Laboratory Criteria Research Articles

Review of Diagnostic Challenges and Literature Data in Paraneoplastic Limbic Encephalitis: A Case Presentation

Abstract Paraneoplastic limbic encephalitis is a rare condition reported in practice. It is most commonly associated with small cell lung cancer (SCLC). This case report is offered to aid physicians in making informed decisions about timing and type of treatment and is evident, that quick diagnosis is critical for both, neurologists and oncologists. The presentation reviews the case of a female patient diagnosed with limbic encephalitis. Further research is needed to establish clinical, laboratory and instrumental criteria that may be related to outcomes. The purpose of this paper is to present the potential repercussions of a delayed diagnosis and highlight the beneficial results of specific investigations and symptomatic therapy. Comprehensive familiarity with clinical presentations and the limitations of current diagnostic procedures is imperative for neurologists. Equally essential is this understanding for radiologists, serving as the basis for accurate diagnostic analyses derived from imaging findings. The intricate nature of neurological disorders sometimes necessitates the cooperation of neurologists, radiologists, and, in this particular instance, oncologists, in order to achieve precise diagnosis and develop successful treatment approaches.

The Liver Cirrhosis Network Cohort Study: Cirrhosis Definition, Study Population, and Endpoints.

One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis. The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee. The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient-reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding because of portal gastropathy, and hepatocellular carcinoma were also codified. The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multicenter cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion. NCT05740358.

Real-World Evidence for Utility of Serum sFlt-1/PlGF Test for Routine Clinical Evaluation of Hospitalized Women with Hypertensive Disorders of Pregnancy

An imbalance of the anti-angiogenic factor, soluble fms-like tyrosine kinase-1 (sFlt-1), and pro-angiogenic factor, placental growth factor (PlGF) in the circulation is a reliable predictor for development of preeclampsia with severe features and related adverse outcomes. In 2023, the United States (US) Food and Drug Administration approved a serum sFlt-1/PlGF test at a cut-off of 40 to aid in the risk assessment of women hospitalized for hypertensive disorders of pregnancy (HDP) for the progression to preeclampsia with severe features between 23 and 35 weeks. The purpose of this study was to generate real-world evidence for clinical utility for serum sFlt-1/PlGF test when made available to clinicians in a timely fashion as an aid in risk stratification of development of preeclampsia with severe features within two weeks of testing among hospitalized patients with HDP. Hospitalized patients with HDP between 23 weeks to 34 weeks and 6 days of gestation were prospectively studied from June 2023 to Jan 2024 following implementation of serum sFlt-1/PlGF testing into routine clinical practice. Serum samples were obtained from patients via venipuncture and analyzed on an automated immunoassay platform (PlGF and sFlt-1 assays; Thermo Fisher Scientific). Before implementation, physicians were educated on appropriate use and management guidelines based on biomarkers but made pragmatic management decisions independently. Results of sFlt-1/PlGF tests were available to clinicians within 24 hours of venipuncture. The association between sFlt-1/PlGF ≥ 40 and progression to preeclampsia with severe features and adverse maternal/perinatal outcomes were assessed. Of the 65 patient encounters, 36 had a sFlt-1/PlGF < 40 (55.4%). The rate of delivery for indications related to HDP within two weeks was significantly lower among encounters with a low ratio versus high ratio (2/36 [5.6%] vs 21/29 [72.4%]) even after controlling for relevant confounders (adjusted HR 7.52, 95% CI: 3.05, 18.54; p < 0.001). A diagnosis of preeclampsia with severe features within two weeks of testing was also less likely among the encounters with sFlt-1/PlGF ratio < 40 when compared to sFlt-1/PlGF ratio ≥ 40 (2/36 [5.6%] versus 23/29 [79.3%], p<0.001; PPV 79% [95% CI: 0.65, 0.94] and NPV 0.94 [95% CI: 0.87, 1.00]). The positive and negative likelihood ratios for the development of preeclampsia with severe features within two weeks of testing were 6.13 and 0.09 respectively. Encounters with an sFlt-1/PlGF ratio <40 were less likely to experience a maternal or fetal adverse event as compared to encounters with sFlt-1/PlGF ratio ≥40 (3/36 [8.3%] vs 10/29 [34.5%], p=0.01). Among 36 encounters involving low sFlt-1/PlGF values, 22 had had equivocal clinical or laboratory criteria resembling preeclampsia at presentation but were expectantly managed based on biomarkers and none developed preeclampsia with severe features or adverse outcomes at two weeks. The median latency defined as days between biomarker measurement and delivery in patients with low biomarker ratio was 33 (IQR 23, 47) versus 7 (IQR 4, 14) days among patients with a high ratio (p<0.001). Corticosteroid use within two weeks was also significantly reduced in the low biomarker group when compared to high biomarker group (8/35 [22.9%] vs 24/29 [82.8%], p<0.001). In this study, incorporation of sFlt-1/PlGF ratio into clinical practice serves as a dependable supplement in assessing risk for progression to preeclampsia with severe features and adverse outcomes in patients with HDP in the US. Among patients with a low ratio, pregnancy may be prolonged which resulted in better neonatal outcomes without harm to the mother.

