Clinical Laboratory Evaluation Research Articles

Viewpoint: Provoked thrombosis in antiphospholipid syndrome.

Unprovoked thrombosis (thrombosis occurring without an established environmental factor favouring the episode) is a classic feature of APS. In the general population, provoked venous thromboembolism (VTE) is clearly defined and has clinical and therapeutic differences compared with unprovoked VTE. Whether provoked VTE in the context of APS may lead to a limited treatment duration is not well established. Therefore, careful clinical and laboratory evaluation is needed to identify patients eligible for a limited duration of anticoagulation treatment after provoked VTE. Given the uncertainties of available data, the risks and benefits of treatment decisions should be clearly explained. Decisions should be shared by both the patient and physician. Cardiovascular risk factors are common in patients with APS with arterial thrombosis. There are insufficient data suggesting that cardiovascular risk factor control would allow the cessation of anticoagulation. In most instances, arterial thrombosis will require prolonged anticoagulants. A careful analysis of clinical characteristics and laboratory evaluation, particularly the aPL antibody profile, is needed to make decisions on a case-by-case basis.

Synovial Fluid C-reactive Protein Clinical Decision Limit and Diagnostic Accuracy for Periprosthetic Joint Infection.

Introduction C-reactive protein (CRP) has long served as a prototypical biomarker for periprosthetic joint infection (PJI). Recently, synovial fluid (SF)-CRP has garnered interest as a diagnostic tool, with several studies demonstrating its diagnostic superiority over serum CRP for the diagnosis of PJI. Although previous studies have identified diagnostic thresholds for SF-CRP, they have been limited in scope and employed various CRP assays without formal validation for PJI diagnosis. This study aimed to conduct a formal single clinical laboratory validation to determine the optimal clinical decision limit of SF-CRP for the diagnosis of PJI. Methods A retrospective analysis of prospectively collected data was performed using receiver operating characteristic (ROC) and area under the curve (AUC) analyses. Synovial fluid samples from hip and knee arthroplasties, received from over 2,600 institutions,underwent clinical testing for PJI at a single clinical laboratory (CD Laboratories, Zimmer Biomet, Towson, MD) between 2017 and 2022. Samples were assayed for SF-CRP, alpha-defensin, white blood cell count, neutrophil percentage, and microbiological culture. After applying selection criteria, the samples were classified with the 2018 ICM PJI scoring system as "infected," "not infected," or "inconclusive." Data were divided into training and validation sets. The Youden Index was employed to optimize the clinical decision limit. Results A total of 96,061 samples formed the training (n = 67,242) and validation (n = 28,819) datasets. Analysis of the biomarker median values, culture positivity, anatomic distribution, and days from aspiration to testing revealed nearly identical specimen characteristics in both the training set and validation set. SF-CRP demonstrated an AUC of 0.929 (95% confidence interval (CI): 0.926-0.932) in the training set, with an optimal SF-CRP clinical decision limit for PJI diagnosis of 4.45 mg/L. Applying this cutoff to the validation dataset yielded a sensitivity of 86.1% (95% CI: 85.0-87.1%) and specificity of 87.1% (95% CI: 86.7-87.5%). No statistically significant difference in diagnostic performance was observed between the validation and training sets. Conclusion This study represents the largest single clinical laboratory evaluation of an SF-CRP assay for PJI diagnosis. The optimal CRP cutoff (4.45 mg/L) for PJI, which yielded a sensitivity of 86.1% and a specificity of 87.1%, is specific to the assay methodology and laboratory performing the assay. We propose that an SF-CRP test with a laboratory-validated optimal clinical decision limit for PJI may be preferable, in a clinical diagnostic setting, to serum CRP tests that do not have laboratory-validated clinical decision limits for PJI.

New Developments in the Ultrasonography Diagnosis of Gallbladder Diseases

Gallbladder diseases are very common, and their diagnosis is based on clinical–laboratory evaluation and imaging techniques. Considering the different imaging diagnostic tools, ultrasound (US) has the advantage of high accuracy combined with easy availability. Therefore, when a gallbladder disease is suspected, US can readily assist the clinician in the medical office or the emergency department. The high performance of US in the diagnosis of gallbladder diseases is mainly related to its anatomic location. The most frequent gallbladder pathological condition is gallstones disease, easily diagnosed via US examination. Acute cholecystitis (AC), a possible complication of gallstone disease, can be readily recognized due to its specific sonographic features. Additionally, a number of benign, borderline or malignant gallbladder lesions may be detected via US evaluation. The combined use of standard B-mode US and additional sonographic techniques, such as contrast-enhanced ultrasonography (CEUS), may provide a more detailed study of gallbladder lesions. Multiparametric US (combination of multiple sonographic tools) can improve the diagnostic yield during gallbladder examination.

Identifying Novel Coagulation Biomarkers for Thrombosis in Patients with Lymphoma

