Clinical Laboratory Tests Research Articles

Preliminary Exploration of Al18F-NOTA-FAPI-04 PET/CT in the Management of Ankylosing Spondylitis: A Prospective Clinical Study

Background Ankylosing spondylitis (AS) is characterized by inflammation and osteoblastic changes in the sacroiliac joint. As a potential imaging method for the early assessment of AS, positron emission tomography (PET) can quantify systemic disease activity, which is conducive to monitoring the progression of disease activity and assisting in evaluating the efficacy of the treatment. Objective The study was to evaluate the diagnostic value of aluminium-[18F]fuoride(Al18F)-labelled fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in AS and to investigate its ability to assess disease activity during the development of AS. Material and Methods Twenty AS participants who met the Assessment of SpondyloArthritis international Society criteria and were in an active disease stage were included in this study from May 2022 to April 2023. Sixteen healthy controls were also inrolled. All participants underwent Al18F-NOTA-FAPI-04 PET/CT imaging after collecting clinical assessment and laboratory results. The correlation between positive joint count (PJC) and systemic joint standard uptake value ratio (SUVR, the mean SUVmax of the 5 highest joints/SUVmax of the uninvolved sacrum) on PET and clinical disease activity assessment and various laboratory tests were analyzed. Results A total of 2820 joints were observed in 20 participants (median age 34.5,[21-61]range, 15 men), with a PJC of 1300 (46.7%), and 39 positive uptakes were found in 40 sacroiliac joints (97.5%). PET/CT images revealed FAPI-04 uptake in both sacroiliac joints in 2 participants without radiographic sacroiliitis in the early stages of AS and varying degrees of uptake in the sacroiliac joints and spinal joints in the remaining participants. PJC and SUVR were positively correlated with most clinical assessments and laboratory findings ( P < .05), and SUVR of the sacroiliac joint was positively correlated with C-reactive protein (CRP) (mg/L; r = 0.498, P = .026). Conclusion Al18F-NOTA-FAPI-04 PET/CT was highly sensitive to systemic arthritic changes in AS participants and correlated with clinical disease activity and laboratory tests.

Smartwatch-based algorithm for early detection of pulmonary infection: Validation and performance evaluation.

The proliferation of smart devices provides the possibility of early detection of the signs of pulmonary infections (PI). This study validates a smartwatch-based algorithm to monitor the risk of PI in adults. An algorithm that runs on smartwatches was developed and tested in 87 patients with PI and 408 healthy subjects. The algorithm examines heart rate variability, respiratory rate, oxygen saturation, body temperature, and cough sound. It was embedded into the Respiratory Health Study app for a smartwatch to detect the risk of PI and was further validated in the hospital. Doctors diagnosed PI using a clinical evaluation, lab tests, and imaging examination, the gold standard for diagnosis. The accuracy, sensitivity, and specificity of the algorithm predicting PI were evaluated. In all, 80 patients with PI and 85 healthy volunteers were recruited to validate the accuracy of the algorithm. The area under the curve of the algorithm for predicting PI was 0.86 (95% confidence interval: 0.82-0.91) (P < 0.001). Compared to the gold standard, the overall accuracy of the algorithm was 85.9%, the sensitivity was 81.4%, and the specificity was 90.4%. The algorithm for heart rate, respiratory rate, oxygen saturation, and body temperature had an accuracy of 68.2%, and the accuracy of the algorithm including cough sound was 82.6%. Our wearable system facilitated the detection of risk of PI. Multi-source features were useful for enhancing the performance of the lung infection screening algorithm. Chinese Clinical Trial Registry of the International Clinical Trials Registry Platform of the World Health Organization ChiCTR2100050843; https://www.chictr.org.cn/showproj.html?proj = 126556.

