Development of a novel multiplex beads-based assay for autoantibody detection for colorectal cancer diagnosis.

Humoral response in cancer patients can be used for early cancer detection. By screening high-density protein microarrays with sera from colorectal cancer (CRC) patients and controls, we identified 16 tumor-associated antigens (TAAs) exhibiting high diagnostic value. This high number of TAAs requires the development of multiplex assays combining different antigens for a faster and more accurate prediction of CRC. Here, we have developed and optimized a bead-based assay using nine selected TAAs and two controls to provide a multiplex test for early CRC diagnosis. We screened a collection of 307 CRC patients' and control sera with the beads assay to identify and validate the best TAA combination for CRC detection. The multiplex bead-based assay exhibited a similar diagnostic performance to detect the humoral response in comparison to multiple ELISA analyses. After multivariate analysis, a panel composed of GTF2B, EDIL3, HCK, PIM1, STK4, and p53, together with gender and age, was identified as the best combination of TAAs for CRC diagnosis, achieving an AUC of 89.7%, with 66% sensitivity at 90.0% fixed specificity. The model was validated using bootstrapping analysis. In summary, we have developed a novel multiplex bead assay that after validation with a larger independent cohort of sera could be utilized in a high-throughput manner for population screening to facilitate the detection of early CRC patients.

In-depth characterization of the secretome of colorectal cancer metastatic cells identifies key proteins in cell adhesion, migration, and invasion.

Liver metastasis in colorectal cancer is the major cause of cancer-related deaths. To identify and characterize proteins associated with colon cancer metastasis, we have compared the conditioned serum-free medium of highly metastatic KM12SM colorectal cancer cells with the parental, poorly metastatic KM12C cells using quantitative stable isotope labeling by amino acids in cell culture (SILAC) analyses on a linear ion trap-Orbitrap Velos mass spectrometer. In total, 1337 proteins were simultaneously identified in SILAC forward and reverse experiments. For quantification, 1098 proteins were selected in both experiments, with 155 proteins showing >1.5-fold change. About 52% of these proteins were secreted directly or using alternative secretion pathways. GDF15, S100A8/A9, and SERPINI1 showed capacity to discriminate cancer serum samples from healthy controls using ELISAs. In silico analyses of deregulated proteins in the secretome of metastatic cells showed a major abundance of proteins involved in cell adhesion, migration, and invasion. To characterize the tumorigenic and metastatic properties of some top up- and down-regulated proteins, we used siRNA silencing and antibody blocking. Knockdown expression of NEO1, SERPINI1, and PODXL showed a significant effect on cellular adhesion. Silencing or blocking experiments with SOSTDC1, CTSS, EFNA3, CD137L/TNFSF9, ZG16B, and Midkine caused a significant decrease in migration and invasion of highly metastatic cells. In addition, silencing of SOSTDC1, EFNA3, and CD137L/TNFSF9 reduced liver colonization capacity of KM12SM cells. Finally, the panel of six proteins involved in invasion showed association with poor prognosis and overall survival after dataset analysis of gene alterations. In summary, we have defined a collection of proteins that are relevant for understanding the mechanisms underlying adhesion, migration, invasion, and metastasis in colorectal cancer.

Long-Term Benefit of Perlingual Polybacterial Vaccines in Patients with Systemic Autoimmune Diseases and Active Immunosuppression.