Antiphospholipid antibodies in patients with antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by recurrent pregnancy morbidity or thrombosis in combination with the persistent presence of antiphospholipid antibodies (aPLs) in plasma/serum. Antiphospholipid antibodies are a heterogeneous, overlapping group of autoantibodies, of which anti-β2-glycoprotein I (aβ2GPI), anticardiolipin (aCL) antibodies and antibodies that prolong plasma clotting time in tests in vitro known as lupus anticoagulant (LAC) are included in the laboratory criteria for the diagnosis of APS. The presence of LAC antibodies in plasma is indirectly determined by measuring the length of coagulation in two tests - activated partial thromboplastin time (aPTT) and diluted Russell's viper venom time (dRVVT). The concentration of aβ2GPI and aCL (immunglobulin G (IgG) and immunoglobulin M (IgM) isotypes) in serum is directly determined by solid-phase immunoassays, either by enzyme-linked immunosorbent assay (ELISA), fluoroimmunoassay (FIA), immunochemiluminescence (CLIA) or multiplex flow immunoassay (MFIA). For patient safety, it is extremely important to control all three phases of laboratory testing, i.e. preanalytical, analytical and postanalytical phase. Specialists in laboratory medicine must be aware of interferences in all three phases of laboratory testing, in order to minimize these interferences. The aim of this review was to show the current pathophysiological aspects of APS, the importance of determining aPLs-a in plasma/serum, with an emphasis on possible interferences that should be taken into account when interpreting laboratory findings.

Animal Experiments and Laboratory Safety within the Scope of Occupational Health and Biosafety

Occupational health and biosecurity terms include scientific approaches regarding ethical values, reliable methods, and a series of precautions to be taken against risks and hazards for employees and the living material being studied. Research and development activities carried out within the scope of biotechnology involve many risks under laboratory conditions, which are their own physical area. Many precautions and practices have been defined to analyze these risks and take precautions before they occur, and laboratory guides have been created in line with these definitions. During studies carried out with experimental animals under laboratory conditions, safe working rules may be violated due to physical conditions, equipment and materials, treatments applied to the subjects, negligence, or faulty practices caused by the researcher or expert. Biosafety in animal experiments consists of a set of ethical conditions and practices declared in the guidelines of specialized laboratories at their own level, protecting employees, subjects, and life outside the laboratory. In this review, possible risks and dangers that may arise at different biosafety levels and the precautions and practices that can be taken against them are evaluated. In this way, it was aimed to contribute to the development of laboratory and biosafety criteria in animal experiments.

Impact of an objective scoring system on initiation of therapy in patients with International Neuroblastoma Risk Group Staging System (INRGSS) stage MS neuroblastoma: A report from the Children’s Oncology Group.

10003 Background: A subset of children with INRGSS Stage MS neuroblastoma (NBL) may be observed without treatment, while others have rapidly evolving symptoms that can be life-threatening. ANBL1232 adapted a previously developed semi-quantitative objective scoring system (OSS) to assign a numeric value to symptoms and laboratory abnormalities. The goal was to standardize monitoring, therapy initiation, and treatment duration in this cohort. Methods: Patients with newly diagnosed Stage MS NBL were eligible for this prospective trial. An OSS score (OSSS) was assigned at enrollment; the total number was based on scoring in 5 systems: gastrointestinal (GI), respiratory, circulatory, renal, and hepatic. Within the 5 systems, individual clinical and laboratory parameters were scored as not present = 0, mild/moderate = 1 [Grade 2 CTCAEv4.0 adverse event (AE)] or severe = 2 (Grade ≥3 AE). The OSSS was the sum of highest score within each organ system (maximum score: 2 per system, 10 total). Asymptomatic MS patients with an OSSS &lt; 2 who were either &lt; 3 months (mo) of age without hepatomegaly or 3-18 mo of age with favorable biology tumors were eligible for observation without initial treatment. Observed patients underwent monthly physical examinations and laboratory assessments for the first 6 mo following diagnosis. Tumor imaging was performed every 3 mo for 1 year, then every 6-12 mo through 36 mo. An OSSS ≥2 or a protocol-defined increase in primary tumor size prompted initiation of therapy. Results: From July 2014 to February 2021, 89 eligible and evaluable patients with newly diagnosed stage MS NBL enrolled. Among these, 18 (20.2%; 5 male and 13 female) were eligible for observation. Observed patients were older at diagnosis (median age: 2.87 vs. 1.81 mo, p = 0.23) and more likely to have primary tumors without image-defined risk factors (62.5% vs. 30.0%, p = 0.0166) than those assigned to therapy up front. Nearly all observed patients (17/18) had abdominal/adrenal primaries. The initial OSSS was 0 in all observed patients. Median reported observation time was 36 mo (range: 1-36 mo); 13 patients completed all required monthly assessments for the first 6 mo. No patients in the observation cohort required initiation of therapy for an increase in OSSS. One patient with OSSS = 1 at mo 3 had complete GI symptom resolution by mo 5. Conclusions: An OSSS of 0 at diagnosis can aid in identifying a favorable group of patients with stage MS NBL who can be safely observed. No patients in the observation cohort developed evidence of organ dysfunction or OSSS &gt; 1 despite frequent physical examination and comprehensive laboratory testing, suggesting that follow up may be safely liberalized in this population over time. Clinical and laboratory criteria implemented at diagnosis could be used to identify patients requiring prompt treatment. Clinical trial information: NCT02176967 .

