A sex-dependent algorithm including kappa free light chain for multiple sclerosis diagnosis.

Multiple sclerosis (MS) diagnosis includes the presence of restricted oligoclonal bands (OCB) in cerebrospinal fluid (CSF), but it has several limitations, as it is an observer-dependent time-consuming technique and offers a dichotomous result. Thus kappa free light chains (KFLC) have emerged as a quantitative alternative. However, the cut-off values for KFLC have not been well established yet and it is not clear if differences between sexes exist. We aim to evaluate these and to compare the diagnostic accuracy of KFLC concentrations and their related indexes versus OCB. For that purpose, paired CSF and serum samples were collected and immediately processed for albumin, total protein, immunoglobulins and OCB, then frozen at -20°C. KFLC was measured in a BN II (Siemens Healthineers, Germany). KFLC-derived indexes were calculated. Diagnostic accuracy was evaluated by the area under the curve (AUC), Youden's index and odds ratio. From the 193 patients included, 56 were classified as MS according to the 2017 McDonald criteria. K-index, Q KFLC and Reiber's diagram showed good accuracy in MS diagnosis when studied distinguishing between sexes, similar to OCB. Cut-offs for K-index and Q KFLC change substantially between sex having the highest AUC similar than OCB. A sex-dependent algorithm combining the use of K-index, Q KFLC and OCB yields the highest diagnostic accuracy. In conclusion, CSF KFLC measurement is a rapid, quantitative and easy-to-standardize tool that used through the proposed sex-dependent algorithm may reduce the number of manual OCB tests performed.

Usefulness of several biomarkers in the management of septic patients: C-reactive protein, procalcitonin, presepsin and mid-regional pro-adrenomedullin.

BACKGROUND: Our objective is to analyze whether the combination of C-reactive protein (CRP), procalcitonin (PCT), presepsin or SCD14-ST and mid-regional pro-adrenomedullin (MR-proADM) measured in the first 24 h from ICU admission allowing a better management of septic patients (diagnostic and prognostic) both in severe sepsis (SS) and septic shock (SSh). METHODS: Cohort study of 388 patients admitted in the ICU during 12 months of whom 142 were controls. Biomarkers were measured through immunoluminometric assays in samples of serum or plasma within the first 24 h after admission. Data were evaluated with non-parametric statistics bivariant, ROC curve analysis for diagnostic evaluation and multivariate analyses for survival analysis. RESULTS: In the analyzed cohort, 61.8% of patients were males, mean age: 63 years range (18-90) and 67.8% in controls mean age: 63 years, range (39-91). PCT showed the highest area under the curve (AUC) (0.989) as compared with the rest of biomarkers (p<0.01). PCT also enabled the difference between Gram-positive or Gram-negative bacteria to be determined. The AUCs for CRP (0.922) and presepsin (0.948) showed a similar diagnostic value. In cases of SSh, the AUC of presepsin experienced a noticeable increase (p<0.0001). MR-proADM showed a better prognostic value (p=0.00022) particularly in cases of SSh (p=0.00001) increasing along with the APACHE-II score. CONCLUSIONS: PCT, MR-proADM and presepsin are complementary markers that could be of great help in the management of septic patients when they are measured in the first 24 h after ICU admission.

Homocysteine: new tumor marker in pleural fluid.

There are no published studies examining the utility of total homocysteine (HCY) in pleural fluid. The aim was to measure the accuracy of pleural fluid HCY concentration for diagnosis of malignant pleural effusion (MPE). We studied pleural fluids obtained by thoracocentesis in patients with pleural effusion. Pleural fluid HCY concentration was measured by immunonephelometry using N Latex HCY reagent with monoclonal antibody in automated analyzers BNII (Siemens Diagnostics®). Patients were classified into two groups according to the etiology of pleural effusion: benign pleural effusions (BPE) and MPE. Pleural effusion was categorized as MPE if malignant cells were demonstrated in pleural fluid or pleural biopsy. The accuracy of pleural fluid HCY concentration for diagnosis of MPE was determined using receiver operating characteristic (ROC) techniques by analyzing the area under the ROC curve (AUC). We studied 89 patients with ages between 1 and 96 years old (median = 66). Forty-eight patients were BPE and 41 were MPE. Pleural fluid HCY concentration was significantly higher in patients with MPE (median = 13.70 µmol/L) than in those with BPE (median = 8.05 µmol/L). The AUC value was 0.833 (95 % confidence interval (CI) 0.739-0.903). The optimal cutoff value was 13.1 µmol/L exhibiting 56.1 % (95 % CI 39.8-71.5) sensitivity and 85.4 % (95 % CI 72.2-93.9) specificity. Pleural fluid HCY concentration showed high diagnostic accuracy to predict whether a pleural effusion is benign or malignant. Pleural fluid HCY concentration may be measured easily and quickly in automated analyzers and could be a tumor marker commonly used for diagnosis of MPE.