INTRODUCTION: We have previously shown that trained-immunity-based vaccines, namely TIbV, significantly reduce the rate of recurrent infections, both of the respiratory tract (RRTI) and urinary tract infections (RUTI) in SAD patients on disease-modifying drugs (DMARDs). OBJECTIVE: We evaluated the frequency of RRTI and RUTI from 2018 to 2021 in those SAD patients that received TIbV until 2018. Secondarily, we evaluated the incidence and clinical course of COVID-19 in this cohort. METHODS: A retrospective observational study was conducted in a cohort of SAD patients under active immunosuppression immunized with TIbV (MV130 for RRTI and MV140 for RUTI, respectively). RESULTS: Forty-one SAD patients on active immunosuppression that were given TIbV up to 2018 were studied for RRTI and RUTI during the 2018-2021 period. Approximately half of the patients had no infections during 2018-2021 (51.2% no RUTI and 43.5% no RRTI at all). When we compared the 3-year period with the 1-year pre-TIbV, RRTI (1.61 ± 2.26 vs. 2.76 ± 2.57; p = 0.002) and RUTI (1.56 ± 2.12 vs. 2.69 ± 3.07; p = 0.010) episodes were still significantly lower. Six SAD patients (four RA; one SLE; one MCTD) with RNA-based vaccines were infected with SARS-CoV-2, with mild disease. CONCLUSIONS: Even though the beneficial protective effects against infections of TIbV progressively decreased, they remained low for up to 3 years, with significantly reduced infections compared to the year prior to vaccination, further supporting a long-term benefit of TIbV in this setting. Moreover, an absence of infections was observed in almost half of patients.

Bilateral carcinoma in situ of Wharton's duct after chronic obstructive sialadenitis: inflammation as the cause of malignancy?

A case of bilateral carcinoma in situ of Wharton's duct after chronic sialadenitis is reported. The patient, a 54-year-old man, complained of recurrent pain and swelling in the left lower submandibular region. Computed tomography showed large stones in the hilar area of both submandibular glands. The patient underwent bilateral submandibular excision. Histologic and immunohistochemical examination revealed squamous metaplasia with areas of carcinoma in situ in both right and left ducts adjacent to the calculus. To the best of our knowledge, this is the first case report in the literature describing an association between obstructive sialadenitis and carcinoma in situ of Wharton's duct. We discuss etiologic factors and chronic inflammation as a possible cause of malignancy.

B-cell haematological malignancies and SARS-CoV-2 infection: Could immunological interventions influence the outcome?

B cell haematological malignancies (HMs) have been described as the worst cancer type for concomitant COVID-19 in terms of mortality, with rates up to 65%. This risk factor for COVID-19 cannot only be explained by comorbidities and advanced age of patients, but aggravated by secondary immunodeficiency (SID). We aimed at evaluating the impact of COVID-19 on 86 HM patients with concomitant SID from a single centre. Only 14 HM patients of 86 (16.28%) patients suffered COVID-19, with mortality rate of 7%. When we considered patients according to B-cell defect only or multiple immune defect overlap (B-T-cell/NK cells/complement), patients with immune defect overlap presented 5.30-fold higher risk of COVID-19 than only B cell defect (95% CI, 1.67-17.0) (p = 0.004). Seven (50%) patients were on active IgRT; while five (36%) had received prior mucosal vaccines for respiratory infections. Our results show that modelling SID in HM may contribute to better prediction of infectious risk and to prompt more targeted and timely preventive therapies.

Streptococcus phocae, an emerging pathogen for salmonid culture.

This work describes the characterization of the causal agent of disease outbreaks that, from 1999, occurred repeatedly during the summer months (temperatures higher than 15 degrees C) in Atlantic salmon (Salmo salar) cage-farmed in Chile affecting both smolts and adult fish cultured in estuary and marine waters, reaching in some occasions a cumulative mortality up to 25% of the affected population. Diseased fish showed exophthalmia with accumulation of purulent and haemorrhagic fluid around eyes, and ventral petechial haemorrhages. At necropsy, haemorrhage in the abdominal fat, pericarditis, and enlarged liver, spleen and kidney are common pathological changes. Gram-stained smears revealed the presence of Gram-positive cocci, beta-hemolytic, negative for oxidase and catalase tests. Although biochemical characterization of the isolates using the miniaturized system rapid ID 32 Strep suggested their assignation to genus Gemella, sequencing and RFLP analysis of the 16S rRNA revealed that bacteria associated with the mortalities belong to Streptococcus phocae. Serological studies demonstrated that all the salmon isolates are antigenically homogeneous, which can facilitate the development of preventive measures and, although sharing some antigenical determinants, they belong to a different Lancefield group than the type strain isolated from seals. On the basis of these facts, we conclude that the species S. phocae is an emerging pathogen for salmonid culture in Chile, and it should be included as a new member of the warm water streptococcosis.