Clinical Aspects of Somatic Comorbidities in Gas and Electric Welders

Introduction: Health effects of welding fumes in workers are not limited to fibrosis and irritation of the respiratory tract. Inhalation of a complex mixture of particles and gases from the workplace air can cause damage to the central nervous system and higher incidence of nonoccupational diseases attributed to toxic, allergic, and carcinogenic effects of this risk factor. Objective: To study characteristics of somatic comorbidities in welders with occupational diseases of the respiratory system. Materials and methods: The study involved 140 male patients aged 48 to 60 years suffering from occupational respiratory diseases. The main (first) group included gas and electric welders while the reference group consisted of miners and millers with silica-related lung diseases. The mean occupational exposure to industrial aerosols in the groups was 22.8 ± 6.7 and 22.3 ± 6.9 years, respectively. We conducted a questionnaire-based survey and clinical laboratory testing of the workers. The intergroup differences were considered statistically significant at p &lt; 0.05. Results: We established that lesions of the mucous membrane of the esophagus, stomach and duodenum were the most prevalent comorbidities in the electric welders (72.7 %), followed by dyslipidemia (47.3 %), stage I hypertension (36.4 %), liver diseases (31.8 %), kidney damage (31.1 %), stage II and III hypertension (27.8 %). Coronary heart disease and diabetes mellitus were much less frequent and observed in only 4.5 % of the welders. Mucosal lesion of the upper gastrointestinal tract and liver diseases were more prevalent in the welders compared to the reference group. Study limitations: Statistical analysis was carried out using a nonparametric test to compare two independent samples. Conclusions: Exposure to welding fumes inducing occupational respiratory diseases increases the frequency of a combination of such nonoccupational diseases as lesions of the mucous membrane of the upper gastrointestinal tract and liver damage.

Exploration of pharmacokinetic differences between East Asians and Caucasians: insights from pharmacokinetic studies in healthy subjects.

Interethnic differences in the pharmacokinetics of drugs result from a complex interplay of environmental, genetic, and demographic factors. Identifying ethnic differences in pharmacokinetics is challenging due to the multifaceted contributions of the underlying factors. To address these challenges, this paper reviews 9 pharmacokinetic studies meeting the following criteria: (A) Conducted at Seoul National University Hospital from 2013 to 2022 as a single-center study. (B) Pharmacokinetic studies involving both East Asians (Korean, Japanese, or Chinese) and Caucasians. (C) Study drugs were administered orally. (D) Raw data was provided for reanalysis. This retrospective analysis aimed to investigate the existence of ethnic differences in drug exposure and understand the possible factors contributing to these variabilities. Pharmacokinetic, demographic, and clinical laboratory test data were analyzed to assess potential pharmacokinetic differences between East Asians and Caucasians. This assessment involved calculating the geometric mean ratio of dose-normalized area under the time-concentration curve (AUC) and dose- and weight-normalized AUC, along with their 90% confidence intervals. Additionally, pharmacological information, including metabolic pathways, was gathered from the investigational brochure or the respective country's drug label. Among 9 studies, 4 studies demonstrated approximately 1.3 to 1.8 times higher drug exposure in East Asians compared to Caucasians. These drugs were primarily eliminated through hepatic metabolism, with less than 5% excreted unchanged in the urine. Two drugs were metabolized by hepatic cytochrome P450 3A4, one by glutathione S-transferase, and specific metabolic pathways for another drug were not identified. Further research is needed to assess the causes of ethnic variability in these drugs.

A study on the diagnostic and predictive value of neutrophil-to-lymphocyte ratio for early perforation in acute appendicitis

Objective To investigate the predictive value of neutrophil-to-lymphocyte ratio (NLR) for early perforation of the appendix in patients with acute appendicitis (AA). Methods Two hundred and 80eighty patients with the first episode of AA within 48 hours and not yet treated with antibiotics were included in this study retrospectively; divided into two groups by the presence or absence of perforation. The clinical data, traditional inflammatory indexes, and NLR were compared between the two groups. The predictive value of inflammatory indexes on the early appendiceal perforation was explored. Results Patients in the perforated group were older, with higher blood WBC, NEU% and NLR, lower LYM% and PLT, higher serum CRP and PCT, and longer hospitalization time. Multivariate regression analysis revealed that high WBC, NEU%, NLR, CRP, PCT, and low LYM% were independent risk factors for early appendiceal perforation. The ROC curves revealed that the predictive value of WBC, CRP, and PCT for early appendiceal perforation was low. NLR, LYM%, and NEU% had a higher predictive value, with AUC values of 0.947, 0.928, and 0.920, respectively. NLR had the highest predictive value. The diagnostic Cut-off value of NLR is 10.83 with a sensitivity of 0.963, and a specificity of 0.850. Conclusion NLR can be used as an effective and sensitive predictive maker of early appendiceal perforation in AA patients. It is easy to generate from existing routine clinical laboratory testing for AA and can be included in complete blood count (CBC) as a routine or add-on value.

