.35-6.78) and larger thrombus sizes (OR 1.04; 95% CI, 1.00-1.07) were associated with development of concurrent pulmonary embolism. ConclusionsPatients with right heart thrombus and pulmonary embolism had a more severe clinical presentation, required more advanced therapies, and had reduced survival compared with those without a concomitant pulmonary embolism. Important variables associated with development of concomitant pulmonary embolism include thrombus mobility and size. Right heart thrombus in the setting of acute pulmonary embolism represents a unique clinical entity that is associated with worse prognosis compared with right heart thrombus only.

Assessing the evolution of SARS-CoV-2 lineages and the dynamic associations between nucleotide variations.

Despite seminal advances towards understanding the infection mechanism of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), it continues to cause significant morbidity and mortality worldwide. Though mass immunization programmes have been implemented in several countries, the viral transmission cycle has shown a continuous progression in the form of multiple waves. A constant change in the frequencies of dominant viral lineages, arising from the accumulation of nucleotide variations (NVs) through favourable selection, is understandably expected to be a major determinant of disease severity and possible vaccine escape. Indeed, worldwide efforts have been initiated to identify specific virus lineage(s) and/or NVs that may cause a severe clinical presentation or facilitate vaccination breakthrough. Since host genetics is expected to play a major role in shaping virus evolution, it is imperative to study the role of genome-wide SARS-CoV-2 NVs across various populations. In the current study, we analysed the whole genome sequence of 3543 SARS-CoV-2-infected samples obtained from the state of Telangana, India (including 210 from our previous study), collected over an extended period from April 2020 to October 2021. We present a unique perspective on the evolution of prevalent virus lineages and NVs during this period. We also highlight the presence of specific NVs likely to be associated favourably with samples classified as vaccination breakthroughs. Finally, we report genome-wide intra-host variations at novel genomic positions. The results presented here provide critical insights into virus evolution over an extended period and pave the way to rigorously investigate the role of specific NVs in vaccination breakthroughs.

Do magnetic resonance imaging features differ between persons with multiple sclerosis of various races and ethnicities?

Those of African American or Latin American descent have been demonstrated to have more severe clinical presentations of multiple sclerosis (MS) than non-Latin American White people with MS. Concurrently, radiological burden of disease on magnetic resonance imaging (MRI) in African Americans with MS has also been described as being more aggressive. Here, we review MRI studies in diverse racial and ethnic groups (adult and pediatric) investigating lesion burden, inflammation, neurodegeneration, and imaging response to disease modifying therapy. We also discuss why such disparities may exist beyond biology, and how future studies may provide greater insights into underlying differences.