Systemic Inflammation in Oncologic Patients Undergoing Systemic Treatment and Receiving Whey Protein-Based Nutritional Support.

There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.

Recommendations for the use of anti-dsDNA autoantibodies in the diagnosis and follow-up of systemic lupus erythematosus - A proposal from an expert panel.

Anti-dsDNA autoantibodies are listed as one of the classification criteria for systemic lupus erythematosus (SLE) and are relatively effective indicators for monitoring disease activity and treatment response. Therefore, clinicians rely on them to diagnose and adjust medication and treatment strategies for SLE patients. However, the use of anti-dsDNA antibodies is not free from controversy. Part of this controversy stems from the fact that anti-dsDNA antibodies are found in several disorders, besides SLE. In addition to this, anti-dsDNA antibodies are a heterogeneous group of antibodies, and their determination still lacks proper standardization. Moreover, anti-dsDNA testing specificity and diagnostic performance change depending on the population under study. These and other issues result in inconsistency and encumber the clinical use of anti-dsDNA antibodies. A panel of medical laboratory and clinical experts on SLE discussed such issues based on their clinical experience in a first meeting, establishing a series of recommendations. The proceedings of this first meeting, plus an exhaustive review of the literature, were used to compose a paper draft. The panel subsequently discussed and refined this draft in a second meeting, the result of which is this paper. This document is relevant to clinical laboratories as it guides to improving diagnosis and monitoring of SLE. Simultaneously, it will help laboratories compile more informative reports, not limited to a mere number. It is also relevant to clinical doctors who wish to better understand laboratory methods so that they can do a more efficient, better-aimed laboratory test ordering.

Longitudinal study of patients with discrepant results in CLIFT and a solid-phase dsDNA antibody assay: does a gold standard dsDNA assay exist?

OBJECTIVE: Antidouble-stranded DNA (dsDNA) antibodies are essential for diagnosis and follow-up of systemic lupus erythematous (SLE). To ensure the best diagnostic approach, most healthcare laboratories opt for a combination of highly sensitive methods, such as solid-phase immunoassays, and highly specific methods, such as the Crithidia luciliae indirect immunofluorescence test (CLIFT). Even so, discordant results are common, thus hindering the diagnostic process. Therefore, this study aimed to characterise a cohort of patients with discrepant results for a dsDNA fluorescence enzyme immunoassay (FEIA) and CLIFT during 2016-2018 and to follow patients up until December 2021. METHODS: We performed an observational, longitudinal and retrospective study on 417 samples from 257 patients who had been referred for suspected connective tissue diseases or followed up after diagnosis. All of them were positive for antinuclear antibodies (ANAs) using an indirect immunofluorescence assay (IFA) on Hep-2 cells, the entry criterion in our laboratory, and positive for FEIA dsDNA. Samples were then tested with CLIFT according to our routine protocol, which includes CLIFT testing after FEIA dsDNA results ≥10 UI/ml. After the assessment of data quality, the final analysis was based on 222 patients. RESULTS: Eighty-three patients (37.4%) had positive results in both tests and met the diagnostic criteria for SLE. However, 139 patients (62.6%) had discrepant results (FEIA+, CLIFT-). Of these, 58 patients (41.7%) had a diagnosis of SLE, with 47 (33.8%) having been previously diagnosed and under treatment. The remaining 11 patients (7.9%) had a new diagnosis of SLE, which was made up within 4 years of the initial screening. A total of 81 of the 139 patients (57.5%) with discrepant results did not meet lupus criteria during the follow-up period. CONCLUSIONS: The study showed that CLIFT could be negative in both treated and newly diagnosed SLE, thus underlining the importance of follow-up of dsDNA-positive results using solid-phase tests. Therefore, quantitative tests such as FEIA could add value to the diagnosis and management of patients with suspected SLE.

Improved gestational diabetes screening protocol.