Primary tuberculosis of the palate.

Tuberculosis (TB) is a life-threatening infectious disease with a high world incidence. However, TB with oral expression is considered rare. The importance of recognising this entity lies in its early diagnosis and treatment, as it can be easily confused with neoplastic or traumatic ulcers. We present a case of a primary TB located in the hard palate and gingiva in an 88-year-old woman.

Oncocytic carcinoma of the parotid gland with late cervical lymph node metastases: a case report.

INTRODUCTION: Oncocytic carcinoma is a rare proliferation of cytomorphologically malignant oncocytes mainly found in glandular tissue, accounting for 0.5% of all epithelial salivary gland malignancies and 0.18% of all epithelial salivary gland tumors. CASE PRESENTATION: We report a case of oncocytic carcinoma arising in the parotid gland of a 65-year-old Caucasian man. Our patient initially underwent left superficial parotidectomy, including the removal of the mass. A close follow-up was made, and four years after first surgery cervical lymph node metastases were confirmed. Therefore, a complete parotidectomy and radical neck dissections were performed. There were no complications and no sign of recurrence after six months of follow-up. CONCLUSION: Oncocytic carcinoma is an extremely rare malignancy in the salivary glands. Prophylactic neck dissection may be indicated for tumors larger than 2 cm in diameter (our patient's tumor was 2.5 cm at its greatest diameter). The clinical course of our patient, with the appearance of cervical lymph node metastases after four years of follow-up, supports this approach. Further investigation of the prognosis and correct treatment of patients with oncocytic carcinoma are required as more cases are reported.

Delirium: A predictor of mortality in the elderly

The frequency of delirium in elderly inpatients is high, resulting in poor hospital outcomes. The objective of this study is to assess whether delirium is an independent predictor for mortality over a three-month period. Methods: Prospective, observational study in a cohort of 171 inpatients aged over 65years. Presence of delirium and/or dementia, severity of delirium and incapacity due to illness were assessed at baseline using DSM-IV diagnostic criteria, the Confusion Assessment Method (CAM), the MMSE, the Delirium Rating Scale (DRS) and the Karnofsky Performance Status (KPS). Mortality rates were evaluated over a three-month follow-up period after enrollment. Kaplan-Meier survival curves were constructed and the adjusted effect of asset of covariates was evaluated with the Cox multiple regression analysis. Results: By 3 months after enrollment, 34.4% of the patients with delirium died, compared with 16.5% of those without delirium. The survival analysis shows a statistically significant difference between the two groups (log-rank=11.92; d.f.=1; P=0.0006). After adjustment for covariates, delirium was found to be independently associated with higher mortality. Conclusions: Delirium was found to be an independent marker for mortality in older medical patients over a three-month follow-up (AU)

Evaluación psiquiátrica transversal en pacientes candidatos a un trasplante cardíaco / Cross-sectional psychiatric evaluation in candidates for heart transplantation

Introducción y objetivos: La enfermedad psiquiátrica en pacientes incluidos en un programa de trasplante cardíaco tiene relación con más mortalidad y morbilidad postrasplante. En este trabajo se analiza la enfermedad psiquiátrica de estos pacientes y el rendimiento de un cuestionario de ansiedad y depresión en enfermos hospitalizados (HAD), y se estudia la relación de los antecedentes clínicos y sociodemográficos con la presencia de enfermedad psiquiátrica. Método: Se realizó un estudio transversal de la enfermedad psiquiátrica en 75 pacientes admitidos en lista de espera del programa de trasplante cardíaco del Hospital Clínic de Barcelona, mediante la entrevista clínica estructurada para el DSM-IV (SCID-IV). Se evaluó sensibilidad, especificidad y valor predictivo positivo (VPP) y negativo (VPN) de la escala autoaplicable de ansiedad y depresión hospitalaria (HAD) en relación con la SCID. Se realizó estadística comparativa mediante la prueba de la *2. Resultados: El 33% de la muestra presentaba enfermedad psiquiátrica en el momento de la evaluación. La subescala de depresión del HAD presenta, respecto de la entrevista SCID, un VPN = 88,3% y la subescala de ansiedad, un VPN = 89,6%. Las variables que se relacionaron con la enfermedad depresiva de forma estadísticamente significativa fueron la evolución de la enfermedad cardíaca > 8 años y presentar un trastorno de la personalidad. Conclusiones: Entre los pacientes candidatos a trasplante cardíaco se da una alta prevalencia de enfermedad psiquiátrica. El HAD descarta con gran fiabilidad a los pacientes sin esas enfermedades. Los factores de vulnerabilidad hacia la enfermedad depresiva son tanto cardiológicos como psiquiátricos