Coagulase-negative Staphylococci – A True Pathogen in Bloodstream Infections and their Resistance Patterns in a Tertiary Care Hospital

Coagulase-negative staphylococci (CoNS) are primary skin commensals that have long been considered contaminants even when grown in blood cultures. This group of organisms has been recently recognized as a potential causative pathogen of septicemia. This increase has been attributed to the increased use of intravascular and prosthetic devices. Hence, we aimed to estimate the prevalence of CoNS as a true pathogen in adult and pediatric blood cultures along with their antibiotic susceptibility patterns. A total of 1076 adult and 611 pediatric blood cultures were subjected to an automated BacT/ALERT continuous monitoring system. Isolated CoNS were considered true pathogens if they met the diagnostic, clinical, and laboratory criteria. Antimicrobial susceptibility testing for pathogenic CoNS was carried out using the Kirby-Bauer disk diffusion method and interpreted as per CLSI 2021. CoNS were considered true pathogens in 23 (42.5%) of 54 adults and 12 (41.3%) of 29 pediatric CoNS isolated from blood cultures. Methicillin-resistant CoNS was detected in 66% and 70% of adult and pediatric cultures, respectively. All the CoNS isolates were sensitive to vancomycin and linezolid. Coagulase-negative staphylococci (CoNS) can either be a contaminant or a true pathogen, whose discrimination based on clinical and laboratory indices plays a pivotal role in the management of patients with sepsis.

#2859 Clinical and morphological characteristics of biopsy-proven kidney graft rejection in Latvia

Abstract Background and Aims Kidney transplantation is a treatment for many patients with end stage renal disease leading to increased quality of life. In last decades results in kidney transplantation have been improving, but allograft rejection remains an important clinical problem. Graft biopsy remains the gold standard to assess the cause of kidney transplant status. This study aimed to determine clinical and histopathological characteristics, treatment and short-term outcomes of biopsy-proved kidney graft rejection in Latvia. Method In this retrospective observational study all kidney allograft biopsies performed in Pauls Stradins Clinical University Hospital from January 2014 till December 2022 was reviewed. Biopsies with rejection, ≥7 glomeruli, patients ≥18 years old were included. Acute rejection was diagnosed according to clinical, laboratory and biopsy-proven acute rejection (BPAR) histological criteria. BPAR was classified and subdivided using Banff criteria. All recipients universally received either depleting or non-depleting induction therapy. Most of the patient (82%) for maintenance immunosuppression (MI) received triple therapy with calcineurin inhibitor, mycophenolate mofetil, and prednisone, others—in different combinations with above and mammalian target of rapamycin (mTOR), azathioprine. Graft function was evaluated according to glomerular filtration rate (GFR), calculated with the CKD-EPI Creatinine, 2021 equation. Treatment strategies, laboratory data at the time of biopsy and after 1 year follow-up were analysed. Repeated-control biopsies after receiving therapy were excluded. Data were analysed using descriptive statistics and T-test. Results From all 523 biopsies, further included and analysed were 153 (total 146 patients). 58% were males, average patient age was 45.5 years. Most 84% of the grafts were from deceased, 8%—living donors. Mean time from transplantation to biopsy was 32 months. Acute antibody-mediated rejection (AAMR) was diagnosed in 41% cases, chronic-active antibody mediated (CAAMR)—25%, followed by mixed 16%, acute cellular (ACR) 10% and borderline 8% rejection. Besides augmented MI for almost all patients, pulse steroids (GCS) were the most commonly 70% administered treatment, followed by plasma exchange 59% (PEX), rituximab (RTX) 50%, immunoglobulins (IG) 24% and anti-thymocyte globulin (ATG) 10% in different, mostly non-homogenous combinations. Non adherence, advanced fibrotic changes in biopsy and serious comorbidities were the main reasons patients did not receive specific treatment besides intensified MI. The most favourable outcomes were in ACR where mean allograft GFR increased +20.7 ml/min after one year, compared to the worst outcome CAAMR group where GFR decreased −4.7 ml/min (p = 0.03). In ACR group 92% graft function stayed the same or improved, moreover 54% graft function increased ≥20% from baseline; similarly in mixed and AAMR group GFR increase ≥20% were for 45% and 48%, compared to CAAMR where it was only for 6% of patient. Furthermore, the CAAMR group was with the most patients (48%) who returned to dialysis or died. In AAMR and mixed rejection groups mean GFR changes were close +13.4 ml/min and +12.9 ml/min (p = 0.95). There were no statistically significant associations between treatment outcomes in PEX+RTX+GCS vs PEX+RTX+GCS+IG in the AAMR group (p = 0.382). Overall, 3.9% of patients died. Conclusion Overall BPAR prevalence between kidney graft biopsies was high (29%). Antibody mediated rejection was diagnosed most often with least favourable short-term outcomes in CAAMR group. Despite various improvements in immunosuppression, CAAMR remains a serious cause of transplant dysfunction or loss.