CONCLUSION Thromboembolic events are a common complication of lymphoma, influenced by a number of factors, including status of the disease, patient characteristics and treatment modalities. Recent studies demonstrated presence of hemostatic dysregulation in lymphoma patients with the possible involvement of tissue factor (TF) in the development of thrombotic events; however, more data are needed to link coagulation biomarkers' levels with clinical data and increased thrombotic risk. TF initiates blood coagulation and expressed by nonvascular cells plays a major role in hemostasis, while TF expressed by vascular cells induces intravascular thrombosis. In this study, we aimed to profile coagulation biomarkers and determine the roles of neutrophils, monocytes, platelets and endothelial cells and their interactions in thrombus formation in patients with lymphoma. Patients with newly diagnosed lymphoma were prospectively recruited and followed for all thromboembolic events from the time of diagnosis until 3 months after the last cycle of therapy. Peripheral blood samples were obtained before hematological treatment initiation from 127 patients with lymphoma. The coagulation factors profile (Fibrinogen, P-selectin, FVIII, Thrombin and TF) was measured by enzyme-linked immunosorbent assay (ELISA), while TF expression and monocyte-platelet aggregates were determined by flow cytometry. The isolation, quantification and flow cytometry profiling of extracellular vesicles (EVs) ≤1.0 µm have been done according to the protocol developed by Institute for Medical Research, Belgrade, Serbia. Thromboembolic events were diagnosed objectively based on clinical examination, radiographic studies and laboratory evaluation. The mean patients' age was 55±16 years (range, 18-86 years); 44.9% were males. Most patients (58.2%) had advanced stage disease (III/IV), and 35.4% had ECOG performance status ≥1. More than half of the patients had aggressive forms of lymphoma (64.6%), mostly diffuse large B-cell lymphoma (DLBCL). Thrombosis occurred in 14.3% of patients with lymphoma (18/127), predominantly in patients with aggressive (18.3%) vs. indolent forms (6.8%). Total number of thrombosis was 22 (4 patients had more than one thrombosis site), and venous thrombosis was the most prevalent (72.7%). ThroLy score ≥2 had 72.2% of patients with thrombosis, in contrast to 37% of patients without thrombosis. The median value of TF was higher in patients with thrombosis compared to those without thrombosis (224.41 [93.1-446.0] (median [IQR]) vs. 136.43 [109.4-193.4], p=0.036). The concentration of the other assessed coagulation related cells and biomarkers were not significantly different between patients who developed thrombosis during follow-up and those who did not. In multivariate regression analysis, ThroLy score ≥2 (OR=5.505, 95%CI 1.505‒20.100, p=0.01), TF (OR=1.005, 95%CI 1.002‒1.009, p=0.003), and aggressive form of lymphoma (OR=4.680, 95%CI 1.132‒19.356, p=0.033), were independent prognostic factors for thrombosis occurrence. CD11b +CD16 + neutrophils were increased 8-fold in aggressive (DLBCL) compared to indolent form of lymphoma (p<0.001), as were 2-fold CD61 + platelets and 3-fold CD31 + endothelial cells labelled with TF (CD142 +, p<0.05) procoagulant EVs. The monocyte-platelet aggregates (CD14 +CD45 +CD41 +) were increased 5-fold in DLBCL patients compared to the healthy controls (p<0.001). The presented results support the use of ThroLy score for differentiating the sub-groups of lymphoma patients who are at increased risk for thrombotic events, while profiling coagulation biomarkers in different lymphoma populations may aid in understanding the pathophysiologic mechanisms underlying the thromboembolic events. Special emphasis should be placed on the assessment of TF which might be used as a coagulation biomarker in addition to clinical prediction scores.

Non-O Blood Group and Pretreatment Risk of Venous Thromboembolism in Patients with Diffuse Large B-Cell Lymphoma

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most frequent aggressive non-Hodgkin lymphoma (NHL). It has been extensively documented that the risk of venous thromboembolism (VTE) is augmented in patients with aggressive lymphomas. The timing of VTE occurrence in this group of patients is highly variable and depends on diverse risk factors. Lately, it has been observed that ABO blood group type can have a prognostic impact on both thrombosis development and survival outcomes in patients with cancer. Therefore, the study aimed to examine the ABO blood group as a risk factor for VTE development in patients with DLBCL, to examine the relation between ABO blood groups and the timing of VTE development, and to investigate the association between ABO group type and treatment and survival outcomes. Methods: A total of 340 patients with DLBCL (newly diagnosed and relapsed) have been included in the study and all of them have been treated at the Lymphoma Center, Clinic for Hematology, University Clinical Center of Serbia. Data regarding VTE events were collected for all the patients included in the study, from the time of diagnosis to 3 months after the last cycle of therapy. ABO blood group has been determined before the treatment initialization. VTE was diagnosed objectively based on clinical examination, laboratory evaluation, and radiographic studies. Results: The median patients' age was 60 years (range, 19-89 years) and 52.9% were males. Newly diagnosed patients were dominant in the study population (94.4%). The majority of patients had advanced stage (stage III Ann Arbor 22.3% and stage IV 30.7%, respectively) of the disease. The median international prognostic index (IPI) was 2 (range, 0-5). Complete remission (CR) and partial remission (PR) were most commonly recorded (51.7% and 28.8%, respectively). The rate of VTE was 12.6% (43 patients), with the highest frequency of lower and upper extremity deep vein thrombosis (12 patients each). VTE was diagnosed before the initiation of specific hematological treatment in 54.5% of DLBCL patients, whilst 45.5% of DLBCL patients have been diagnosed with VTE following the hematological treatment initiation. The following distribution of ABO blood groups among DLBCL patients was detected: A blood group 39.4%, B blood group 17.6%, AB blood group 9.1%, and O blood group 33.8%. No significant association between VTE development and ABO group type was found (p=0.706) nor between VTE development and time of VTE development (p=0.895). The rate of VTE in DLBCL patients with A blood type was 4.7%, in B 2.1%, in AB 1.8%, and in O 4.1%, respectively (p=0.706). DLBCL patients with the non-O blood group developed VTE significantly more frequently prior to the hematological treatment commencement than after the treatment initiation (6.2% vs. 2.6%, p=0.003). Univariate logistic regression analysis showed that non-O blood type in DLBCL patients is a prognostic factor for VTE development prior to hematological treatment initiation (odds ratio (OR)=8.56, 95% confidence interval (CI): 1.92-38.21, p=0.005). Multivariate logistic regression model demonstrated that non-O blood type is an independent predictor of pretreatment VTE development in DLBCL patients (OR=18.33, 95% CI: 1.51-222.87, p=0.022). Therapy response of DLBCL patients was significantly associated with the ABO blood group (p=0.012) in the way that A and AB blood types were associated with unsatisfactory treatment response (no statistically significant association was found between ABO blood type and DLBCL patients' Ann Arbor stage, mediastinal involvement, bulky disease, extranodal disease, IPI, central nervous system involvement). Univariate regression analysis showed that A blood type is a predictor of unsatisfactory therapy response in patients with DLBCL (OR=1.85, 95% CI: 1.04-3.29, p=0.035). However, in multivariate regression model, this finding lost statistical significance. No significant association was observed regarding ABO blood type, progression-free survival, and overall survival in patients with DLBCL (p=0.398 and p=0.593, respectively). Conclusion: In DLBCL patients, non-O blood group is an independent predictor of VTE occurrence prior to initiation of a specific hematologic treatment. DLBCL patients with A blood group could be at risk of insufficient treatment response.

