Predictive potential of serum and cerebrospinal fluid biomarkers for disease activity in treated multiple sclerosis patients.

BACKGROUND: Our objective was to explore various biomarkers for predicting suboptimal responses to disease-modifying treatments (DMTs) in patients with MS (pwMS). METHODS: We conducted a longitudinal, bicentric study with pwMS stratified based on their DMTs responses. Treatment failure (TF) was defined as the onset of a second relapse, presence of two or more T2 new lesions, or disability progression independent of relapse during the follow-up period. We evaluated intrathecal synthesis (ITS) of IgG and IgM using OCB, linear indices, and Reibergrams. Free kappa light chains ITS was assessed using the linear index (FKLCi). NfL and GFAP in serum and CSF, and CHI3L1 in CSF were quantified. Quantitative variables were dichotomized based on the third quartile. Predictive efficacy was assessed through bivariate and multivariate analyses, adjusting for age, sex, EDSS, acute inflammatory activity (AI) -defined as the onset of a relapse or gadolinium-enhancing lesions within a 90-day window of lumbar puncture-, treatment modality, study center, and time from disease onset to treatment initiation. In case of collinearity, multiple models were generated or confounding variables were excluded if collinearity existed between them and the biomarker. The same methodology was used to investigate the predictive potential of various combinations of two biomarkers, based on whether any of them tested positive or exceeded the third quartile. RESULTS: A total of 137 pwMS were included. FKLCi showed no differences based on AI, no correlation with EDSS and was significantly higher in pwMS with TF (p = 0.008). FKLCi>130 was associated with TF in bivariate analysis (Log-Rank p = 0.004). Due to collinearity between age and EDSS, two different models were generated with each of them and the rest of the confounding variables, in which FKLCi>130 showed a Hazard Ratio (HR) of 2.69 (CI: 1.35-5.4) and 2.67 (CI: 1.32-5.4), respectively. The combination of either FKLC or sNfL exceeding the third quartile was also significant in bivariate (Log-Rank p = 0.04) and multivariate (HR=3.1 (CI: 1.5-6.5)) analyses. However, when analyzed independently, sNfL did not show significance, and FKLCi mirrored the pattern obtained in the previous model (HR: 3.04; CI: 1.51-6.1). Treatment with highefficacy DMTs emerged as a protective factor in all models. DISCUSSION: Our analysis and the fact that FKLCi is independent of EDSS and AI suggest that it might be a valuable parameter for discriminating aggressive phenotypes. We propose implementing high-efficacy drugs in pwMS with elevated FKLCi.

Endothelial Damage, Neutrophil Extracellular Traps and Platelet Activation in COVID-19 vs. Community-Acquired Pneumonia: A Case-Control Study.

COVID-19 has been a diagnostic and therapeutic challenge. It has marked a paradigm shift when considering other types of pneumonia etiology. We analyzed the biomarkers related to endothelial damage and immunothrombosis in COVID-19 in comparison to community-acquired pneumonia (CAP) through a case-control study of 358 patients with pneumonia (179 hospitalized with COVID-19 vs. 179 matched hospitalized with CAP). Endothelial damage markers (endothelin and proadrenomedullin), neutrophil extracellular traps (NETs) (citrullinated-3 histone, cell-free DNA), and platelet activation (soluble P-selectin) were measured. In-hospital and 1-year follow-up outcomes were evaluated. Endothelial damage, platelet activation, and NET biomarkers are significantly higher in CAP compared to COVID-19. In-hospital mortality in COVID-19 was higher compared to CAP whereas 1-year mortality and cardiovascular complications were higher in CAP. In the univariate analysis (OR 95% CIs), proADM and endothelin were associated with in-hospital mortality (proADM: CAP 3.210 [1.698-6.070], COVID-19 8.977 [3.413-23.609]; endothelin: CAP 1.014 [1.006-1.022], COVID-19 1.024 [1.014-1.034]), in-hospital CVE (proADM: CAP 1.623 [1.080-2.439], COVID-19 2.146 [1.186-3.882]; endothelin: CAP 1.005 [1.000-1.010], COVID-19 1.010 [1.003-1.018]), and 1-year mortality (proADM: CAP 2.590 [1.644-4.080], COVID-19 13.562 [4.872-37.751]; endothelin: CAP 1.008 [1.003-1.013], COVID-19 1.026 [1.016-1.037]). In conclusion, COVID-19 and CAP showed different expressions of endothelial damage and NETs. ProADM and endothelin are associated with short- and long-term mortality.

