The feasibility of soluble Fms-Like Tyrosine kinase-1 (sFLT-1) and Placental Growth Factor (PlGF) ratio biomarker in predicting preeclampsia and adverse pregnancy outcomes among medium to high risk mothers in Kuala Lumpur, Malaysia.

BACKGROUND: Preeclampsia significantly contributes to maternal and perinatal morbidity and mortality. It is imperative to identify women at risk of developing preeclampsia in the effort to prevent adverse pregnancy outcomes through early intervention. Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) level changes are noticeable several weeks before the onset of preeclampsia and its related complications. This study evaluated the feasibility of the sFlt-1/PlGF biomarker ratio in predicting preeclampsia and adverse pregnancy outcomes using a single cut-off point of >38. METHODS: This is a prospective cohort study conducted at a single tertiary centre, in an urban setting in Kuala Lumpur, Malaysia, between December 2019 and April 2021. A total of 140 medium to high risk mothers with singleton pregnancies were recruited at ≥20 weeks' gestation. sFlt-1/PlGF ratio was measured and the participant monitored according to a research algorithm until delivery. The primary outcome measure was incidence of preeclampsia and the secondary outcome measure was incidence of other adverse pregnancy outcomes. RESULTS: The overall incidence of preeclampsia was 20.7% (29/140). The mean sFlt-1/PlGF ratio was significantly higher in preeclampsia (73.58 ± 93.49) compared to no preeclampsia (13.41 ± 21.63) (p = 0.002). The risk of preeclampsia (adjusted OR 28.996; 95% CI 7.920-106.164; p<0.001) and low Apgar score (adjusted OR 17.387; 95% CI 3.069-98.517; p = 0.028) were significantly higher among women with sFlt-1/PlGF ratio >38 compared with sFLT-1/PlGF ratio ≤38. The area under the receiver-operator characteristic curve (AUC) for a combined approach (maternal clinical characteristics and biomarker) was 86.9% (p<0.001, 95% CI 78.7-95.0) compared with AUC biomarker alone, which was 74.8% (p<0.001, 95% CI 63.3-86.3) in predicting preeclampsia. The test sensitivity(SEN) was 58.6%, specificity (SPEC) 91%,positive predictive value (PPV) 63% and negative predictive value (NPV) 89.3% for prediction of preeclampsia. For predicting a low Apgar score at 5 minutes, the SEN was 84.6%, SPEC 87.4%, PPV 40.7%, and NPV 98.2%; low birth weight with SEN 52.6%,SPEC 86.0%, PPV 37.0%, NPV 92.0%; premature delivery with SEN 48.5%, SPEC 89.5%, PPV 59.3%, NPV 84.7% and NICU admission with SEN 50.0%, SPEC 85.8%, PPV 37.0% and NPV 91.2%. CONCLUSIONS: It is feasible to use single cut-off point of >38 ratio of the biomarkers sFlt-1/PlGF in combination with other parameters (maternal clinical characteristics) in predicting preeclampsia and adverse pregnancy outcomes among medium to high risk mothers without restricting outcome measurement period to 1 and 4 weeks in a single urban tertiary centre in Kuala Lumpur, Malaysia.

Comparison of sPLA2IIA performance with high-sensitive CRP neutrophil percentage PCT and lactate to identify bacterial infection.

Early bacterial infection (BI) identification in resource-limiting Emergency Departments (ED) is challenging, especially in low- and middle-income counties (LMIC). Misdiagnosis predisposes to antibiotic overuse and propagates antimicrobial resistance. This study evaluates new emerging biomarkers, secretory phospholipase A2 group IIA (sPLA2-IIA) and compares with other biomarkers on their performance characteristic of BI detection in Malaysia, an LMIC. A prospective cohort study was conducted involving 151 consecutive patients admitted to the ED. A single measurement was taken upon patient arrival in ED and was analysed for serum levels of sPLA2-IIA, high-sensitive C-reactive protein (CRP), procalcitonin (PCT), neutrophil percentage (N%), and lactate. All biomarkers' performance was compared for the outcomes using area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity. The performance of sPLA2-IIA (AUROC 0.93 [95% CI: 0.89-0.97]; Sn 80% [95% CI: 72-87]; Sp 94% [95% CI: 81-89]) was the highest among all. It was comparable with high-sensitive CRP (AUROC 0.93 [95% CI: 0.88-0.97]; Sn 75% [95% CI: 66-83]; Sp 91 [95% CI: 77-98]) but had a higher Sn and Sp. The sPLA2-IIA was also found superior to N%, PCT, and lactate. This finding suggested sPLA2-IIA was recommended biomarkers for BI detection in LMIC.

An Amperometric Biosensor for the Determination of Bacterial Sepsis Biomarker, Secretory Phospholipase Group 2-IIA Using a Tri-Enzyme System.