Predicting early gastric cancer risk using machine learning: A population-based retrospective study.

Early detection and treatment are crucial for reducing gastrointestinal tumour-related mortality. The diagnostic efficiency of the most commonly used diagnostic markers for gastric cancer (GC) is not very high. A single laboratory test cannot meet the requirements of early screening, and machine learning methods are needed to aid the early diagnosis of GC by combining multiple indicators. Based on the XGBoost algorithm, a new model was developed to distinguish between GC and precancerous lesions in newly admitted patients between 2018 and 2023 using multiple laboratory tests. We evaluated the ability of the prediction score derived from this model to predict early GC. In addition, we investigated the efficacy of the model in correctly screening for GC given negative protein tumour marker results. The XHGC20 model constructed using the XGBoost algorithm could distinguish GC from precancerous disease well (area under the receiver operating characteristic curve [AUC] = 0.901), with a sensitivity, specificity and cut-off value of 0.830, 0.806 and 0.265, respectively. The prediction score was very effective in the diagnosis of early GC. When the cut-off value was 0.27, and the AUC was 0.888, the sensitivity and specificity were 0.797 and 0.807, respectively. The model was also effective at evaluating GC given negative conventional markers (AUC = 0.970), with the sensitivity and specificity of 0.941 and 0.906, respectively, which helped to reduce the rate of missed diagnoses. The XHGC20 model established by the XGBoost algorithm integrates information from 20 clinical laboratory tests and can aid in the early screening of GC, providing a useful new method for auxiliary laboratory diagnosis.

TORCH serological marker on cholestasis with the occurrence of biliary atresia and its clinical manifestations

Background and objectives. Biliary atresia occurs due to multifactorial etiology, and it was recently suggested that perinatal infection with TORCH, especially Cytomegalovirus (CMV), triggers inflammation of the bile ducts. This study aims to evaluate the TORCH infection on cholestasis with the occurrence of biliary atresia and its clinical manifestations. Materials and methods. A prospective single-center study was performed on 113 cholestatic infants and classified into two groups based on their positivity of immunoglobulin M and G (IgM and IgG). They were tested for CMV, Rubella, and Toxoplasmosis by a Gold Standard Diagnostics ELISA kit in our laboratory. Clinical conditions, laboratory tests (Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and liver histopathology between the two groups were analyzed with p &lt;0.05 was considered significant. Results. Out of 113 infants of cholestasis, 94.7% (n = 107) were CMV IgG-positive, followed by Rubella IgG-positive (47.8%, n=54). Rubella and toxoplasma IgM antibodies were least commonly found in cholestasis (8% and 7.1%, respectively). CMV IgG-positive status was noted to be older at the onset of jaundice. Infants with Rubella IgG-positive had less incidence of extrahepatic cholestasis (37.7% vs 62.3%) and liver fibrosis (39% vs 61%) (p&lt;0.05). There was no difference in sex, birth weight, gestational age, AST, ALT, GGT, coagulation hemostasis, and abdominal USG abnormality based on torch serological markers (p&gt;0.05). Conclusion: CMV infection mostly occurs in infants with cholestasis, followed by rubella infection. TORCH infection screening may be necessary in all infants with cholestasis.

Covid-19: Course and prognosis in patients with severe clinical form

Our aim is to identify factors of unfavorable prognostic significance in hospitalized patients with severe COVID-19, an analysis of clinical and demographic characteristics and routine laboratory tests was performed. For the following period: March - July 2023, 25 patients with severe COVID-19 needing intensive care and treatment were hospitalized in Military Medical Academy Sofia (Bulgaria). The diagnosis has been confirmed by RT-PCR analysis for SARS-CoV-2 detection. According to the prognosis, the target group of patients were divided into two groups - discharger and deceased. The average age of the analyzed cohort was 77.6 years. The most commonly reported clinical symptoms include fever, cough, shortness of breath, and neurological symptoms. We found that all patients with severe COVID-19 were comorbid and elderly. The average hospital stay in intensive care is 11.9 days. Nearly half of the cases had fatal outcome (12/25). Among the factors associated with the clinical severity of COVID-19 and mortality are advanced age, presence of chronic concomitant diseases, development of pneumonia and/or neurological complications, as well as deviations in some laboratory parameters.