Peripheral T-cell lymphoma with a T follicular-helper phenotype: A different entity? Results of the Spanish Real-T study.

Nodal peripheral T-cell lymphoma (PTCL) with a T follicular helper phenotype (PTCL-TFH) is a new type of PTCL. We aimed to define its clinical characteristics and prognosis compared to PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). This retrospective observational study included 175 patients diagnosed with PTCL between 2008 and 2013 in 13 Spanish sites. Patient diagnosis was centrally reviewed, and patients were reclassified according to the World Health Organization (WHO) 2016 criteria: 21 patients as PTCL-NOS, 55 as AITL and 23 as PTCL-TFH. Median follow-up was 56.07 months (95% CI 38.7-73.4). Progression-free survival (PFS) and overall survival (OS) were significantly higher in patients with PTCL-TFH than in those with PTCL-NOS and AITL (PFS, 24.6 months vs. 4.6 and 7.8 months, respectively, p = 0.002; OS, 52.6 months vs. 10.0 and 19.3 months, respectively, p < 0.001). Histological diagnosis maintained an independent influence on both PFS (hazard ratio [HR] 4.1 vs. PTCL-NOS, p = 0.008; HR 2.6 vs. AITL, p = 0.047) and OS (HR 5.7 vs. PTCL-NOS, p = 0.004; HR 2.6 vs. AITL, p = 0.096), regardless of the International Prognostic Index. These results suggest that PTCL-TFH could have more favourable features and prognosis than the other PTCL subtypes, although larger series are needed to corroborate these findings.

Neutrophil Extracellular Traps and Platelet Activation for Identifying Severe Episodes and Clinical Trajectories in COVID-19.

The role of NETs and platelet activation in COVID-19 is scarcely known. We aimed to evaluate the role of NETs (citrullinated histone H3 [CitH3], cell-free DNA [cfDNA]) and platelet activation markers (soluble CD40 ligand [CD40L] and P-selectin) in estimating the hazard of different clinical trajectories in patients with COVID-19. We performed a prospective study of 204 patients, categorized as outpatient, hospitalized and ICU-admitted. A multistate model was designed to estimate probabilities of clinical transitions across varying states, such as emergency department (ED) visit, discharge (outpatient), ward admission, ICU admission and death. Levels of cfDNA, CitH3 and P-selectin were associated with the severity of presentation and analytical parameters. The model showed an increased risk of higher levels of CitH3 and P-selectin for ED-to-ICU transitions (Hazard Ratio [HR]: 1.35 and 1.31, respectively), as well as an elevated risk of higher levels of P-selectin for ward-to-death transitions (HR: 1.09). Elevated levels of CitH3 (HR: 0.90), cfDNA (HR: 0.84) and P-selectin (HR: 0.91) decreased the probability of ward-to-discharge transitions. A similar trend existed for elevated levels of P-selectin and ICU-to-ward transitions (HR 0.40); In conclusion, increased NET and P-selectin levels are associated with more severe episodes and can prove useful in estimating different clinical trajectories.

Acute and sustained increase in endothelial biomarkers in COVID-19.

Endothelial injury is related to poor outcomes in respiratory infections yet little is known in relation to COVID-19. Performing a longitudinal analysis (on emergency department admission and post-hospitalisation follow-up), we evaluated endothelial damage via surrogate systemic endothelial biomarkers, that is, proadrenomedullin (proADM) and proendothelin, in patients with COVID-19. Higher proADM and/or proendothelin levels at baseline were associated with the most severe episodes and intensive care unit admission when compared with ward-admitted individuals and outpatients. Elevated levels of proADM or proendothelin at day 1 were associated with in-hospital mortality. High levels maintained after discharge were associated with reduced diffusing capacity.

Perforación intestinal secundaria a linfoma intestinal B difuso de células grandes en un paciente con enfermedad celiaca / Intestinal perforation secondary to intestinal diffuse large b-cell lymphoma in a patient with coeliac disease

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Síndrome de cauda equina secundario a neurolinfomatosis: presentación de un caso y revisión de la literatura / Cauda equina syndrome secondary to neurolymphomatosis: Case report and literature review

La neurolinfomatosis es una entidad rara caracterizada por la presencia de linfocitos neoplásicos que infiltran las estructuras del sistema nervioso periférico. Dada su naturaleza y localización puede desarrollar una gran variedad de síntomas, suponiendo un reto diagnóstico. El tratamiento se basa en el uso de metotrexato, aunque, a día de hoy, existen diversos esquemas de quimioterapia para los pacientes con enfermedad sistémica. Presentamos el caso de un varón con neurolinfomatosis a nivel de la cauda equina y agrupamos los casos descritos hasta el momento