The role of adiposity, adipokines and polymorphisms of leptin and adiponectin in myelodysplastic syndromes.

The aim of the present study was to investigate the relationship between leptin and adiponectin gene polymorphisms, circulating levels of leptin and adiponectin, adiposity and clinical markers in patients with myelodysplastic syndrome (MDS). This cross-sectional study was conducted with 102 adults and elderly MDS patients and 102 age- and sex-matched controls. Clinical characteristics, co-morbidities, anthropometric data, laboratory evaluation and genetic analysis (polymorphisms -2548G > A/rs7799039 of the LEP gene and +276G > T/rs1501299 of the ADIPOQ gene) were investigated. Serum leptin was higher and adiponectin lower in MDS when compared with controls. There was a significant positive correlation between serum leptin levels and BMI (r = 0·264, P = 0·025), waist circumference (r = 0·235, P = 0·047), body fat percentage (BF %) (r = 0·373, P = 0·001) and the fat mass index (FMI) (r = 0·371, P < 0·001). A lower mean adiponectin was found among patients with high BF %, higher visceral adiposity index and metabolic syndrome. A significant association was found between the AA genotype (mutant) of the LEP polymorphism rs7799039 and male sex and blast excess (≥ 5 %). In addition, a significant association was observed between the TT genotype (mutant) of the ADIPOQ rs1501299 polymorphism and Fe overload. These results demonstrate the importance of a comprehensive and systematic evaluation in patients with MDS in order to identify and control negative factors not related to the disease at an early stage.

Effect of improved nursing strategy on prognosis of older immunosuppressed patients with pneumonia and sepsis

To investigate the effect of improved nursing strategy on prognosis of older immunosuppressed patients with pneumonia and sepsis. A prospective study was conducted. The older immunosuppressed patients with pneumonia and sepsis admitted to the department of intensive care medicine and emergency intensive care unit (ICU) of Peking Union Medical College Hospital from January 2017 to July 2022 were enrolled. In the first stage (from January 2017 to December 2019), patients received the original nursing strategy (original nursing strategy group), including: (1) nurses were randomly assigned; (2) routine terminal cleaning; (3) ICU environmental cleaning twice a day; (4) oral care was performed with chlorhexidine twice a day; (5) original lung physiotherapy [head of bed elevated at 30 degree angle-45 degree angle, maintaining a Richmond agitation-sedation scale (RASS) -2 to 1, sputum aspiration as needed]. After 1 month of learning and training of the modified nursing treatment strategy for nurses and related medical staff, the patients in the second stage (from February 2020 to July 2022) received the improved nursing strategy (improved nursing strategy group). The improved nursing strategy improved the hospital infection prevention and control strategy and lung physical therapy strategy on the basis of the original nursing strategy, including: (1) nurses were fixed assigned; (2) patients were placed in a private room; (3) enhanced terminal cleaning; (4) ICU environmental cleaning four times a day; (5) education and training in hand hygiene among health care workers was improved; (6) bathing with 2% chlorhexidinegluconate was performed once daily; (7) oral care with a combination of chlorhexidine and colistin was provided every 6 hours; (8) surveillance of colonization was conducted; (9) improved lung physiotherapy (on the basis of the original lung physiotherapy, delirium score was assessed to guide early mobilization of the patients; airway drainage was enhanced, the degree of airway humidification was adjusted according to the sputum properties, achieving sputum viscosity grade II; lung ultrasound was also used for lung assessment, and patients with atelectasis were placed in high lateral position and received the lung recruitment maneuver). Baseline patient information were collected, including gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, pathogens and drug therapy. The primary outcome was 28-day mortality, and the secondary outcomes were duration of mechanical ventilation, length of ICU stay, and ICU mortality. Multivariate Logistic regression analysis was used to determine the risk factors for 28-day death in older immunosuppressed patients with pneumonia and sepsis. Finally, 550 patients were enrolled, including 199 patients in the original nursing strategy group and 351 patients in the improved nursing strategy group. No significant differences were found in gender, age, underlying diseases, source of admission, disease severity scores, vital signs, ventilatory parameters, blood gas analysis, life-sustaining treatments, clinical laboratory evaluation, indicators of infection and inflammation, coexisting pathogens or drug therapy between the two groups. Compared with patients in the original nursing strategy group, those in the improved nursing strategy group had significantly fewer duration of mechanical ventilation and length of ICU stay [duration of mechanical ventilation (days): 5 (4, 7) vs. 5 (4, 9), length of ICU stay (days): 11 (6, 17) vs. 12 (6, 23), both P < 0.01], and lower ICU mortality and 28-day mortality [ICU mortality: 23.9% (84/351) vs. 32.7% (65/199), 28-day mortality: 23.1% (81/351) vs. 33.7% (67/199), both P < 0.05]. Multivariate Logistic regression analysis showed that the improved nursing strategy acted as an independent protective factor in 28-day death of older immunosuppressed patients with pneumonia and sepsis [odds ratio (OR) = 0.543, 95% confidence interval (95%CI) was 0.334-0.885, P = 0.014]. Improved nursing strategy shortened the duration of mechanical ventilation and the length of ICU stay, and decreased ICU mortality and 28-day mortality in older immunosuppressed patients with pneumonia and sepsis, significantly improving the short-term prognosis of such patients.

