Multimarker models and risk stratification algorithms for ovarian cancer in women with adnexal masses

Ovarian cancer is the fifth most common cause of cancer-related mortality in women. The main reason is the delayed diagnosis, which limits therapeutic options. There is still no sufficiently reliable screening algorithm for early stratification of high-risk patients and timely referral to specialized oncology centers. There has been ongoing extensive two-decade long research on various protein signatures, multimarker panels, scoring systems, and algorithms combining clinical, biochemical, and imaging data to identify an optimal approach for a sensitive and specific method for early detection of ovarian cancer. This review presents up-to-date information on available multimarker models and discusses their diagnostic sensitivity and specificity for reliable clinical application. It includes data from meta-analyses evaluating the clinical significance of the ROMA algorithm, CPH-I, MMP, OVA1, and OVERA, in comparison with standalone testing of established tumor biomarkers CA125 and HE4

Predictive Role Of Neutrophil Gelatinase-Associated Lipocaline As An Early Marker For Kidney Injury In Patients With Diabetes Mellitus

Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus leading to increased cardiovascular morbidity and mortality, and a risk of developing an end-stage renal disease (ESRD). Diabetic nephropathy is a disease affecting mainly the glomerulus, however, a number of studies indicate the predictive role of tubulo-interstitial lesions in the development and the progression of diabetic nephropathy. Neutrophil gelatinase-associated lipocalin (NGAL) is one of the most promising tubular biomarkers in the diagnosis of kidney disease. The data in the literature determine NGAL as a marker with a good diagnostic profile in the diagnosis of DKD.  Neutrophil gelatinase-associated lipocalin values correlate with the progression of the albumin excretion, with the decrease in the glomerular filtration rate and with the severity of renal impairment.  Neutrophil gelatinase-associated lipocalin is defined as an early marker of DKD, which establishes the development of renal dysfunction before the increase in albumin excretion. The evaluated cut-off values demonstrate good to high efficacy of NGAL in discriminating DKD patients with normal albumin excretion from healthy individuals. Several studies have indicated NGAL as an indicator of DKD progression, stratifying the risk of developing ESRD, patients with diabetes with higher NGAL levels have a faster and earlier decline in renal function. However, NGAL is a modulator of insulin signalling and its levels are elevated in patients with diabetes without DKD. Elevated levels of NGAL may be the result of common concomitant diseases of diabetes—cardiovascular disease and urinary tract infections. Additional studies are needed to assess the clinical applicability of NGAL in the diagnosis of DKD

Screening for acid-labile subunit deficiency in patients with growth hormone deficiency at a tertiary pediatric endocrinology center

Introduction: Acid-labile subunit (ALS) is a glycoprotein, which is produced in the liver in response to growth hormone (GH), with its main role being the formation of a complex with insulin-like growth factor 1 (IGF-1) and IGF-binding-protein-3 (IGFBP-3) in order to extend their circulating half-life and thus support the action of GH. Acid-labile subunit-deficient patients are of research interest because of the unclear incidence of the condition among the short-statured population and the need of specific therapeutic approach.Aim: The aim of this study is to assess the prevalence of ALS deficiency in a cohort of patients with GH deficiency (GHD) followed up in a tertiary university pediatric endocrinology center.Design: The study participants were 71 children (76% boys, age range 2–18 years), diagnosed with GHD by 2 standard GH-stimulation tests (max GH < 10 ng/mL), on GH therapy, and at mean age at the time of collection of samples: 11.6 ± 3.3 years. Blood serum samples were collected from each patient during the routine visits at the center, and then were stored frozen at -80℃ in 0.5 mL aliquots until analysis.Results: Acid-labile subunit deficiency screening identified serum ALS levels with range from 2.2 to 60 mg/L, with a mean of 17.4 ± 8.7 mg/L. The mean ALS levels were significantly lower than the published ones from subjects without short stature but close to the levels in the referred for GHD patients (6.5 ± 4.8 mg/L). Very low ALS levels (< 4.0 mg/L) were detected in 3 (4.2%) of the patients. The low ALS levels corresponded with low SDSheight (-2.8 ± 1.2) and low SDSIGF-1 (-1.4 ± 1.0) before therapy. In one of the 3 patients, the ALS level (2.2 mg/L) was close to that in patients with IGFALS gene mutations (< 1.0 mg/L).Conclusion: The present results show the prevalence of ALS deficiency in the current GH treated cohort and support the evidence that investigation of ALS levels could be helpful in the differential diagnosis of growth disorders

Predictive Role of NGAL – Neutrophil Gelatinase-Associated Lipocalin as an Early Marker for Renal Injury in Patients with Diabetes Mellitus Type 1 And Type 2 // Предиктивна роля на NGAL – неутрофил гелатиназа асоцииран липокалин като ранен маркер за бъбречно увреждане при пациенти със ЗД тип 1 и ЗД тип 2