Neurolymphomatosis is a rare disorder characterised by infiltration of neoplastic lymphocytes into the peripheral nervous system. A wide variety of symptoms can manifest depending on its nature and location, making its diagnosis a real challenge. Treatment is based on methotrexate, although various chemotherapy regimens are currently available for patients with systemic disease. We present the case of a male patient with neurolymphomatosis of the cauda equina, together with a review of all cases published to date

Cauda equina syndrome secondary to neurolymphomatosis: Case report and literature review. / Síndrome de cauda equina secundario a neurolinfomatosis: presentación de un caso y revisión de la literatura.

Neurolymphomatosis is a rare disorder characterised by infiltration of neoplastic lymphocytes into the peripheral nervous system. A wide variety of symptoms can manifest depending on its nature and location, making its diagnosis a real challenge. Treatment is based on methotrexate, although various chemotherapy regimens are currently available for patients with systemic disease. We present the case of a male patient with neurolymphomatosis of the cauda equina, together with a review of all cases published to date.

Sarcoma histiocítico con rasgos inmunohistoquímicos yultraestructurales de células dendríticas interdigitantes / Histiocytic sarcoma with immunohistochemical and ultraestructural interdigitating dendritic cell features

Introducción: El Sarcoma histiocítico (SH) es una neoplasiamuy poco frecuente, con mucha controversia respectoa los criterios diagnósticos de esta entidad. Desde que lastécnicas inmunohistoquímicas y citogenéticas presentan unamayor disponibilidad universal, muchos casos que inicialmentese diagnosticaron como sarcoma histiocítico, hansido reclasificados como otras enfermedades. Presentacióndel caso: Describimos el caso de un sarcoma histiocíticoque se presentó como una masa abdominal. En la autopsiatambién se observó afectación tumoral de pulmones, hígado,bazo y múltiples adenopatías. El examen histológicomostró proliferación difusa de células grandes con áreas denecrosis. Las células malignas eran de aspecto histiocitarioy pleomórficas. Inmunohistoquímicamente, las célulastumorales fueron positivas para tinciones contra marcadoreshistiocíticos y negativas para marcadores mieloides, dendríticos,CD30, ALK1, y otros marcadores linfoides. En elestudio ultraestructural las células mostraron extensionescitoplásmicas interdigitantes, pero no gránulos de Birbeck.Conclusiones: El sarcoma histiocítico plantea diagnósticodiferencial con otras neoplasias. El diagnóstico en este caso,se basa en la morfología, técnicas inmunohistoquícas yultraestructurales (AU)

Introduction: Histiocytic sarcoma (HS) is a rare disease.There has been much confusion concerning the diagnosticcriteria for this entity. Since immunohistochemicaland cytogenetic techniques have become more universallyavailable, many cases that were initially diagnosed as histiocyticsarcoma are now being classified as other diseases.Case presentation:We describe a case of HS that began asabdominal mass. At autopsy the tumour also involved lungs,liver, spleen and multiple lymph nodes. Histological examinationshowed proliferation of numerous large histiocyticpleomorphic and malignant cells with areas of necrosis.Immunohistochemically, tumour cells expressed histiocyticmarkers but did not stain with antibodies directed againstmyeloid markers, dendritic markers, CD30, ALK1, or otherlymphoid markers. Ultrastructural examination demostratedinterdigitating cytoplasmic extensions, but not Birbeckgranules. Conclusions: Histiocytic sarcoma raises differentialdiagnosis with other neoplasms. In this case, morphological,immunohistochemical and ultraestructural findingsare necessary for diagnosis (AU)

[Extrarenal retroperitoneal angiomyolipoma: bibliography review and report of a new case]. / Angiomiolipoma pararrenal: "revisión de la bibliografía" y presentación de un nuevo caso.

OBJECTIVES: To report the 7th case of pararenal angiomyolipoma published in the world literature and to review the international bibliography. METHODS: We report the case of a 46-year-old female with history of renal colic and a complex mass on radiological tests. RESULTS/CONCLUSIONS: Extrarenal retroperitoneal angiomyolipoma is a rare pathology with no more than 7 published cases. The diagnostic difficulty and radiological similarities with liposarcoma make surgery the treatment of choice.