Hipoparatiroid: Deteksi Awal dan Cara Penegakan Diagnosis

Hypoparathyroidism is an endocrine disorder characterized by low or even absent production of parathyroid hormone (PTH). The most common cause of hypoparathyroidism is injury to the parathyroid gland or accidental removal during thyroid surgery. The diagnosis of hypoparathyroidism is made by assessing clinical symptoms, physical examination and laboratory tests. The author wants to know more about how to detect early and diagnose hypoparathyroidism. Hypoparathyroidism is an endocrine disorder characterized by low or absent production of parathyroid hormone (PTH). The most common cause of hypoparathyroidism is injury to the parathyroid glands or unintentional removal during thyroid surgery. The diagnosis of hypoparathyroidism is established through the assessment of clinical symptoms, physical examination, and laboratory tests. The author aims to explore further the early detection and diagnostic approaches for hypoparathyroidism.

A hybrid feature selection approach for urinary tract infection detection and prediction in IoT-Fog environment

Urinary Tract Infections (UTIs) are a prevalent health concern experienced by millions of individuals worldwide and have a significant impact on overall well-being. The clinical presentation of UTIs varies depending on their location and severity. Common symptoms include discomfort during urination, increased frequency, a compelling urge to urinate, discomfort in the lower abdomen, and the presence of blood in the urine (hematuria). Severe cases may be accompanied by fever, pain in the flank region, and other systemic symptoms, indicative of an upper UTI. Precise diagnosis of UTIs is achieved through clinical evaluation and laboratory tests. The primary aim of this research is to utilize appropriate Machine Learning (ML)-based algorithms to predict Urinary Tract Infections (UTIs). The ultimate goal is to develop a predictive model that can be effectively implemented in a smart toilet system. By achieving this objective, this research seeks to provide an innovative and pragmatic solution for UTI prediction, harnessing the potential of ML algorithms in IoT-Fog settings to enhance healthcare and promote public health. This paper introduces a hybrid approach that combines feature selection methods and employs the Guided Regularized Random Forest (GRRF) classification algorithm to aid in the diagnosis of UTIs. A UTI dataset was created using data from routine examinations and definitive diagnostic outcomes for UTI patients. Dimensionality reduction was carried out using Principal Component Analysis (PCA), while feature selection was performed using K-best and Lasso CV techniques. Through the proposed strategy, this study achieved a remarkable accuracy rate of 98.8% and a precision rate of 98.90% in UTI identification. Future UTI prevention and treatment plans must be optimized via further research and ongoing efforts to overcome antibiotic resistance.

Safety, Tolerability, Pharmacokinetics, and Immunogenicity of the Anti-IFNAR1 Monoclonal Antibody QX006N: A First-in-Human Single Ascending Dose Study in Healthy Chinese Volunteers.

QX006N is a novel, humanized, IgG4κ monoclonal antibody targeting IFNAR1, developed for the treatment of systemic lupus erythematosus. This study aims to investigate the pharmacokinetics, safety, tolerability, and immunogenicity of QX006N when administered intravenously to healthy Chinese individuals. A double-blind, randomized, placebo-controlled, single-ascending-dose, phase I clinical trial was conducted comprising five cohorts (n = 10 per cohort, except n = 5 for the first cohort). Subjects in each cohort were randomly assigned in a 4:1 ratio to receive a single intravenous infusion of QX006N (0.3 mg/kg, 1.0 mg/kg, 3.0 mg/kg, 6.0 mg/kg, or 10.0 mg/kg) or placebo for 30 minutes. Tolerability assessments included adverse events, vital signs, 12-lead electrocardiogram, physical examination, and clinical laboratory tests. The serum concentration of QX006N was measured using the enzyme-linked immunosorbent assay method, and the anti-drug antibodies were detected using the electrochemiluminescence assay method. QX006N demonstrated a favorable safety and tolerability profile throughout the study. All treatment-emergent adverse events were of Grade 1-2 (CTCAE Version 5.0), and no serious adverse events, deaths, or drug discontinuations because of treatment-emergent adverse events were observed. All drug-related treatment-emergent adverse events showed no clear dose-related trends. Following an intravenous infusion of QX006N at doses that ranged from 0.3 mg/kg to 10 mg/kg, the half-life increased from 24.7 to 208 hours in a dose-dependent manner, while clearance decreased from 0.0828 to 0.0065 L/h. The maximum concentration exhibited nearly dose-proportional increases, and the area under the curve displayed a more than dose-proportional increment with non-linear pharmacokinetic characteristics. The incidence of anti-drug antibodies was observed to increase over time for doses that ranged from 1.0 mg/kg to 10.0 mg/kg of QX006N, reaching its peak at day 57 (range 62.50-87.50%). Conversely, the incidence of anti-drug antibodies in the QX006N 0.3-mg/kg and placebo cohorts remained low. QX006N demonstrated acceptable safety, tolerability, and pharmacokinetic characteristics in healthy subjects when administered as a single intravenous infusion at doses that ranged from 0.3 mg/kg to 10.0 mg/kg. Based on the pharmacokinetic and safety outcomes, a recommended effective dose of 300 mg is proposed for future phase Ib studies. This study has been registered at http://www.chinadrugtrials.org.cn/ under identifier CTR20212834.