This thesis examines the role of Neutrophil gelatinase-associated lipocalin (NGAL) as a marker for kidney injury in patients with diabetes mellitus (DM). Significant contributions are the determined age-, and gender-specific reference intervals of pNGAL, uNGAL and uNGAL / uCreatinine (UNC) for the Bulgarian population, measured by immunoturbidimetric analysis, as well as the established biological variation of markers in the reference group. The statistical analysis showed good diagnostic reliability and clinical applicability of pNGAL, uNGAL and UNC in the diagnostics of diabetic kidney disease (DKD) in patients with DM I and DM II. The association of NGAL with markers of kidney injury has been evaluated. The prognostic role of NGAL as a marker for diagnosing DKD in patients with DM I and II have been determined. Cut-off values were established and can be applied in routine practice. The prognostic role of NGAL as a marker for the prognosis of DКD in patients with DM I and DM II was evaluated, and the correlation of NGAL with the markers for metabolic and glycemic control were determined. Dependence in uNGAL and UNC values on urinary tract infections and leukocyturia were found.Дисертационният труд разглежда ролята на Неутрофил гелатиназа-асоцииран липокалин (NGAL) като маркер за бъбречно увреждане при пациенти със захарен диабет (ЗД). Съществен принос са определените възрастово и полово диференцирани референтни граници на pNGAL, uNGAL и uNGAL/uCreatinine (UNC) за българската популация, измерени чрез имунотурбидиметричен анализ, както и разглежданата биологична вариация на маркерите в референтната група. Статистическата обработка на данните показа добра диагностичната надеждност и клиничната приложимост на pNGAL, uNGAL и UNC в диагностиката на диабетно бъбречно заболяване (ДБЗ) при пациенти със ЗД I и ЗД II. Установена е връзката NGAL с маркерите за бъбречно увреждане. Оценена е прогностичната роля на NGAL като маркер за диагноза на ДБЗ при пациенти със ЗД I и ЗД II. Изведени са cut-off стойности, които могат да бъдат приложени в рутинната практика. Оценена е прогностичната роля на NGAL като маркер за прогноза на ДБЗ при пациенти със ЗД I и ЗД II и е определена корелацията на NGAL с маркерите за метаболитен и гликемичен контрол. Констатирана е зависимост в стойностите на uNGAL и UNC от инфекциите на пикочните пътища и левкоцитурията

Clinical significance of human epididymis protein 4 (HE4), cancer antigen 125 (CA125), the risk of ovarian malignancy algorithm (ROMA), and Copenhagen index (CPH-I) for the diagnosis of endometrial carcinoma

Introduction: Endometrial carcinoma (EC) is the most common gynecological cancer among women, and in more than 90% of cases, the initial manifestation of the disease is postmenopausal bleeding. Unfortunately, despite early diagnosis and treatment, EC often recurs. Among the many serum tumor markers studied, human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) show the most promise as tools for EC diagnosis, prognosis, and monitoring. Aim: The aim of the current study was to evaluate the clinical usefulness of HE4 and CA125, tested either as single markers or in combination by including them in the Risk of Ovarian Malignancy Algorithms (ROMA) and in Copenhagen index (CPH-I). Material and methods: In this retrospective study, 1262 women (74 with confirmed EC) were included. The patients with EC had significantly higher values for HE4, CA125, ROMA, and CPH-I (p<0.001) than the healthy women and patients with benign diseases. The subgroup analysis based on the histological type of EC revealed that the highest markers and algorithms were recorded in type II EC group. Results: The ROC curve analysis showed that the best diagnostic performance for detecting EC among patients with benign diseases was the ROMA index (AUC=0.869; 95% CI: 0.818-0.920), followed by CPH-I (AUC=0.822; 95% CI: 0.757-0.887), and HE4 (AUC=0.816; 95% CI: 0.750-0.881). Tested alone, CA125 presented unsatisfactory results for this purpose. Both algorithms proved to have a correlation with the disease stage and progression better than the markers alone (HR=1.046 vs. HR=1.018). Conclusion: In summary, the ROMA index, CPH-I, and, to a lesser extent, standalone HE4 testing can supplement imaging methods as reliable tools for diagnosing and distinguishing patients with EC from those with benign conditions. They have potential as prognostic markers for advanced disease and could help gynecological oncologists to develop a therapeutic strategy

Diagnostic Accuracy of Presepsin, sMR, and Established Inflammatory Biomarkers in Critically Ill Children with Sepsis or Systemic Inflammatory Response Syndrome

Background: Pediatric sepsis is a life-threatening emergency and remains complex to diagnose promptly due to the absence of universally reliable biomarkers. C-reactive protein (CRP) and procalcitonin (PCT) are widely used but have limited effectiveness. We evaluated the diagnostic reliability of presepsin and soluble mannose receptor (sMR) and identified optimal biomarker combinations for distinguishing sepsis from non-infectious systemic inflammatory response syndrome (SIRS) in children. Methods: A total of 80 children were enrolled in this prospective study, including 53 consecutive admissions to the pediatric intensive care unit (PICU) (sepsis, n = 42; non-infectious SIRS, n = 11) and 27 healthy controls. The serum levels of new biomarkers presepsin and soluble mannose receptor (sMR) levels were quantified by ELISA methods and their diagnostic reliability (both individually and combined with CRP and PCT) was assessed using receiver operating characteristic (ROC) curves and multivariate logistic regression. Results: Significantly higher concentrations of all measured markers were found both in septic and other critically ill patients than in healthy controls (p &lt; 0.05). No single biomarker reliably differentiated sepsis from non-infectious SIRS. The sMR + CRP + PCT combination demonstrated the highest diagnostic accuracy (AUC = 0.78, p = 0.0007), surpassing the CRP + PCT model (AUC = 0.71, p = 0.0087). Conclusions: The addition of sMR to the established markers CRP and PCT improves the diagnostic effectiveness in pediatric sepsis. Larger multicenter studies are warranted to confirm clinical utility