Analysis of the clinical diagnostic capabilities of kidney imaging biomarkers based on diffusion-weighted imaging and ASL-perfusion data

Acute kidney failure is a polyetiological disease that is often occurs in patients, which requires a rapid therapeutic response to avoid progression of the condition. Magnetic resonance imaging of the kidneys (MRI) improves the understanding and assessment of pathological processes, supplementing the mandatory diagnostic minimum information in the study of kidney pathology.Objective. To evaluate the clinical diagnostic capabilities of kidney imaging biomarkers using diffusion-weighted imaging (DWI) and ASL-perfusion data for intensive care unit patients.Materials and methods. At the first Clinical Hospital in Smolensk 54 patients were examined who were inpatient treatment and in the intensive care unit. All patients underwent ultrasound examination of the kidneys with assessment of blood flow in the main kidney vessels, MRI of the kidneys, with DWI of the kidney parenchyma and ASL-perfusion included in the study protocol. MRI was carried with assessed b-factor 800 and was drawn apparent diffusion coefficient (ADC) maps. When carried ASL perfusion, the field of view covered the area of the parenchyma of both kidneys. The reference method was glomerular filtration rate for all of the patients. The control group was represented by healthy people (n=59). Consent to participate in the study was obtained from patients or their legal representatives. All stages of the study comply with the normative and regulatory documentation of Ministry of Health ща the Russian Federation.Results. It was concluded that there is a significant difference in ADC for prerenal causes and in ASL for renal causes. In 9 (16.7 %) patients, kidney ADC was 1.5±0.3 mm2/sec, ASL – perfusion – ≤ 250 ml/100g/min, compared with the control group. In this group, negative dynamics were observed within a week, тnegative laboratory dynamics correlates with radiation-based kidney biomarkers (r=0,965).Conclusion. The criteria of DWI and ASL-perfusion allow us to suspect or confirm the cause of acute kidney failure. A high correlation has been established between radiation biomarkers and laboratory criteria of functional damages (r=0.998), direct correlation between imaging biomarkers and organic kidney disease (r=0,901). These biomarkers make it possible to predict the first stage of acute kidney failure (AUROC 0,995, DI 0,867–0,999).

Metformin-Associated Lactic Acidosis: Which Elimination Therapy to Use in Case of Haemodynamic Instability? A Retrospective Cohort Study