Radiological Evidence of Testicular Damage in Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Sonoelastography's Potential Role.

This preliminary study aimed to evaluate the possible damage to the male reproductive system that the severe acute respiratory syndrome coronavirus 2 virus causes by quantitatively measuring and comparing the tissue stiffness of the testis and epididymis with acoustic radiation force impulse sonoelastography in patients who have COVID-19 with a healthy control group. This prospective study was conducted between February and July 2021 with 65 cases. We used sonoelastography to evaluate male patients 18 years or older, who had applied to the urology clinic with nontesticular complaints, and were found to not have any underlying testicular pathology after a clinical-laboratory evaluation. The clinical-laboratory imaging findings and reverse transcription-polymerase chain reaction test results of all patients diagnosed with COVID-19 were reviewed from the hospital database. We measured the shear wave velocity values of the epididymis and the testes of 31 proven severe acute respiratory syndrome coronavirus 2 patients and 34 healthy subjects and compared them with an independent t test. For the patient and control group subjects, the mean age was 37.55 ± 13.08 (23-71) and 40.5 ± 16.25 (18-81) years, respectively. The mean shear wave velocity values of the left-right and bilateral testes and epididymis of the patient group were statistically substantially higher (P ˂ 0.05) than in the control group. In the receiver operating characteristic analysis, when the cutoff values for the bilateral testes and epididymis were determined as 1.39 and 1.64 m/s, respectively, the AUC was 77% to 73.4%, the sensitivity was 87% to 74%, and the specificity was 65% to 62%. Our findings show that testicular and epididymal tissue stiffness increased in patients with COVID-19. We recommend adding sonoelastography to urogenital examinations of male reproductive system in patients who are recovering from COVID-19.

Sheehan's Syndrome in India: Clinical Characteristics and Laboratory Evaluation.

Sheehan's Syndrome (SS) is an important cause of hypopituitarism especially in developing countries though it remains underdiagnosed to a great extent. Torrential bleeding after delivery followed by lactation failure and amenorrhoea gives a clue to the diagnosis which is usually made after several years of delivery. It was a retrospective observational study conducted by reviewing the case records of 38 cases of SS. The age, anthropometric measurements, signs and symptoms, biochemical parameters, hormone levels and imaging reports were examined and analyzed. The mean age at presentation was 36.5years because there was a delay of 8.4years from last delivery before diagnosis could be made. Ninety percent patients presented with lactation failure. Anaemia, hypotension, hypogonadism, hypothyroidism, and altered lipid profile were the most common findings. The mean systolic blood pressure (BP) was 80.95mm and diastolic BP was 51.6mm of Hg at the time of presentation. Hyponatremia was the most common electrolyte abnormality noted and low HDL was the commonest lipid abnormality. A large percentage of patients presented with amenorrhea, lactation failure, and decreased or absent axillary/pubic hair. Shock, anemia, and hyponatremia were also common symptoms among the patients studied. The diagnosis of SS rests upon a thorough history taking of the postpartum events in cases presenting with hypopituitarism irrespective of the age at presentation. Proper antenatal care with exclusive institutional deliveries can reduce the prevalence of SS in developing countries.

Recommendations for diagnosis and treatment of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with complicated pathogenesis and diverse clinical manifestations. The current recommendations of the Chinese Rheumatology Association are based on a comprehensive investigation of evidence based medicine, domestic and international guidelines for SLE, and experts' proposals, and aim to provide a more scientific and authoritative reference for the diagnosis and management of SLE. The recommendations focus on four aspects; clinical manifestations, laboratory evaluation, diagnosis and disease assessment, and disease treatment and monitoring. The goal of the recommendations is to standardize the diagnosis and treatment of SLE in China so as to improve the prognosis of SLE patients.

#6830 APPLICATION OF THE NEURAL NETWORK ALGORITHM IN THE ASSESSMENT OF THE STAGE OF ACUTE KIDNEY DAMAGE AND THE SELECTION OF TREATMENT