Healthcare Risk Management and Countermeasures of Clinical Medical Laboratory Testing

Clinical laboratory test-data report is not only an important basis for clinical diagnosis and treatment, but also an important medical evidence. However, at present, in clinical practice, there is a general situation that the medical test-data report have no pay necessary attention in medicine evidence. As a result, in cases of medical malpractise disputes, the medical test-data report often becomes the evidence of litigation against the hospital. This study aims to analyze the healthcare risks in clinical medical laboratory testing and propose effective risk management strategies. The article first identifies key risk points in clinical medical laboratory testing, including risks before, during, and after testing, as well as other related risks. It then discusses existing issues in healthcare risk management, such as non-standardized testing processes, inadequate risk warning mechanisms, and insufficient credibility of test results. Based on these analyses, the article puts forward targeted management strategies, including standardizing testing processes, improving warning mechanisms, and enhancing the credibility of test results. The purpose of this study is to enhance the safety and accuracy of clinical medical laboratory testing, reduce healthcare risks, and ensure patient safety.

Foodborne Diseases: A Study before and during the COVID-19 Pandemic in Brazil.

Foodborne Diseases (FBDs) are a worldwide problem and occur after contaminated food has been ingested, signaling a lack of food quality. Even though the SARS-CoV-2 virus is not transmitted through food, the COVID-19 pandemic has caused several challenges worldwide that have had direct implications on food production and handling, stimulating and reinforcing the adoption of good manufacturing and food handling practices. The aim of this study was to analyze data on notifications of FBD in Brazil in the years before (2018 and 2019) and during (2020 and 2021) the COVID-19 pandemic. Secondary data from the National System of Notifiable Diseases was analyzed, evaluating: overall incidence rate, lethality and mortality, contamination sites, and criteria for confirming the etiological agent. There were 2206 records of FBDs, and the mortality rate was 0.5% in both periods. The incidence rate before the pandemic was 6.48 and during the pandemic was 3.92, while the mortality coefficient was 0.033 before and 0.019 during the pandemic, both per 100,000 inhabitants. There was no significant difference in the number of FBD notifications in the evaluated periods. There was a migration of the location of FBD, with a significant increase in FBD notifications in hospitals and health units and a reduction in notifications from social events. There was a significant increase in the type of criteria used to confirm outbreaks, with an increase in clinical laboratory tests and clinical reports for bromatology. The increase in notifications in hospitals and health units demonstrates the necessity of improving food safety knowledge and the attitudes and practices of food handlers and healthcare professionals.