Introduction: Metformin, a commonly used oral antihyperglycemic drug, poses a rare risk related to the development of metformin-associated lactic acidosis (MALA). The Extracorporeal Treatments in Poisoning (EXTRIP) group recommended intermittent haemodialysis (IHD) as a primary elimination therapy in case of severe metformin poisoning. However, in haemodynamically unstable patients, our previous observations suggested that continuous venovenous haemofiltration (CVVH) might be more effective. This retrospective cohort study aimed to contribute evidence on the use of IHD and CVVH in patients with severe MALA, particularly in haemodynamically unstable patients. Methods: Data from January 2015 to December 2020 were collected from the Leuven University Hospital. Two separate search methods, based on hospital activity records and laboratory criteria, were used to identify patients with MALA. Patients diagnosed with MALA, receiving extracorporeal treatment within 24 h of admission, were included. Patients were categorized into the IHD and CVVH groups. Patient characteristics, treatment details, and outcomes were analysed. Results: Among 358,148 patient records, 35 MALA cases were identified. IHD was chosen as the initial elimination technique in 13 cases, whereas 22 patients were first commenced on CVVH. Patients treated with CVVH were sicker, had more comorbidities and had higher ventilation and vasopressor requirements. CVVH group had longer vasopressor use, longer ICU stays, and higher in-hospital mortality. Discussion: CVVH rather than IHD seems to be the preferred elimination technique in the more critically ill patients with MALA. Due to its retrospective design, this study failed to identify the superior elimination technique in terms of efficacy. Poorer outcomes in the CVVH group are likely attributed to the severity of illness rather than the inferiority of the elimination therapy. We acknowledge the diagnostic challenges regarding MALA. Using metformin assays could be beneficial in managing these patients. Conclusions: This study suggests clinicians’ preference for CVVH in severe cases of MALA with haemodynamic instability.

Hepatic Dysfunction Quantified by HepQuant DuO Outperforms Child-Pugh Classification in Predicting the Pharmacokinetics of Ampreloxetine.

HepQuant tests quantify liver function from clearance of deuterium- and 13C-labeled cholates administered either intravenously and orally (SHUNT) or orally (DuO). Hepatic impairment studies have relied on clinical or laboratory criteria like Child-Pugh classification to categorize the degree of hepatic dysfunction. We compared HepQuant tests with Child-Pugh classification in predicting the pharmacokinetics of ampreloxetine. Twenty-one subjects with hepatic impairment (8 Child-Pugh A, 7 Child-Pugh B, and 6 Child-Pugh C), and 10 age- and sex-matched controls were studied. The pharmacokinetics of ampreloxetine were measured after oral administration of a single dose of 10 mg. Disease severity index (DSI), portal-systemic shunting (SHUNT%), hepatic reserve, and hepatic filtration rates (HFRs) were measured from serum samples obtained after intravenous administration of [24-13C]-cholate and oral administration of [2,2,4,4-2H]cholate. Ampreloxetine plasma exposure (AUC0-inf) was similar to controls in Child-Pugh A, increased 1.7-fold in subjects with Child-Pugh B, and 2.5-fold in subjects with Child-Pugh C and correlated with both Child-Pugh score and HepQuant parameters. The variability observed in ampreloxetine exposure (AUC0-inf) in subjects with moderate (Child-Pugh B) and severe hepatic impairment (Child-Pugh C) was explained by HepQuant parameters. Multivariable regression models demonstrated that DSI, SHUNT%, and Hepatic Reserve from SHUNT and DuO were superior predictors of ampreloxetine exposure (AUC0-inf) compared to Child-Pugh score. HepQuant DSI, SHUNT%, and hepatic reserve were more useful predictors of drug exposure than Child-Pugh class for ampreloxetine and thus may better optimize dose recommendations in patients with liver disease. The simple-to-administer, oral-only DuO version of the HepQuant test could enhance clinical utility.

Gonorrhoea in Poland in 2021.

The incidence of gonorrhoea at the European level increased over 2012-2019, decreased in 2020, and then reached higher values in 2021 than in 2019. Analysis in the descriptive epidemiology scheme of gonorrhoea notification in surveillance in Poland in 2021 (being the second year of the COVID-19 pandemic). Case-base data from surveillance of gonorrhoea were used: confirmed case (meeting laboratory criteria), probable (meeting clinical criteria and contact with confirmed case) and possible (only in Poland - physician diagnosed gonorrhoea, no information available for proper classification). Statistic Poland data was used to calculate the indicators. Data on patients treated in dermatology-venereology clinics between 2019-2021 were taken from the Bulletins of the Ministry of Health. The incidence of gonorrhoea in Poland in 2021 was only a fraction of recorded in the EU/EEA (0.74 vs. 13.7/100000)-similar to the first pandemic year and were about half of those notified in the 2019 (the peak year; 281 vs. 522 cases). There were 15.5 men per one female (incidence: 1.6/100000 men, 0.1/100000 women). Every second case was among aged 25-34 (49.62%), every fourth-aged 35-44 (23.11%). Under 15, no cases were reported. The predominant site was the genitourinary (excluding missing data: 85.3%). The cases with missing information on transmision increased (49.1%; aged 45+: 72.0%, women: 76.5%). Delays in reporting data were identified (greater than in 2019, however, less than in 2020), ~17% cases were from 2019-2020. Dermatology-venerology clinics treated 385 people - less than in 2020, however, more than reported in epidemiological surveillance (vs. 281). The COVID-19 pandemic has influenced on the surveillance system in Poland. There are difficulties in interpreting the epidemiological trend. It is necessary to: 1) intensify systemic solutions in the area of prevention, including sexual partners; 2) raise the awareness of healthcare professionals and sanitary inspection workers on the role of collecting epidemiological information.