Serum lactate dehydrogenase in combination with free-to-total serum prostate specific antigen ratio for diagnosis of prostate cancer.

BACKGROUND: Evaluate the utility of serum lactate dehydrogenase (LDH) in combination with free-to-total serum prostate specific antigen ratio (%fPSA), for diagnosis of prostate cancer (PC) with serum total prostate specific antigen (PSA) levels in the intermediate range of 4 to 10 ng/mL. METHODS: The following variables were analysed: PSA, %fPSA, and LDH. Two categories of patients were included in the analysis: NOT PC and PC. RESULTS: We studied 134 patients, 112 had NOT PC and 22 had PC. We defined the following multivariable score (S): S = A + B, where A and B are coefficients of LDH and %fPSA, respectively. AUC values were 0.719 (p = 0.0036), 0.749 (p = 0.0082), and 0.816 (p = 0.0001) for %fPSA, LDH, and S, respectively. Using the proposed S increases by 18% specificity compared to only using the %fPSA parameter. CONCLUSIONS: LDH in combination with %fPSA improves diagnostic performance for detection of PC compared to using only %fPSA.

Biochemical biomarkers for multiple sclerosis.

INTRODUCTION: Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous system. Although there is currently no definite cure for MS, new therapies have recently been developed based on a continuous search for new biomarkers. DEVELOPMENT: MS diagnosis relies on the integration of clinical, imaging and laboratory findings as there is still no singlepathognomonicclinical feature or diagnostic laboratory biomarker. The most commonly laboratory test used is the presence of immunoglobulin G oligoclonal bands (OCB) in cerebrospinal fluid of MS patients. This test is now included in the 2017 McDonald criteria as a biomarker of dissemination in time. Nevertheless, there are other biomarkers currently in use such as kappa free light chain, which has shown higher sensitivity and specificity for MS diagnosis than OCB. In addition, other potential laboratory tests involved in neuronal damage, demyelination and/or inflammation could be used for detecting MS. CONCLUSIONS: CSF and serum biomarkers have been reviewed for their use in MS diagnosis and prognosis to stablish an accurate and prompt MS diagnosis, crucial to implement an adequate treatment and to optimize clinical outcomes over time.

Lamellar structures of MUC2-rich mucin: a potential role in governing the barrier and lubricating functions of intestinal mucus.

Mucus is a ubiquitous feature of mammalian wet epithelial surfaces, where it lubricates and forms a selective barrier that excludes a range of particulates, including pathogens, while hosting a diverse commensal microflora. The major polymeric component of mucus is mucin, a large glycoprotein formed by several MUC gene products, with MUC2 expression dominating intestinal mucus. A satisfactory answer to the question of how these molecules build a dynamic structure capable of playing such a complex role has yet to be found, as recent reports of distinct layers of chemically identical mucin in the colon and anomalously rapid transport of nanoparticles through mucus have emphasized. Here we use atomic force microscopy (AFM) to image a MUC2-rich mucus fraction isolated from pig jejunum. In the freshly isolated mucin fraction, we find direct evidence for trigonally linked structures, and their assembly into lamellar networks with a distribution of pore sizes from 20 to 200 nm. The networks are two-dimensional, with little interaction between lamellae. The existence of persistent cross-links between individual mucin polypeptides is consistent with a non-self-interacting lamellar model for intestinal mucus structure, rather than a physically entangled polymer network. We only observe collapsed entangled structures in purified mucin that has been stored in nonphysiological conditions.

The diagnostic value of pleural fluid homocysteine in malignant pleural effusion.

BACKGROUND: Pleural fluid homocysteine (HCY) can be useful for diagnosis of malignant pleural effusion (MPE). There are no published studies comparing the diagnostic accuracy of HCY with other tumour markers in pleural fluid for diagnosis of MPE. The aim was to compare the accuracy of HCY with that of carcinoembryonic antigen (CEA), cancer antigen (CA) 15.3, CA19.9 and CA125 in pleural fluid and to develop a probabilistic model using these biomarkers to differentiate benign (BPE) from MPE. METHODS: Patients with pleural effusion were randomly included. HCY, CEA, CA15.3, CEA19.9 and CA125 were quantified in pleural fluid. Patients were classified into two groups: MPE or BPE. By applying logistic regression analysis, a multivariate probabilistic model was developed using pleural fluid biomarkers. The diagnostic accuracy was determined by receiver operating characteristic (ROC) curves and calculating the area under the curve (AUC). RESULTS: Population of study comprised 133 patients (72 males and 61 females) aged between 1 and 96 years (median = 70 years), 81 BPE and 52 MPE. The logistic regression analysis included HCY (p<0.0001) and CEA (p = 0.0022) in the probabilistic model and excluded the other tumour markers. The probabilistic model was: HCY+CEA = Probability(%) = 100×(1+e-z)-1, where Z = 0.5471×[HCY]+0.3846×[CEA]-8.2671. The AUCs were 0.606, 0.703, 0.778, 0.800, 0.846 and 0.948 for CA125, CA19.9, CEA, CA15.3, HCY and HCY+CEA, respectively. CONCLUSIONS: Pleural fluid HCY has higher accuracy for diagnosis of MPE than CEA, CA15.3, CA19.9 and CA125. The combination of HCY and CEA concentrations in pleural fluid significantly improves the diagnostic accuracy of the test.