Abstract Background and Aims Acute kidney injury is a syndrome that occurs in different clinical situations, under the influence of different risk factors, in patients of all ages, especially those in the intensive care unit. The problem of acute kidney damage refers to numerous clinical situations, different disease mechanisms and poor outcomes. In addition, with the current definition of acute kidney injury, only one conventional marker is available for diagnosis in daily clinical practice. To recognize the disease promptly and start treatment, and thereby improving the outcome, the paper presents a model for recognizing acute kidney damage in the stage that requires hemodialysis treatment. Method The study included 86 hospitalized patients with acute renal impairment who were divided according to the stage of renal impairment at admission to hospital treatment into three groups. The assessment of acute renal impairment and the classification of disease stages were based on the diagnostic stages by the K / DIGO group. All examined patients were over 18 years of age. In the first stage of the disease it was 12.79%, in the second stage it was 15.12%, and in the third 72.09% of patients. Test methods included clinical processing, laboratory evaluation, functional tests, and echosonographic examination. Clinical data included demographic, comorbidity and vital parameters, baseline full blood count, biochemistry and renal function tests. Further laboratory investigations were performed as indicated clinically thereafter. Spot blood and urine samples were collected from all patients in the morning after overnight fasting. The neural network was created in feed forward back propagation of the connection between the data of 69 patients with 31 parameters. In pattern recognition, the neural network learns to recognize the conditions in which it was decided to send the patient to dialysis 10 or to send to classical treatment 01. The training function analyzed the patients separated in three special categories 80% training, 10% test and 10% validation. The algorithm of the learning function is a scaling gradient that adapts the input data to the output data. Results The neural network achieved a performance of 0.14322 in 6 epochs. In a test with the data of 17 patients, it was shown that the neural network indicates for which patients dialysis treatment is a better option that fits with AKI stage 3. For patients with the first and second stages of the disease, conservative treatment is a better therapeutic choice. Conclusion This paper deals with a current topic by analyzing data using a neural network algorithm to help assess the stage of the disease in high-risk hospitalized patients with acute kidney injury and select treatment modalities. The conclusions derived from this analysis should help with stage recognition and the selection of treatment modalities for patients with acute kidney injury.

ST-elevation myocardial infarction, severe cardiogenic shock, and myocarditis secondary to leptospirosis: A rare case report

Background: Leptospirosis is a bacterial infection that can lead to several organ dysfunctions. However, cardiac involvements in leptospirosis are uncommon findings. The unknown pathogenesis and association between leptospirosis and cardiac involvements can lead to a diagnostic challenge and case rarity. This study aims to report a diagnosis challenge through physical and laboratory examination of a patient with ST-elevation myocardial infarction (STEMI) and myocarditis without common leptospiral-associated organ dysfunction features. We also report the therapeutic strategies in this case, despite its clinical guideline limitation. Case: A 35-year-old male patient came to the emergency department with flu-like symptoms. Twenty-four hours later, the patient showed acute angina, STEMI, and elevated high-sensitivity cardiac troponin followed by cardiogenic shock without significant modifiable and non-modifiable risk factors for heart diseases. The patient received fibrinolytic, supportive therapy and correction of hemodynamic derangement. We found thrombocytopenia on the second day. Surprisingly, the immunoserology showed positive anti-leptospira IgM and negative anti-dengue IgM and IgG. Further, there was echocardiography suspected myocarditis due to high echogenicity in the left ventricle's basal-apical lateral endocardium. Thus, we diagnosed this case as leptospirosis with cardiac involvement. Direct cardiac tissue damage due to systemic vasculitis, disseminated intravascular coagulation, and pro-inflammatory cytokine storm is believed to be pathomechanism in leptospirosis with cardiac involvement. After diagnosis establishment, his final therapies in the hospital were Aspirin, Atorvastatin, Clopidogrel, Spironolactone, Ramipril, Carvedilol, Omeprazole, Doxycycline, and Ceftriaxone. Subsequently, he was discharged from hospital and continued to receive cardiovascular medications, antibiotics, antiplatelet, potassium-sparing diuretics, and omeprazole. Conclusion: This case highlights the importance of thorough clinical-laboratory evaluation in a patient with an atypical leptospiral presentation. Although leptospirosis is not a common cause of heart diseases such as STEMI, cardiogenic shock, and myocarditis, we recommend supportive therapy and correction of hemodynamic derangement for leptospirosis with cardiac involvement, in addition to leptospiral antibiotic drug itself.

Historical Cohort of Severe Congenital Neutropenia in Iran: Clinical Course, Laboratory Evaluation, Treatment, and Survival.

Severe congenital neutropenia (SCN) is one of the primary immunodeficiency diseases developed by genetic alterations. Mutations in several genes including HAX-1 , G6PC3 , jagunal , and VPS45 account for autosomal recessive SCN. Patients with SCN registered in the Iranian Primary Immunodeficiency Registry and referred to our clinic at the Children's Medical Center were reviewed. Thirty-seven eligible patients with a mean age of 28.51 ± 24.38 months at the time of diagnosis were included. Nineteen cases had consanguineous parents and 10 cases had confirmed or unconfirmed positive family history. The most prevalent infectious symptoms were oral infections followed by respiratory infections. We identified HAX-1 mutation in 4, ELANE mutation in 4 cases, G6PC3 mutation in 1, and WHIM syndrome in 1 case. Other patients remained genetically unclassified. After the median follow-up of 36 months from the time of diagnosis, the overall survival was 88.88%. The mean event-free survival was 185.84 months (95% CI: 161.02, 210.66). Autosomal recessive SCN is more common in countries with high rates of consanguinity like Iran. The genetic classification was possible only for a few patients in our study. This might suggest that there are other autosomal recessive genes causative of neutropenia that have yet to be described.

Takayasu arteritis associated with autoimmune/inflammatory syndrome induced by adjuvants: a case-based review.