Screening for familial hypercholesterolemia in Sri Lanka: A laboratory-based multicenter study

Background: Familial hypercholesterolemia (FH) is a genetic lipid disorder characterized by increased concentrations of low-density lipoprotein cholesterol (LDL-C) in the circulatory system, resulting in a markedly increased vulnerability in the development of atherosclerotic cardiovascular disease at an early age. The prevalence of FH in a Sri Lankan setting was identified in a tertiary hospital laboratory and a primary care family practice laboratory by performing opportunistic screening for index cases using laboratory criteria as a starting point. Methodology: This study assessed the prevalence of FH using the Dutch Lipid Clinic Network (DLCN) Criteria score. The evaluation was conducted over 6 months in both a tertiary hospital laboratory and a primary care laboratory. Once patients were identified by high LDL, the patients were recruited to the study and assessed clinically. Secondary causes were excluded, and clinical evaluations of the patients were done to see if they had clinical features of FH. Results: Of the total of 3039 serum lipid profiles that were reviewed, there were 42 (1.38%) lost to follow-up. There were 72 samples with high LDL (190 mg/dL) ≥4.9 mmol/L (190 mg/dL). Of the patients with LDL &gt;4.9 mmol/L, 16 (0.52%) cases with identified secondary causes (untreated hypothyroidism [n = 13], nephrotic syndrome [n = 3], and no secondary investigations [n = 14]) were excluded. In total, the point prevalence of likely phenotypical FH based on DLCN (probable or confirmed) and an LDL-C &gt;4.9 mmol/L was calculated as approximately 14/3039 (1:217). Conclusions: The point prevalence of FH in patients undergoing lipid profile testing in a tertiary hospital laboratory and a primary care laboratory was 1:217 which is comparable with the prevalence of FH in the general population in the world (based on 1 in 200–250). Based on the laboratory criteria, initiating screening for FH in resource-limited settings could be an effective screening strategy to identify patients with FH. Until national screening programs are established, the laboratory as an avenue to trigger screening for FH is useful in lower-middle-income countries like Sri Lanka.

Role of endoplasmic reticulum aminopeptidase-1 gene polymorphism (rs13167972) in occurrence susceptibility of ankylosing spondylitis in a sample of Iraqi male patients.

Ankylosing spondylitis (AS) is a chronic and systemic seronegative inflammatory spondyloarthropathy, an autoimmune disease that has been associated with impaired Endoplasmic Reticulum Aminopeptidase (ERAP)-1 activity, which is involved in priming antigenic peptides. The purpose of this study is to investigate the association of 3-UTR of ERAP1 gene polymorphism (rs13167972) with the AS occurrence susceptibility in a sample of Iraqi male patients. The AS patients were diagnosed clinically and by magnetic resonance imaging (MRI) and other clinical and laboratory criteria like symptoms, increased C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). The blood grouping and Body Mass Index (BMI) were also investigated to be associated with AS occurrence. The genotyping of the 3-UTR region of the ERAP1 gene (rs13167972) was done by Sanger sequencing. The results revealed that the AS occurred significantly in the age group of 20-35years (p = 0.013). The BMI shows that the AS patients were overweighted males (p = 0.013) and the most predominant blood group in AS patients was O- (p = 0.002). The ESR and serum level of CRP were significantly raised in AS patient sera (< 0.001). The results of the receiver-operating characteristics curve analysis (ROC) revealed that the CRP (AUC: 0.995, cut-off: 2.48mg/L, had 95% %sensitivity, 100% specificity, p < 0.001) is more discriminative than BMI (AUC: 0.300, cut-off: 46.91kg, had 0% sensitivity, 100% specificity, p = 0.001), and ESR (AUC: 0.808, cut-off: 7.50mm/hr, had 60% sensitivity, 88% specificity, p < 0.001) in distinguishing between AS patients and control group. The genotyping of the 3-UTR region of ERAP1 gene (rs13167972) result shows that the AG and GG genotypes are significantly occurring in AS patients (70%, OR: 2.33, 95%CI: 1.02-5.36, p = 0.04). The G allele is significantly occurring in AS patients (47%, OR: 2.07, 95CI%: 1.15-3.71, p = 0.01). The AS occurred in young overweight males with blood group O-. The AG and GG genotypes are risk factors for AS development while the G allele is a risk factor that increases the chances for disease incidence.