Mid-regional pro-adrenomedullin as prognostic biomarker in septic shock.

BACKGROUND: The aim was to ascertain the prognostic value of mid-regional pro-adrenomedullin (MR-proADM), measured within 24 hours from the onset of septic shock (SS). METHODS: We performed a prospective, observational study on all patients admitted to our hospital's Intensive Care Unit with SS over a one year period from January to December 2011 to examine the outcomes in 100 consecutive SS cases. Demographic data and severity score (APACHEII and SOFA) were recorded. MR-proADM, C-reactive protein and procalcitonin were measured within the first 24 hours from SS onset. The outcome variable studied was 28-day mortality. Data were evaluated with non-parametric statistics bivariant and multivariate analyses for survival analysis. RESULTS: In patients who died within 28 days (36%), MR-proADM, Lactate, APACHE II as well as SOFA were significantly higher compared with survivors. MR-proADM showed the best association with 28-day mortality, as well as a prognostic value (logrank test: P=0.0012). Statistical significance was also seen in the Cox regression analysis (P=0.0004) for all patients with a Relative Risk of 1.26 times that of the baseline for each mmol/L of increase in MR-proADM. CONCLUSIONS: In our study MR-proADM levels measured on admission correlates with 28-day mortality in patients with septic shock.

Síndrome de Sweet mielodisplásico corticodependiente. A propósito de un caso / Corticosteroid-dependent myelodysplastic Sweet's syndrome. Presentation of a case

Fundamento y objetivo: El síndrome de Sweet o dermatosis neutrofílica febril aguda es una enfermedad inflamatoria infrecuente de fisiopatología desconocida, aunque las evidencias clínicas y bioquímicas sugieren que las citocinas tienen un papel importante en su etiopatogenia. Se distinguen 5 grupos etiológicos: idiopático, parainflamatorio, secundario a fármacos, asociado a embarazo y paraneoplásico. Este último grupo representa el 20% de los casos, asociados el 85% de ellos a neoplasias hematológicas y el 15% a tumores sólidos. Paciente: Se presenta el caso de un paciente afecto de síndrome de Sweet con afectación dermatológica atípica, asociado a un síndrome mielodisplásico y también a un síndrome de Cushing iatrogénico secundario a altas dosis de corticoides cuya evolución fue desfavorable. Resultados: Positividad de los reactantes de fase aguda (RFA) durante los brotes, destacando la elevación precoz de la interleucina 6 (IL-6) seguida del seroamiloide A (SAA) y proteína C reactiva (PCR), encontrándose diferencias estadísticamente significativas (p<0,05) entre la PCR y el SAA. Conclusiones: Un síndrome de Sweet en un varón con múltiples recaídas y localización dermatológica no clásica, cuando se asocia a alteraciones hematológicas, con un incremento de los RFA y elevación precoz de la IL-6 debe orientar el diagnóstico clínico hacia un origen paraneoplásico y hematológico

Background and objective: Sweet's syndrome or acute febrile neutrophilic dermatosis is a rare inflammatory disease of unknown pathophysiology, although clinical and biochemical evidence suggests that cytokines play an important role in its aetiopathogenesis. It is classified into five groups: idiopathic, para-inflammatory, secondary to drugs, associated with pregnancy, and para-neoplastic in 20% of cases, with 85% of these linked to haematological disorders, and 15% to solid tumours. Patient: A report is presented on a patient with Sweet's Syndrome with atypical dermatological involvement, associated with myelodysplastic syndrome, and iatrogenic Cushing's syndrome secondary to high-doses of corticosteroids, with an unfavorable outcome. Results: Acute phase reactants (APR) were increased during the outbreaks, with the early elevation of interleukin 6 (IL6) being highlighted, followed by serum amyloid A (SAA) and C-reactive protein (CRP), with statistically significant differences (P<.05) between CRP and SAA. Conclusions: A Sweet's syndrome in a male with multiple relapses and a non-classical dermatological location, associated haematological abnormalities, and an increase in APR with early elevation of IL6, should lead to a clinical diagnosis of paraneoplastic and haematological origin

Nueva mutación en una familia española con síndrome de hiperferritinemia hereditaria y cataratas / New mutation in a Spanish family with hereditary hyperferritinemia-cataract syndrome

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