A tri-enzyme system consisting of choline kinase/choline oxidase/horseradish peroxidase was used in the rapid and specific determination of the biomarker for bacterial sepsis infection, secretory phospholipase Group 2-IIA (sPLA2-IIA). These enzymes were individually immobilized onto the acrylic microspheres via succinimide groups for the preparation of an electrochemical biosensor. The reaction of sPLA2-IIA with its substrate initiated a cascading enzymatic reaction in the tri-enzyme system that led to the final production of hydrogen peroxide, which presence was indicated by the redox characteristics of potassium ferricyanide, K3Fe(CN)6. An amperometric biosensor based on enzyme conjugated acrylic microspheres and gold nanoparticles composite coated onto a carbon-paste screen printed electrode (SPE) was fabricated and the current measurement was performed at a low potential of 0.20 V. This enzymatic biosensor gave a linear range 0.01-100 ng/mL (R² = 0.98304) with a detection limit recorded at 5 × 10-3 ng/mL towards sPLA2-IIA. Moreover, the biosensor showed good reproducibility (relative standard deviation (RSD) of 3.04% (n = 5). The biosensor response was reliable up to 25 days of storage at 4 °C. Analysis of human serum samples for sPLA2-IIA indicated that the biosensor has potential for rapid bacterial sepsis diagnosis in hospital emergency department.

Serum Procalcitonin Predicts Anastomotic Leaks in Colorectal Surgery

Background: Anastomotic leaks in colorectal surgery results in a high morbidity and mortality rate. Serum procalcitonin levels is known as a sensitive and specific marker of sepsis and could be use as a marker for early detection of a leak allowing early intervention. It may help a clinician decide to perform a CT scan even earlier especially when the diagnosis of a leak is uncertain. The aim of this study is to determine whether serum procalcitonin is a good predictor of anastomotic leak in colorectal surgery. Methodology: Between July 2014 until October 2015, 70 patients undergoing colorectal surgery were prospectively analyzed in a single-center tertiary teaching hospital. Demographic and surgical data were obtained. Serum procalcitonin was taken before surgery and at day 3 (72 hours) postoperatively. During the postoperative period, the patients were observed in the ward for features of anastomotic leak and if present, it was managed accordingly. The primary outcome was to prospectively determine an association between serum procalcitonin levels and an anastomotic leak in patients who underwent colorectal surgery with a primary anastomosis. Result: The rate of anastomotic leak was 4.5% (3 patients) with a mortality rate of 4.3% (3 patients). A rise in serum procalcitonin was statistically significant among patients with anastomotic leak. The optimal procalcitonin cut-off level at postoperative day 3 was 5.27 ng/mL, resulting in 100% sensitivity, 85% specificity, 23% positive predictive value and 100% negative predictive value. Nevertheless, none of the variables showed statistical significance with an anastomotic leak. Conclusion: Procalcitonin is a reliable biochemical marker to help diagnose anastomotic leak in colorectal surgery. Our study has shown that a level of 5 times beyond normal is statistically significant and a value of more than 5.27 ng/mL is confirmatory of a leak.

CD64 and Group II Secretory Phospholipase A2 (sPLA2-IIA) as Biomarkers for Distinguishing Adult Sepsis and Bacterial Infections in the Emergency Department.

INTRODUCTION: Early diagnosis of sepsis and bacterial infection is imperative as treatment relies on early antibiotic administration. There is a need to develop new biomarkers to detect patients with sepsis and bacterial infection as early as possible, thereby enabling prompt antibiotic treatment and improving the survival rate. METHODS: Fifty-one adult patients with suspected bacterial sepsis on admission to the Emergency Department (ED) of a teaching hospital were included into the study. All relevant cultures and serology tests were performed. Serum levels for Group II Secretory Phospholipase A2 (sPLA2-IIA) and CD64 were subsequently analyzed. RESULTS AND DISCUSSION: Sepsis was confirmed in 42 patients from a total of 51 recruited subjects. Twenty-one patients had culture-confirmed bacterial infections. Both biomarkers were shown to be good in distinguishing sepsis from non-sepsis groups. CD64 and sPLA2-IIA also demonstrated a strong correlation with early sepsis diagnosis in adults. The area under the curve (AUC) of both Receiver Operating Characteristic curves showed that sPLA2-IIA was better than CD64 (AUC = 0.93, 95% confidence interval (CI) = 0.83-0.97 and AUC = 0.88, 95% CI = 0.82-0.99, respectively). The optimum cutoff value was 2.13µg/l for sPLA2-IIA (sensitivity = 91%, specificity = 78%) and 45 antigen bound cell (abc) for CD64 (sensitivity = 81%, specificity = 89%). In diagnosing bacterial infections, sPLA2-IIA showed superiority over CD64 (AUC = 0.97, 95% CI = 0.85-0.96, and AUC = 0.95, 95% CI = 0.93-1.00, respectively). The optimum cutoff value for bacterial infection was 5.63µg/l for sPLA2-IIA (sensitivity = 94%, specificity = 94%) and 46abc for CD64 (sensitivity = 94%, specificity = 83%). CONCLUSIONS: sPLA2-IIA showed superior performance in sepsis and bacterial infection diagnosis compared to CD64. sPLA2-IIA appears to be an excellent biomarker for sepsis screening and for diagnosing bacterial infections, whereas CD64 could be used for screening bacterial infections. Both biomarkers either alone or in combination with other markers may assist in decision making for early antimicrobial administration. We recommend incorporating sPLA2-IIA and CD64 into the diagnostic algorithm of sepsis in ED.