Insight into antiphospholipid syndrome: the role and clinical utility of neutrophils extracellular traps formation

Antiphospholipid syndrome (APLS) is a systemic immune dysregulation distinguished by repetitive complications and pregnancy loss in the absence of definite etiology. Most research focuses on the laboratory detection and clinical features of APLS, but its precise etiology remains to be deeply explored. NETosis is a newly developed theory in the pathophysiology of APLS which may serve as the missing bridge between coagulation and inflammation reaching the disease progression and severity. We aimed in this study to navigate the prognostic role of NETosis in thrombotic APLS. Our study included 49 newly diagnosed APLS patients (both 1ry and 2ry) who met clinical and laboratory criteria as per the international consensus statement on the update of the classification criteria for definite APLS and were sub-classified according to the occurrence of thrombotic events in thrombotic and non-thrombotic types. In addition, 20 sex and age-matched reactive subjects and 20 sex and age-matched healthy volunteer controls were enrolled. NETosis formation was assessed by measuring serum Myeloperoxidase (MPO) and Histones level using the enzyme-linked immunosorbent assay (ELISA) technique. Both MPO and Histones levels were able to discriminate among APLS cases from normal controls, showing significant cutoffs of > 2.09 ng/ml for MPO and > 1.45 ng/ml for Histones (AUC values were 0.987and 1.000, respectively). These values can be used as predictors for NETosis pathophysiology in APLS patients. Additionally, these markers demonstrated a significant association with several prognostic indicators, including thrombosis, higher PT and INR, and lower hemoglobin (Hb) levels which are supposed to be ameliorated by using NETs inhibitors. In conclusion, we suggest that measuring NETosis markers, MPO, and Histones, in the early course of APLS using proposed cutoff values will facilitate the timely initiation of anti-NETosis therapy and improve the overall prognosis, particularly for patients with thrombotic APLS.

Serum fibroblast growth factor 19 level correlates inversely with clinical and endoscopic activity of inflammatory bowel disease.

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), is a chronic condition with relapsing-remitting course. Diarrhea and abdominal pain are the most common IBD symptoms. Fibroblast growth factor 19 (FGF19) is an endocrine factor that inhibits hepatic bile acid production and may be used as a diagnostic marker for bile acid malabsorption. To assess serum FGF19 levels in active and inactive phases of IBD and find a potential correlation between FGF19 and disease activity. Fasting serum FGF19 levels were measured in 105 IBD patients (47 UC patients, 41 CD patients without previous ileocecal resection (NR-CD), 17 CD patients after ileocecal resection (IR-CD), and 17 control subjects). The disease activity was assessed using clinical, laboratory and endoscopic criteria. Inverse correlations were found between FGF19 level and intensity of diarrhea (in UC), abdominal pain intensity (in UC and IR-CD) and inflammatory markers (in UC and IR-CD). Moreover, FGF19 concentration was inversely correlated with clinical and endoscopic activity indices in UC and CD. Fluctuations in FGF19 level related to clinical and endoscopic activity of UC and CD revealed a clear pattern of higher values in remission than in active disease phases. Fibroblast growth factor 19 may serve as a potential diagnostic biomarker and constitute a new therapeutic target in IBD.

Real-World Experience with 177Lu-PSMA-617 Radioligand Therapy After Food and Drug Administration Approval.

We report our initial real-world experience with 177Lu-PSMA-617 radioligand therapy. Methods: We performed a retrospective review of patients treated with 177Lu-PSMA-617. Pretreatment PSMA PET, laboratory findings, overall survival, a fall in prostate-specific antigen by 50% (PSA50), and toxicities were evaluated. Results: Ninety-nine patients were included. Sixty patients achieved a PSA50. Seven of 18 (39%) patients who did not meet the TheraP PSMA imaging criteria achieved a PSA50. Nineteen of 31 (61%) patients who did not meet the VISION laboratory criteria achieved a PSA50. Sixty-three patients had a delay or stoppage in therapy, which was due to a good response in 19 patients and progressive disease in 14 patients. Of 10 patients with a good response who restarted treatment, 9 subsequently achieved a PSA50 on retreatment. The most common toxicities were anemia (33%) and thrombocytopenia (21%). Conclusion: At our center, patients who did not meet the TheraP PSMA imaging criteria or the VISION laboratory criteria benefited from 177Lu-PSMA-617 radioligand therapy.

Geochemical processes, salinity sources and utility characterization of groundwater in a semi-arid region of Iraq through geostatistical and isotopic techniques.