Takayasu's arteritis (TA) is a chronic granulomatous vasculitis that predominantly affects the aorta and its major branches. Despite advancements in the understanding of the pathogenic pathways of vascular inflammation, the etiology and predisposing factors of TA remain to be fully understood. In susceptible individuals, exposure to adjuvants may trigger, unlock or unmask an autoimmune disorder, presenting as non-specific constitutional symptoms or a fully developed autoimmune syndrome such as vasculitis. Here, we hypothesize that TA could be triggered by siliconosis, a subtype of the autoimmune/inflammatory syndrome induced by adjuvants (ASIA). ASIA, also known as Shoenfeld syndrome, encompasses a wide range of autoimmune and immune-mediated diseases resulting from dysregulation of the immune response after exposure to agents with adjuvant activity. This case report describes the development of large artery vasculitis, TA, in an individual one year following the placement of silicone breast implants. The patient initially presented with non-specific symptoms, and multiple imaging methods were employed, including ultrasound diagnostics, CT angiography, and 18-fluorodeoxyglucose positron emission tomography/CT. These techniques revealed vasculitic alterations in the carotid arteries and thoracic aorta. Initial treatment with glucocorticosteroids proved ineffective, prompting the addition of steroid-sparing immunosuppressive agents. Due to the distinct clinical symptoms, disease progression, implant-associated fibrosis, and resistance to therapy, the potential involvement of implants in the development of large-vessel vasculitis was considered, and a potential association with ASIA was postulated. Although there is limited evidence to support a direct link between adjuvants and the pathogenesis of TA, similarities in cellular immunity between the two conditions exist. The diagnosis of this complex and potentially debilitating condition requires a comprehensive clinical examination, laboratory evaluation, and instrumental assessment. This will aid in identifying potential contributing factors and ensuring successful treatment.

Determination of Factor II Codons Genotype in Southeastern Iranian Patients With Hereditary Deficiency of Factor II

Objectives: Congenital prothrombin (factor II) deficiency is an inherited rare bleeding disorder with an autosomal recessive manner. The prevalence of this disorder is about one in 2000000 people in general population, but it is more common in areas with a high rate of consanguinity. To date, there is no report on the absence of prothrombin, which is a life-threating disorder. Considering the importance of factor II in body homeostasis, this study aimed to find any possible mutation of coagulation factor II codons in patients with inherited factor II deficiency in southeastern Iran. Materials andMethods: This study was conducted on 12 patients with inherited deficiency of prothrombin. Early diagnosis was based on clinical symptoms, laboratory evaluation, and family history. Then, the function level of prothrombin was measured, the initial diagnosis of disease was confirmed, and polymerase chain reaction (PCR) analysis was performed. Finally, gene sequencing and genotyping of factor II was done. Results: Molecular analysis indicated a point mutation in exon 7 in three patients and a frameshift mutation in exon 14 due to addition of a thymine base at position 1760-1761 in one patient, both of which have been reported for the first time. Conclusions: Molecular methods performed on patients from Southeastern Iranian population in terms of coagulation factor II deficiency revealed a substitution mutation in exon 7 in three patients and a frameshift mutation in exon 14 in one patient, both of which were reported for the first time. Considering the significant difference between the clinical symptoms of the present study and previous studies, probably the type of mutations reported in this study (for the first time) caused these clinical symptoms, but statistical studies did not show any relationship between the type of mutation and the occurrence of clinical symptoms. And it needs more investigations on more patients, with a larger population.

THE ANALYTICAL STUDY OF “ROLE OF VARIOUS ETIOLOGICAL FACTORS FOR THE PRECIPITATION OF ACUTE SEIZURES

Background: Seizures are a result of shift in the normal balance of excitation and inhibition within the central nervous system. Acute symptomatic seizures are those caused or provoked by acute medical or neurological illness Aims And Objectives: 1.To study the etiological spectrum of acute symptomatic seizures. 2. To evaluate new onset seizures by clinical and appropriate laboratory and radiological evaluation Methods: 170 patients attending the outpatient department and emergency department with diagnosis of acute seizures in Department of Medicine and allied specialties in KIMS &amp;RF hospital from SEPTEMBER 2020 to OCTOBER 2022 are selected for the study Results: In this study ASS was seen more in males (60%) than females (40%).GTCS was seen in 75.2% subjects, 21.1% subjects presented with focal seizures and 3.52% subjects had focal seizures with secondary generalisation. Metabolic insults were found in 25.9% subjects ,Vascular insults 15.9% , Drug withdrawal seizures 15.9%, adult onset seizures 5%, Primary generalized epilepsy 8.8%, Cerebral Venous Sinus thrombosis 7.6%, Alcohol withdrawal in 4.1%,trauma 5.3%, neurocysticercosis 2.4%,tuberculoma 2.9%,drug poisoning 1.2% Conclusion: Incidence of ASS was more during early adulthood and middle aged persons. Metabolic insults accounted for a large portion (25.9%) ,vascular insults (15.9%), drug withdrawal seizures(15.9%), seizures secondary to CVT (7.6%), trauma(5.3%), alcohol withdrawal(4.1%), NCC (2.4%), tuberculoma (2.9%).Acute symptomatic seizures continue to be a useful concept for classication and prognosis

BRADYCARDIA-AN ALARMING SIGN IN DENGUE FEVER

Dengue Fever is one of the most common vector borne disease which is caused by bite of Aedes aegypti in Tropical parts of world. Bleeding manifestations are most common signs due to Thrombocytopenia. Relative Bradycardia which is becoming one of the cause of mortality in Dengue Fever. This study aims to observe, changes in Heart rate in Dengue Fever. Materials and methods: This was an observational study done at Narayana medical college and hospital, Nellore, from June 2021 to October 2022 on 150 patients satisfying inclusion and exclusion criteria, demographic data and clinical features and laboratory evaluation was done for patients in the study vitals signs (pulse/heart rate, Blood pressure, respiratory rate, temperature) was noted for all patients. Results: Out of 150 patients, 43.3% have relative bradycardia and 30% patients have absolute bradycardia with ECG showing sinus bradycardia in 28% of patients. Conclusion: Relative bradycardia in dengue fever patients is present in association with thrombocytopenia and is important contributing factor to mortality in patients with dengue fever.