Clinical analysis of 86 cases of acute fatty liver of pregnancy

Objective: To investigate the clinical characteristics and maternal and fetal prognosis of pregnant women with acute fatty liver of pregnancy (AFLP). Methods: The clinical data of 86 AFLP pregnant women admitted to the Third Affiliated Hospital of Guangzhou Medical University from September 2017 to August 2022 were collected, and their general data, clinical characteristics, laboratory tests and maternal and fetal outcomes were retrospectively analyzed. Results: (1) General information: the age of the 86 pregnant women with AFLP was (30.8±5.4) years, and the body mass index was (21.0±2.5) kg/m2. There were 50 primiparas (58.1%, 50/86) and 36 multiparas (41.9%, 36/86). There were 64 singleton pregnancies (74.4%, 64/86) and 22 twin pregnancies (25.6%, 22/86). (2) Clinical characteristics: the main complaints of AFLP pregnant women were gastrointestinal symptoms, including epigastric pain (68.6%, 59/86), nausea (47.7%, 41/86), anorexia (46.5%, 40/86), vomiting (39.5%, 34/86). The main non-gastrointestinal symptoms were jaundice of skin and/or scleral (54.7%, 47/86), edema (38.4%, 33/86), fatigue (19.8%, 17/86), bleeding tendency (16.3%, 14/86), polydipsia or polyuria (14.0%, 12/86), skin itching (8.1%, 7/86), and 17.4% (15/86) AFLP pregnant women had no obvious symptoms. (3) Laboratory tests: the incidence of liver and kidney dysfunction and abnormal coagulation function in AFLP pregnant women was high, and the levels of blood ammonia, lactate dehydrogenase and lactic acid were increased, and the levels of hemoglobin, platelet and albumin decreased. However, only 24 cases (27.9%, 24/86) of AFLP pregnant women showed fatty liver by imageology examination. (4) Pregnancy outcomes: ① AFLP pregnant women had a high incidence of pregnancy complications, mainly including renal insufficiency (95.3%, 82/86), preterm birth (46.5%, 40/86), hypertensive disorders in pregnancy (30.2%, 26/86), gestational diabetes mellitus (36.0%, 31/86), fetal distress (24.4%, 21/86), pulmonary infection (23.3%, 20/86), disseminated intravascular coagulation (16.3%, 14/86), multiple organ dysfunction syndrome (16.3%, 14/86), hepatic encephalopathy (9.3%, 8/86), and intrauterine fetal death (2.3%, 2/86). ② Treatment and outcome of AFLP pregnant women: the intensive care unit transfer rate of AFLP pregnant women was 66.3% (57/86). 82 cases were improved and discharged after treatment, 2 cases were transferred to other hospitals for follow-up treatment, and 2 cases (2.3%, 2/86) died. ③ Neonatal outcomes: except for 2 cases of intrauterine death, a total of 106 neonates were delivered, including 39 cases (36.8%, 39/106) of neonatal asphyxia, 63 cases (59.4%, 63/106) of neonatal intensive care unit admission, and 3 cases (2.8%, 3/106) of neonatal death. Conclusions: AFLP is a severe obstetric complication, which is harmful to mother and fetus. In the process of clinical diagnosis and treatment, attention should be paid to the clinical manifestations and laboratory tests of pregnant women, early diagnosis and active treatment, so as to improve maternal and fetal outcomes.

Compassionate Use Narsoplimab for Severe Refractory Transplantation-Associated Thrombotic Microangiopathy in Children

Transplant-associated thrombotic microangiopathy (TA-TMA) is a common and potentially severe complication of hematopoietic cell transplantation. TA-TMA-directed therapy with eculizumab, a complement C5 inhibitor, has resulted in a survival benefit in some studies. However, children with TA-TMA refractory to C5 inhibition with eculizumab (rTA-TMA) have mortality rates exceeding 80%, and there are no other known therapies. Narsoplimab, an inhibitor of the MASP-2 effector enzyme of the lectin pathway, has been studied in adults with TA-TMA as first-line therapy with a response rate of 61%. Although there are limited data on narsoplimab use as a second-line agent in children, we hypothesized, that complement pathways proximal to C5 are activated in rTA-TMA, and that narsoplimab may ameliorate rTA-TMA in children. In this single-center study, children were enrolled on single-patient, Institutional Review Board-approved compassionate use protocols for narsoplimab treatment. Clinical complement lab tests were obtained at the discretion of the treating physician, although all patients were also offered participation in a companion biomarker study. Research blood samples were obtained at the time of TA-TMA diagnosis, prior to eculizumab treatment, at the time of refractory TA-TMA diagnosis prior to the first narsoplimab dose, and 2 weeks after the first narsoplimab dose. Single ELISA kits were used to measure markers of complement activation according to the manufacture's instructions. Five children with rTA-TMA received narsoplimab; 3 were in multiorgan failure and 2 had worsening multiorgan dysfunction at the time of treatment. Additional comorbidities at the time of treatment included sinusoidal obstructive syndrome (SOS; n = 3), viral infection (n = 3), and steroid-refractory stage 4 lower gut grade IV acute graft-versus-host disease (aGVHD, n = 3). Two infants with concurrent SOS and no aGVHD had resolution of organ dysfunction; 1 also developed transfusion-independence (complete response), and the other's hematologic response was not assessable in the setting of leukemia and chemotherapy (partial response). One additional patient achieved transfusion independence but had no improvement in organ manifestations (partial response), and 2 patients treated late in the course of disease had no response. Narsoplimab was well tolerated without any attributed adverse effects. Three patients consented to provide additional research blood samples. One patient with resolution of organ failure demonstrated evidence of proximal pathway activation prior to narsoplimab treatment with subsequent declines in Ba, Bb, C3a, and C5a and increases in C3 in both clinical and research lab tests. Otherwise, there was no clear pattern of other complement markers, including MASP-2 levels, after therapy. In this cohort of ill children with rTA-TMA and multiple comorbidities, 3 patients benefited from narsoplimab. Notably, the 2 patients with resolution of organ involvement did not have steroid-refractory aGVHD, which is thought to be a critical driver of TA-TMA. Additional studies are needed to determine which patients are most likely to benefit from narsoplimab and which markers may be most helpful for monitoring lectin pathway activation and inhibition.