Introduction and objectives: Psychiatric disorders in patients included in a heart transplantation program have predictive value in mortality and posttransplantation morbidity. In this study, we analyzed psychiatric disorders in these candidates and the usefulness of an anxiety and depression rating scale (HAD) in hospitalized patients. We also assessed the association between clinical and sociodemographic history and the presence of psychiatric disorders. Method: A cross-sectional study of psychiatric disorders was performed in 75 patients on the waiting list for heart transplantation at Hospital Clínic in Barcelona. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the self-administered hospital anxiety and depression (HAD) scale were evaluated against a structured clinical interview based on international psychiatric diagnostic criteria (SCID-IV). Statistical comparisons between variables were made through the *2 test. Results: Thirty-three percent of the sample showed psychiatric disorders at evaluation. With respect to the SCID, the depression subscale of the HAD had an NPV of 88.3%, while the anxiety subscale had an NPV of 89.6%. Statistically significant variables associated with depressive disorders were "heart disease duration >8 years" and "presence of a personality disorder". Conclusions: Candidates for heart transplantation have a high prevalence of psychiatric disorders. The HAD was highly reliable in identifying patients without psychiatric disorders. Vulnerability factors for depression include both heart-related and strictly psychiatric aspects

Bioadhesives: a biotechnological opportunity

Marine mussels secrete the byssus in order to attach to solid surfaces and to servive under the turbulent effects of waves. The adhesive responsable for this atachment is the polyphenolic protein secreted by the phenol gland in the foot of the animal To purify this adhesive protein form the chilean mussel Mylilus chilensis, a modification of previous procedures has been developed. Accordingly, the protein is differentially precipitated with acetone in the presence of 0.25 N HCl. The purified protein is rich in the amino acids lysine, 3,4-dihydroxyphenylalanine, serine, threonine, proline and hydrozyproline. The protein exhibited strong adhesion to glass and other solid supports. Moreover, its has been found that the adhesive protein can mediate the immobilization of ß-galactosidase to glass. About 75% of the enzyme activity was immobilized under the experimental conditions described. This is the first study reporting the use of the polyphenolic protein to immobilize enzymes

Actividad física y factores de riesgo cardiovascular y metabólico en la población general / Physical activity and cardiovascular and metabolic risk factors in general population

FUNDAMENTO Y OBJETIVO: Evaluar en un estudio poblacional la asociación entre la actividad física diaria y diferentes factores de riesgo metabólico y cardiovascular. PACIENTES Y MÉTODO: En 1.226 personas (edad: 18-65 años) aleatoriamente seleccionadas en una población del sudeste español se ha evaluado la asociación entre el nivel de actividad física diaria laboral y extralaboral con las siguientes variables: índice de masa corporal, lípidos plasmáticos, presencia de hipertensión arterial, obesidad, glucemia basal alterada y tolerancia anormal de la glucosa. RESULTADOS: La intensidad de la actividad física en el trabajo se correlacionó de manera negativa con las concentraciones de colesterol ligado a lipoproteínas de baja densidad y positivamente con las de colesterol ligado a lipoproteínas de alta densidad. La probabilidad de presentar hipertensión arterial, glucemia basal alterada o tolerancia anormal de la glucosa fue mayor en aquellos que tuvieron una menor actividad física diaria. CONCLUSIONES: La actividad física diaria, considerada como uno de los componentes del estilo de vida, se asocia con la presencia de los componentes del síndrome metabólico. Un aumento de la actividad física diaria debe contribuir a mejorar los patrones favorables a la prevención de los factores de riesgo cardiovascular (AU)