Objectives: This work aimed to assess the diagnostic validity of two approaches for the screening of gestational diabetes mellitus (GDM) with less discomfort for pregnant women. Methods: A prospective diagnostic validation study was conducted with 2007 pregnant women. According to risk factors for GDM, women were classified into high-risk and low-risk groups. The current diagnostic procedure, based on oral glucose overload, was followed; simultaneously HbA1c was tested and an algorithm combining both biomarkers was applied. Results: In the low-risk group, the Glucose challenge test (GCT) showed a higher area under the curve (AUC 0.953; 95% CI 0.915-0.992) than the HbA1c test (0.688; 95% CI 0.541-0.834). The best GCT cut-off, 153.5 mg/dL (8.52 mmol/L), showed higher diagnostic validity than that for HbA1c, 28 mmol/mol (4.75%), and that the algorithm using both tests. In the high-risk group, the GCT showed better diagnostic performance than the HbA1c and the algorithm; the optimal GCT cut-offs were higher than those recommended in current protocols. 13th week: GCT AUC 0.882 (95% CI 0.843-0.921), HbA1c AUC 0.624 (95% CI 0.562-0.686), GCT cut-off 140.5 mg/dL (7.8 mmol/L), HbA1c cut-off 33 mmol/mol (5.15%). 24th week: GCT AUC 0.944 (95% CI 0.925-0.962), HbA1c AUC 0.642 (95% CI 0.575-0.709), GCT cut-off, 145.5 mg/dL (8.08 mmol/L), HbA1c cut-off 29 mmol/mol (4.85%). Conclusions: The GDM diagnostic approach using as the first step the GCT with higher cut-offs showed the best diagnostic validity. Applying these thresholds, 55.6 and 13.7% of 100 g. Oral glucose overloads would have been avoided in low-risk and high-risk pregnant women.

Association of anti-Ro52, anti-Ro60 and anti-La antibodies with diagnostic, clinical and laboratory features in a referral hospital in Jerez, Spain / Asociación de los anticuerpos anti-Ro52, anti-Ro60 y anti-La con las características diagnósticas, clínicas y de laboratorio en un hospital de referencia en Jerez, España

Objective. Several antibodies have proven to be useful in autoimmune diseases, as markers for diagnosis, prognosis or clinical manifestations. Our objective was to evaluate the diagnosis and manifestations associated for antibodies anti-Ro52, anti-Ro60 and anti-La at a referral hospital in Spain. Methods. We retrospectively analyzed the antigenic specificities of the consecutive samples submitted to the Immunology Unit for antinuclear antibody screening between 2002 and 2012. We included patients with more than one positive sample for some of the autoantibodies anti-Ro52, anti-Ro60 or anti-La. We also reviewed diagnosis, clinical and laboratory features. As dependent variable we evaluated possible combinations of anti-Ro52, anti-Ro60 and anti-La. Results. 322 patients, 91% females, were studied (age 44.3±15.51 years). The most frequent diagnosis was Sjögren's syndrome (40.06%) and systemic lupus erythematosus (SLE) (36.6%). The most prevalent pattern by indirect immunofluorescence was the fine speckled (69.9%). Anti-Ro52+/anti-Ro60+/anti-La+ combination was positively associated with fine speckled pattern (p: 0.001) and negatively with homogeneous (p: 0.016) and cytoplasmic pattern (p: 0.002). Isolated anti-Ro52+ was negatively associated with fine speckled pattern (p<0.001) and positively with the cytoplasmic one (p<0.001). The main positive associations with clinical symptoms were xerostomia and xerophthalmia with anti-Ro52+/anti-Ro60+/anti-La+ (p<0.001), oral ulcers with anti-Ro52+/anti-Ro60+/anti-La− (p: 0.002) and alopecia with anti-Ro52−/anti-Ro60+/anti-La− (p: 0.003). Negative associations were xerophthalmia and photosensitivity with anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). Laboratory positive associations were hypergammaglobulinemia with anti-Ro52+/anti-Ro60+/anti-La+ (p: 0.003), and hypocomplementemia with anti-Ro52−/anti-Ro60+/anti-La− (p: 0.003). Leucopenia was negatively associated with anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). Conclusion. Our study found significant relationships between clinical and laboratory manifestations with different patterns of antibodies to anti-Ro52, anti-Ro60 and anti-La. The combination of antibodies might be clinically useful due to prognostic and therapeutic implications (AU)