SEX DIFFERENCES IN THE LINK BETWEEN DNA METHYLATION–BASED BIOLOGICAL AGING AND HEALTH IN OLDER INDIVIDUALS

Abstract It is well-established that women live longer than men, however, sex differences in biological aging have not been consistently reported, and may differ depending on the measure used. This study aimed to determine the correlation between DNA methylation (DNAm) age acceleration (AA) measures, with system-wide frailty-index (FI) aging and brain-predicted age difference (brain-PAD), in an initially healthy population of men and women aged ≥70 years. We additionally explored the extent to which these AA measures were associated with clinical measures, and chronic conditions, separately in men and women. DNAm age (Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE) were estimated in blood from 560 Australians (women, 50.7%) enrolled in the ASPREE study. FI was a deficit accumulation of 67 items including cognition and morbidities. Brain age was estimated from T1-weighted MRI. Clinical measurements, laboratory tests, and self-reports were used to identify chronic illnesses. FI had the strongest correlation with GrimAA and DunedinPACE (range r: 0.20 to 0.24 in both sexes) but was not associated with HorvathAA. Brain-PAD was not correlated with any biological aging measure. Correlations between AA and clinical measures were more commonly found in women than men and were the strongest for DunedinPACE and clinical measures including grip strength, gait speed, and self-rated health (r: -0.23 to 0.24). AA measures, especially GrimAA and DunedinPACE, were significantly associated with hypertension, diabetes, chronic kidney disease in men, and obesity and depression in women. Our findings highlight the importance of considering sex differences when investigating the link between biological age and clinical measures.

Diagnosis and Treatment of a Case of Maxillary Cleft in a Cat Associated with Pulmonary Emphysema

Maxillary cleft in cats often occurs due to high-altitude falls, resulting in trauma and pulmonary emphysema. Clinically, it is characterized by oral and nasal bleeding and is classified into congenital and acquired types, with its etiology being related to husbandry practices. This paper presents a case of maxillary cleft in a cat associated with pulmonary emphysema. After initial symptom observation and inquiry, a definitive diagnosis was made through clinical examination, laboratory tests, and X-ray imaging. Treatment involving medication and surgery was administered, followed by an evaluation of its effectiveness. Given the limited literature on this condition and its increasing incidence, this case contributes to the guidance of diagnosis and treatment for cats with maxillary cleft associated with pneumothorax.