Quantification of Neutrophil Extracellular Traps (NETs) in Pediatric Patients with COVID-19 and Multisystem Inflammatory Syndrome (MIS-C) through Plasma and Peripheral Smear Analysis

Background: In response to inflammation, neutrophils expel NETs, decondensed chromatin coated with histones and granular proteins that capture pathogens. NET degradation products (NDPs), including cell free (cf) DNA, citrullinated histone 3 (citH3), and myeloperoxidase (MPO), are elevated in adults with COVID-19 and contribute to endothelial injury. However, NETs have not yet been quantified in pediatric patients with active SARS-CoV-2 infection, or children who develop the post-infection inflammatory syndrome MIS-C. Although NDPs can be measured in plasma samples in the research setting, it has been proposed that smudge cells (SC), leukocyte remnants composed of extracellular chromatin that are identified by automated digital morphology systems, represent circulating NETs. Automated quantification of SCs is attractive strategy to quantify systemic NET load because it is routinely performed on patient samples as part of a standardized clinical laboratory evaluation. Aims: The aims of this study are to measure NETs in the plasma of children with COVID-19 or MIS-C, and to determine if NDP and SC% elevation correlate with NET levels Methods: We analyzed plasma samples obtained from patients admitted to The Children's Hospital of Philadelphia (CHOP) with COVID-19 between April and October 2020, including children with mild (N=21) or severe (N=13) COVID-19, and MIS-C (N=23). Remnant plasma from healthy patients (N=13) was used as a control. Samples were analyzed with the Olink Explore 1536/384 protein biomarker platform, cfDNA was meauasred with a fluorescent plate assay, and citH3 was quantified wit a commercial ELISA (Cayman). Spearman rank correlation was used to quantify the association between cfDNA and citH3, protein biomarkers, and clinical data. We next reviewed 56 peripheral smears from patients with mild COVID-19(N=5), severe COVID-19 (N=8), and MIS-C (N=6), using the Cellavision® hematology autoanalyzer. Results were validated independently by two blinded observers, and Spearman rank correlation was used to measure the association between SC%, leukocyte counts, and clinical laboratory data. Results: cfDNA and citH3 were significantly elevated in pediatric patients with COVID-19 compared to healthy controls, with the highest levels observed in patients with severe COVID-19 and MIS-C (Figure 1). Correlative analysis with results of proteomic studies showed that citH3 was significantly associated with multiple markers of neutrophil activation including MPO, matrix metalloproteinase-9, and IL-8, demonstrating that citH3 is a specific marker of NET release. Although cfDNA does not exclusively originate from NETs, it was significantly correlated with the specific NET marker citH3 (r=0.7844, p<0.0001), suggesting that cfDNA is in part derived from NETs. Analysis of clinical data showed that citH3 was inversely correlated with sodium (r=-0.4289, p=0.011) and positive correlated with troponin levels (r=0.3587, p=0.0438). cfDNA significantly correlated with the complement membrane attack complex (r=0.2986, p=0.024) and LDH (r=0.5463, p=0.0015). Review of peripheral smears showed SC levels were elevated in pediatric patients with COVID-19 (Figure 2). SC% positively correlated with monocytes (r=0.4047, p=0.0018) and eosinophils (r=0.3420, p=0.0092) and inversely correlated with neutrophil counts (r=-0.4064, p=0.0017), suggesting that many SC originate from neutrophils. SC% was also inversely correlated with activated partial thromboplastin time (aPTT,r=-0.5153, p=0.04), a finding that may indicate activation of the contact coagulation pathway by increased plasma NETs. Conclusion: Plasma NET markers are elevated in the plasma of pediatric patients with COVID-19, with the highest levels observed in those with severe disease and MIS-C. Correlation of cfDNA and citH3 with proteins associated with neutrophil activation, complement fixation, and organ dysfunction adds support to our hypothesis that these markers originate from NETs and contribute to endothelial injury. SC% is elevated in children with COVID-19 infection and MIS-C. Further studies are underway to determine whether SCs originate from NETs. This work suggests there may be clinical utility in quantifying and reporting SC% in the hematology laboratory to identify increased NETs in children, a finding relevant to the study and treatment of COVID-19 and other viral infections. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