Identifying factors contributing to water salinity is paramount in efficiently managing limited water resources in arid environments. The primary objective of this study is to enhance understanding regarding the hydrochemistry, source, and mechanism of water salinity, as well as to assess the suitability of water for various uses in southern Iraq. The groundwater samples were collected from water wells and springs and analyzed for major cations and anions along with stable isotopes (δ18O and δ2H) to accomplish the objective. The analysis of major ion chemistry, hydrochemical techniques, principal component analysis (PCA), and isotope signatures were adopted to determine the primary factors contributing to water mineralization. The study inferred that evaporation and geological processes encompassing water-rock interactions, such as dissolution precipitation and ion exchange, were key processes. The stable isotope analysis revealed that the water originated from meteoric sources and underwent significant evaporation during or before infiltration. The utility assessment of water samples indicates that most samples are not appropriate for consumption and are significantly below the established standards for potable water. In contrast, a significant portion of the groundwater samples were found to meet the criteria for irrigation suitability by adopting Wilcox and the US Salinity Laboratory criteria. The groundwater could be considered for irrigation with proper salinity control management. Overall, this study has significantly improved the understanding of the hydrogeochemical regimes and acts as a first step toward the sustainable utilization of water resources.

Performance validation of the 2023 American College of Rheumatology/European League Against Rheumatism antiphospholipid syndrome classification criteria in an antiphospholipid syndrome cohort

BackgroundThe 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) antiphospholipid syndrome (APS) classification criteria were developed with higher specificity but lower sensitivity compared with the 2006 Sydney revised classification criteria. ObjectivesTo validate the performance of the 2023 ACR/EULAR APS classification criteria in a large Chinese APS cohort. MethodsThis was a single-center cohort study. Inclusion criteria aligned with the entry criteria of 2023 criteria. APS classification by “expert consensus panel” served as the gold standard. Sensitivity and specificity were compared between the 2023 and 2006 criteria. ResultsA total of 526 patients with a mean age of 38.55 ± 12.67 years were enrolled, of whom 366 (69.58%) were female and 182 (34.60%) had systemic lupus erythematosus (SLE). Among them, 407 (77.38%) patients were classified as APS by experts. The 2023 criteria demonstrated higher overall specificity than the 2006 criteria (0.983 vs 0.950), while sensitivity was relatively lower (0.818 vs 0.853). The sensitivity of the 2023 criteria improved for patients with SLE (0.860 vs 0.825), microvascular manifestations (0.867 vs 0.786), cardiac valve disease (0.903 vs 0.774), and thrombocytopenia (0.811 vs 0.790). Reduced sensitivity of the 2023 criteria was linked to the omission of certain microvascular manifestations, a stricter definition of pregnancy morbidity, and the exclusion of isolated thrombocytopenia and isolated IgM isotype antiphospholipid antibodies from meeting clinical and laboratory criteria, respectively. ConclusionThe 2023 criteria offer higher overall specificity and improved sensitivity in specific patient subsets, such as those with SLE, microvascular manifestations, cardiac valve disease, and thrombocytopenia when compared with the 2006 criteria.

Investigating the association between the tissue expression of miRNA-101, JAK2/STAT3 with TNF-α, IL-6, IL-1β, and IL-10 cytokines in the ulcerative colitis patients.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by numerous factors, such as immune system dysfunction and genetic factors. MicroRNAs (miRNAs) play a crucial role in UC pathogenesis, particularly via the JAK-STAT pathway. Our aim was to investigate the association between miRNA-101 and JAK2-STAT3 signaling pathway with inflammatory cytokines in UC patients. We enrolled 35 UC patients and 35 healthy individuals as the control group, referred to Shariati Hospital, Tehran, Iran. Patients were diagnosed based on clinical, laboratory, histological, and colonoscopy criteria. RNA and protein extracted from tissue samples. Real-time PCR was used to assess the expression levels of miRNA-101, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-10 genes, while western blot was employed to measure levels of P-STAT3, total STAT3, and JAK2 proteins. Expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 significantly increased, while the expression of IL-10 significantly decreased in the case group versus controls. Additionally, miRNA-101 expression was significantly higher in UC patients. A significant correlation between miRNA-101 and IL-6 expression was observed, indicating their relationship and possible impact on cell signaling pathways, JAK2-STAT3. No significant changes were observed in phosphorylated and total STAT3 and JAK2 protein expression. This study provides evidence of increased miRNA-101 expression in UC tissue, suggesting a potential correlation between miRNA-101 and IL-6 expression and their involvement in the JAK2-STAT3 pathway. The study confirms alterations in UC patients' pro-inflammatory cytokines and anti-inflammatory IL-10. However, further investigations are needed to understand the exact role of miRNA-101 in UC pathogenesis fully.