Metanalysis of the Diagnostic Performance of Western Blot for the Early Diagnosis of Congenital Toxoplasmosis

BACKGROUND: Congenital toxoplasmosis is an infection caused by the Toxoplasma gondii a protozoa obligate intracellular parasite that appears after a mother´s primary infection occurs during pregnancy. The congenital infection can cause severe symptoms such as: hydrocephalus, intracranial calcifications, seizures, hepatosplenomegaly, and chorioretinitis, leading to irreversible neurological and ocular lesions. Its early diagnosis is critical to obtain good outcomes after treatment where the western blot is considered as the gold standard. Western blot discriminate antibodies for specific proteins of the microorganism enabling differentiation between antibodies transmitted by mother from those elaborated by the newborn (compared immunological profiles) and can be obtained commercially or be elaborated by the clinical laboratory test (“house made”). However, there is not metanalysis about the diagnostic properties of the test that can support evidence-based recommendations for its use. METHODS: The research terms used were: “congenital toxoplasmosis” and “western blot”. Databases for bibliographic searches were PubMed and Scopus, without restriction of date or language. Selection criteria were studies of evaluation of the diagnostic performance of western blot assay that included newborn with a definitive diagnosis of congenital infection by Toxoplasma according to the European network case definition (IgG anti-Toxoplasma persistent at 10 months of age) and controls that were defined by IgG antibodies that disappears in the serum of children in absence of treatment before six months of age. Screening and literature selection was done by the four researchers and disagreement were settled by reaching a consensus by discussion with mentor to avoid the erroneous exclusion of eligible articles. The PRISMA statement (http://www.prisma-statement.org/) was followed for quality assessment of the manuscript. The data were organized in an evidence table matrix, and sensitivity, specificity, and diagnostic odds ratio (DOR) index were calculated. RESULTS: Of 44 articles related to the search terms were found in literature databases, 10 fulfill criteria to be included in the metanalysis. The sensitivity obtained was 93.8 (95 CI: 79.2-98.4) and the specificity of 96.6% (95 CI: 89.8-98.9). However, heterogeneity was observed between the studies. Causes for heterogeneity were the different methods to elaborate the western blot assay. Commercial methods showed better performance that homemade methods. The results suggest that better accuracy can be obtained by using standardized commercial test. CONCLUSION: In conclusion, the meta-analysis supports the use of the Western Blot test as an effective method for the diagnosis of congenital toxoplasmosis in terms of sensitivity and specificity. However, further research is needed to establish more accuracy regarding sensitivity and specificity in the diagnosis in different settings by using well standardized assays.

Use of Methotrexate for More Than 4 Years Is Not Associated with Liver Fibrosis in Rheumatoid Arthritis Patients

Background. Methotrexate is an anchor drug in the management of rheumatoid arthritis (RA). However, the association between methotrexate and development of liver fibrosis remains a subject of controversy. Non-invasive methods to assess liver fibrosis, such as the FIB-4 score, have been developed. RA patients on methotrexate therapy should be monitored for any signs of liver fibrosis. This study aims to investigate the correlation between methotrexate cumulative dose and the FIB-4 score in rheumatoid arthritis patients who received methotrexate therapy to assess the hepatotoxic effects of methotrexate.&#x0D; Methods. This cross-sectional study involved rheumatoid arthritis patients who received methotrexate therapy at Dr. Hasan Sadikin General Hospital Bandung from September 2022 to November 2022. Clinical data, laboratory tests (including platelet values and liver function test), and cumulative methotrexate doses were extracted from medical records. Data were analyzed using the Spearman correlation test.&#x0D; Results. This study involved 100 subjects aged between 22-82 years, comprising 93% women and 7% men. The median FIB-4 score was 0.73 (0.24-6.80), while the median methotrexate cumulative dose was 2477.5 mg, with a range of 1005-10400 mg. The results showed that correlation coefficient between the FIB-4 score and methotrexate cumulative dose in rheumatoid arthritis patients was -0.089 (p=0.378).&#x0D; Conclusion. There is no significant correlation between FIB-4 score and cumulative dose of methotrexate in rheumatoid arthritis patients. The use of methotrexate in RA patients over 4 years is relatively safe as it does not increase the risk of liver fibrosis.

CLINICAL AND TYPICAL IMAGING CHARACTERISTICS OF CRYPTOCOCCAL MENINGITIS IN HIV INFECTED PATIENT: A CASE REPORT

Although Cryptococcal infection is worldwide distribution, it is more seen in the immunocompromised patients. Cryptococcus neoformans is the most common central neurvous system fungal pathogen in HIV infected patients. Besides clinical features and laboratory tests, imaging findings play an important role in the evaluation of cryptococcal infection. In this paper we present an immunocompromised HIV infected case of C. neoformans meningitis with clinical features and imaging characteristics by MR image.