Objetivo. Varios anticuerpos han demostrado ser útiles en enfermedades autoinmunes, como marcadores de diagnóstico, pronóstico o manifestaciones clínicas. Nuestro objetivo fue evaluar el diagnóstico y las manifestaciones asociadas a anticuerpos anti-Ro52, anti-Ro60 y anti-La en un hospital de referencia en España. Métodos. Se analizaron retrospectivamente las especificidades antigénicas de todas las muestras consecutivas solicitadas a la Unidad de Inmunología para la detección de anticuerpos antinucleares entre 2002 y 2012. Se incluyeron pacientes con más de una muestra positiva para algunos de los autoanticuerpos anti-Ro52, anti-Ro60 o anti-La, y se revisaron sus características diagnósticas, clínicas y de laboratorio. Como variable dependiente se evaluaron las combinaciones de anti-Ro52, anti-Ro60 y anti-La. Resultados. 322 pacientes, 91% mujeres, fueron estudiados (edad 44.3±15.51 años). El diagnóstico más frecuente fue el síndrome de Sjögren (40.06%), y el lupus eritematoso sistémico (LES) (36.6%). El patrón por inmunofluorescencia indirecta más prevalente fue el moteado fino (69.9%). La combinación Anti-Ro52+/anti-Ro60+/anti-La+ se asoció positivamente con el patrón moteado fino (p: 0.001) y negativamente con el homogéneo (p: 0.016) y el citoplasmático (p: 0.002). Anti-Ro52+ aislado se asoció negativamente con el patrón moteado fino (p<0.001) y positivamente con el citoplasmático (p<0.001). La principal asociación con síntomas clínicos fue de xerostomía y xeroftalmia con anti-Ro52+/anti-Ro60+/anti-La+ (p<0.001), úlceras orales con anti-Ro52+/anti-Ro60+/anti-La− (p: 0.002) y alopecia con anti-Ro52−/anti-Ro60+/anti-La−. Asociaciones negativas fueron xeroftalmia y fotosensibilidad con anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). Asociaciones positivas de laboratorio fueron hipergammaglobulinemia con anti-Ro52+/anti-Ro60+/anti-La+ (p: 0.003) e hipocomplementemia con anti-Ro52−/anti-Ro60+/anti-La− (p: 0.003). Leucopenia se asoció negativamente con anti-Ro52+/anti-Ro60−/anti-La− (p: 0.003). Conclusión. Nuestro estudio encontró una relación significativa entre las manifestaciones clínicas y de laboratorio con diferentes patrones de anticuerpos anti-Ro52, anti-Ro60 y anti-La. La combinación de anticuerpos podría ser clínicamente útil, debido a implicaciones pronósticas y terapéuticas (AU)

Association of anti-Ro52, anti-Ro60 and anti-La antibodies with diagnostic, clinical and laboratory features in a referral hospital in Jerez, Spain.

OBJECTIVE: Several antibodies have proven to be useful in autoimmune diseases, as markers for diagnosis, prognosis or clinical manifestations. Our objective was to evaluate the diagnosis and manifestations associated for antibodies anti-Ro52, anti-Ro60 and anti-La at a referral hospital in Spain. METHODS: We retrospectively analyzed the antigenic specificities of the consecutive samples submitted to the Immunology Unit for antinuclear antibody screening between 2002 and 2012. We included patients with more than one positive sample for some of the autoantibodies anti-Ro52, anti-Ro60 or anti-La. We also reviewed diagnosis, clinical and laboratory features. As dependent variable we evaluated possible combinations of anti-Ro52, anti-Ro60 and anti-La. RESULTS: 322 patients, 91% females, were studied (age 44.3±15.51 years). The most frequent diagnosis was Sjögren's syndrome (40.06%) and systemic lupus erythematosus (SLE) (36.6%). The most prevalent pattern by indirect immunofluorescence was the fine speckled (69.9%). Anti-Ro52+/anti-Ro60+/anti-La+ combination was positively associated with fine speckled pattern (p: 0.001) and negatively with homogeneous (p: 0.016) and cytoplasmic pattern (p: 0.002). Isolated anti-Ro52+ was negatively associated with fine speckled pattern (p<0.001) and positively with the cytoplasmic one (p<0.001). The main positive associations with clinical symptoms were xerostomia and xerophthalmia with anti-Ro52+/anti-Ro60+/anti-La+ (p<0.001), oral ulcers with anti-Ro52+/anti-Ro60+/anti-La- (p: 0.002) and alopecia with anti-Ro52-/anti-Ro60+/anti-La- (p: 0.003). Negative associations were xerophthalmia and photosensitivity with anti-Ro52+/anti-Ro60-/anti-La- (p: 0.003). Laboratory positive associations were hypergammaglobulinemia with anti-Ro52+/anti-Ro60+/anti-La+ (p: 0.003), and hypocomplementemia with anti-Ro52-/anti-Ro60+/anti-La- (p: 0.003). Leucopenia was negatively associated with anti-Ro52+/anti-Ro60-/anti-La- (p: 0.003). CONCLUSION: Our study found significant relationships between clinical and laboratory manifestations with different patterns of antibodies to anti-Ro52, anti-Ro60 and anti-La. The combination of antibodies might be clinically useful due to prognostic and therapeutic implications.