WITHDRAWN

SESSION TITLE: Systemic Diseases Causing Pulmonary Havoc SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) is an immune-mediated disease characterized by necrotizing vasculitis of the small blood vessels. Pulmonary involvement is common in AAV. Nodules and pleural effusions are the most common pulmonary finding in AAV. Fibrosing interstitial lung disease (ILD) is rarely associated with AAV, and it has a significant prognostication impact. We present a case of usual interstitial pneumonia (UIP) found in a patient with anti-Myloperoxidase (MPO) ANCA and rapidly progressive disease. CASE PRESENTATION: A 71-year-old female presented to the hospital with progressive exertional dyspnea and weakness for several months. Her physical exam was remarkable for bilateral basilar crackles. Oxygen saturation was 91% on ambient air. Chest radiograph showed lower zones interstitial infiltrates. Computed tomography of the chest showed diffuse reticular opacities in both lungs with honeycombing and traction bronchiectasis consistent with definite usual interstitial pneumonia (UIP) pattern. Laboratory evaluation revealed elevated serum creatinine (5.73 mg/dL). Immunology tests showed elevated anti-MPO ANCA titers. A renal biopsy showed the presence of pauci-immune crescentic glomerulonephritis, confirming the diagnosis of ANCA-mediated vasculitis. The patient was treated with plasmapheresis and 500 mg of intravenous methylprednisolone for three days, followed by cyclophosphamide and a medium dose of prednisone. Her kidney function improved, and she was then discharged to follow-up with pulmonary clinic for initiation of anti-fibrotic. DISCUSSION: ANCA-associated vasculitis (AAV) is a small-vessel vasculitis that can involve multiple organs. Pulmonary involvement has been reported in 25%–80% of cases. Sometimes, it can be the initial manifestation of the disease. The most common form of pulmonary involvement in AAV is diffuse pulmonary nodules, with or without cavitation and pleural effusions. Occasionally, patients can present with fibrosing-ILD, particularly with anti-MPO. This presentation is more prevalent in males and the elderly. Among AAV patients with ILD, UIP is the most frequent radiographic pattern. Non-specific interstitial pneumonia (NSIP) pattern can also be seen. ILD has been linked to increased mortality in AAV patients, particularly those with a UIP pattern. Treatment of fibrosing-ILD in AAV patients is not well established, with a questionable role for immunosuppression. Anti-fibrotic agents might be helpful in patients with a UIP pattern. CONCLUSIONS: UIP is rarely associated with AAV, and it can be the leading diagnostic manifestation. A careful clinical history and laboratory evaluation should be performed in patients with UIP to identify and treat any underlying systemic disease. UIP is a poor prognostic sign in AAV. Clinical trials are needed to establish the role of anti-fibrotic in treating this condition. Reference #1: Maillet T, Goletto T, Beltramo G, Dupuy H, Jouneau S, Borie R, Crestani B, Cottin V, Blockmans D, Lazaro E, Naccache JM, Pugnet G, Nunes H, de Menthon M, Devilliers H, Bonniaud P, Puéchal X, Mouthon L, Bonnotte B, Guillevin L, Terrier B, Samson M; French Vasculitis Study Group (FVSG). Usual interstitial pneumonia in ANCA-associated vasculitis: A poor prognostic factor. J Autoimmun. 2020 Jan;106:102338. doi: 10.1016/j.jaut.2019.102338. Epub 2019 Sep 27. PMID: 31570253. Reference #2: Mohammad AJ, Mortensen KH, Babar J, Smith R, Jones RB, Nakagomi D, Sivasothy P, Jayne DRW. Pulmonary Involvement in Antineutrophil Cytoplasmic Antibodies (ANCA)-associated Vasculitis: The Influence of ANCA Subtype. J Rheumatol. 2017 Oct;44(10):1458-1467. doi: 10.3899/jrheum.161224. Epub 2017 Aug 1. PMID: 28765242. Reference #3: Zhou P, Ma J, Wang G. Impact of interstitial lung disease on mortality in ANCA-associated vasculitis: A systematic literature review and meta-analysis. Chron Respir Dis. 2021 Jan-Dec;18:1479973121994562. doi: 10.1177/1479973121994562. PMID: 33605150; PMCID: PMC7897823. DISCLOSURES: No relevant relationships by Mais Abdou No relevant relationships by Khaled Alshabani

RETROSPECTIVE STUDY OF PATIENTS WITH MYELODYSPLASTIC NEOPLASM WITH RING SIDEROBLASTS AT UNIVERSITY CENTERS IN NORTHEAST OF BRAZIL

The myelodysplastic neoplasms (MDS) consist of hematopoietic neoplasms originated in the bone marrow and characterized by dysfunctional hematopoiesis, cytopenias, and dysplasia, which is currently diagnosed using clinical, morphological and genetic parameters. A particular subtype of this disease, MDS with ring sideroblasts (MDS-RS), presents with an abnormal accumulation of perinuclear mitochondrial iron in erythroid precursors and a low risk of progression to acute myeloid leukemia. Therefore, a retrospective longitudinal observational study was conducted with 31 patients diagnosed with MDS-RS at two tertiary hospitals in Fortaleza, Ceará. The clinical characteristics and the results of karyotype, as well as the transfusion dependence of patients were evaluated. From these 31 patients, 16 (51.6%) are female and 15 (48.4%) are male. 18 had normal karyotype (58.1%), and 13 had altered karyotype (41,9%). As for cytogenetic abnormalities, it was observed that of these 13 patients, 2 patients had Y nullisomy (15.3%), 2 had chromosome 11 deletion (15.3%), 1 manifested chromosome 20 deletion (7.7%), 2 (15.3%) with chromosome 5 deletion, 1 exhibited chromosome 7 deletion (7.7%), 1 presented trisomy of chromosome 8 (7.7%), and 4 had other alterations (31%). In regard to risk stratification of these 30 patients, 29 had very low or low risk (93.5%) and 2 had intermediate risk (6.5%). Considering transfusion dependence, 11 were dependent (35.5%) and 20 were not (64.5%). From these 11 patients who underwent transfusion 2 (18.1%) had this terapy at diagnosis and 9 (81.9%) after first-line treatment. Low-risk MDS is a heterogeneous group of disorders – clinically, pathologically, and even molecularly. Despite being generally considered a low-risk subtype of MDS, with generally good prognosis, MDS-RS is an entity with diverse clinical presentations, characterized by transfusion dependence and a range of cytogenetic alterations as demonstrated in this study. High risk of developing transfusion dependence is frequently observed and refractoriness to erythropoietin is now considered formal indication to the new approved TGF-β inhibitor, luspatercept. Therefore, it is necessary to accurately evaluate patients, including iron staining in diagnosis workup, and to perform risk stratification before decision making. In conclusion, it can be stated that clinical and correct laboratory evaluation of individuals with MDS-RS is essential to ensure a better understanding of the patient's condition and to identify important prediction factor of response to therapy.