Mortality due to non-AIDS-defining cancers among people living with HIV in Spain over 18 years of follow-up.

PURPOSE: Our aim was to describe non-AIDS-defining cancer (NADC) mortality among people living with HIV (PLWH), to compare it with that of the general population, and to assess potential risk factors. METHODS: We included antiretroviral-naive PLWH from the multicentre CoRIS cohort (2004-2021). We estimated mortality rates and standardised mortality ratios (SMRs). We used cause-specific Cox models to identify risk factors. RESULTS: Among 17,978 PLWH, NADC caused 21% of all deaths observed during the follow-up. Mortality rate due to NADC was 1.58 (95%CI 1.36, 1.83) × 1000 person-years and lung and liver were the most frequent cancer-related causes of death. PLWH had 79% excess NADC mortality risk compared to the general population with the highest SMR found for Hodgkin lymphoma, anal and liver cancers. The SMRs decreased with age and were the highest in age groups under 50 years. The most important prognostic factor was low CD4 count, followed by smoking, viral hepatitis and HIV transmission through heterosexual contact or injection drug use. CONCLUSION: Non-AIDS cancers are an important cause of death among PLWH. The excess mortality related to certain malignancies and the association with immunodeficiency, smoking, and coinfections highlights the need for early detection and treatment of cancer in this population.

How well are we performing the initial assessment of HIV-positive patients? Results from a multicentre cohort in Spain.

OBJECTIVES: The aim of this study was to evaluate adherence to the recommendations of the Spanish guidelines for the initial assessment of patients with HIV infection in the multicentre Cohort of the Spanish HIV/AIDS Network (CoRIS) during the years 2004-2017. METHODS: We calculated the percentage of patients who had each of 11 clinical and analytical recommended examinations performed in their initial evaluation. We evaluated the factors associated with not performing each examination with multivariable logistic regression models. RESULTS: We included 13 612 patients in the study. In the initial assessment, CD4 count and viral load were determined in more than 98.0% of the patients. Serologies for hepatitis A, B and C and syphilis were determined in 55.8%, 66.4%, 89.8% and 81.7% of the patients, respectively. Total cholesterol and creatinine were determined in 78.7% and 78.9% of the patients, respectively. The lowest proportions of examinations were observed for blood pressure, smoking status and latent tuberculosis screening, which were performed in 43.2%, 50.6% and 53.9% of the patients, respectively. Injecting drug users and heterosexual patients (compared to men who have sex with men) and patients with a lower educational level had a higher risk of having an incomplete initial assessment for a substantial number of examinations. Latent tuberculosis screening was less likely in patients with CD4 counts < 200 cells/µL. CONCLUSIONS: The initial assessment of HIV-infected patients is suboptimal for the evaluation of cardiovascular risk, smoking status, screening of syphilis and viral hepatitis, and diagnosis of latent tuberculosis: adherence to the guidelines was low for these examinations.

Gene expression differences in primary colorectal tumors and matched liver metastases: chemotherapy related or tumoral heterogeneity?

BACKGROUND: Treatment of metastatic colorectal cancer (mCRC) is generally based on genetic testing performed in primary tumor biopsies, but whether the genomic status of primary tumors is identical to that of metastases is not well known. We compared the gene expression profiles of formalin-fixed paraffin-embedded (FFPE) biopsies of colorectal primary tumors and matched liver metastases. PATIENTS AND METHODS: We compared the expression of 18 genes in FFPE CRC tumors and their matched liver metastases from 32 patients. The expression of each gene in CRC primary tumors and their matched liver metastases was tested using Student's t test for paired samples. Pairwise correlations of each gene in the primary tumors and matched liver metastases were evaluated by Pearson's correlation coefficient. RESULTS: The expression of six genes was significantly different in primary tumors compared with their matched liver metastases [CXCR4 (p < 0.001), THBS1 (p = 0.007), MMP 9 (p = 0.048), GST Pi (p = 0.050), TYMP (p = 0.042) and DPYD (p < 0.001)]. For the remaining genes, where no significant differences were observed, only SMAD4 (r s = 0.447, p = 0.010), ERCC1 (r s = 0.423, p = 0.016) and VEGF A (r s = 0.453, p = 0.009) showed significant correlation in expression between the two tissues. Therefore, we only detected similar gene expression levels between the tumor and the metastases in these three markers. CONCLUSIONS: We only found similar gene expression levels between the tumor and the metastases in three genes (SMAD4, ERCC1, and VEGF A). However, our study could not assess whether the differences in gene expression were secondary to tumoral heterogeneity or to molecular changes induced by previous chemotherapy.

SMAD4 and TS expression might predict the risk of recurrence after resection of colorectal liver metastases.

PURPOSE: Colorectal liver metastases (CLM) have significant molecular heterogeneity, which contributes to the risk of recurrence following surgery. Most of the traditional scores intended to predict recurrence is based on clinicopathological variables and it is unclear whether incorporating molecular biomarkers might improve our assessment of the risk of recurrence. Our aim was to determine if molecular biomarkers might be associated with the risk of recurrence after surgery of CLM. PATIENTS AND METHODS: A total of 121 patients diagnosed with colorectal cancer (CRC) with resected liver metastases were included. The role of several clinicopathological variables to predict patient's outcome after resection of liver metastases was analyzed. Eighteen genes related to CRC pathogenesis were also included in the analyses. Univariate and multivariate stepwise Cox regression analyses were performed to identify factors associated with recurrence and the risk of death. RESULTS: Eight prognostic factors for progression-free survival and nine factors for overall survival were identified in the univariate analyses. After adjusting for other risk factors, only the expression of two molecular factors was associated with the risk of recurrence: TS (HR 0.631, 95 % CI 0.422-0.944) and SMAD4 (HR 1.680, 95 % CI 1.047-2.695). None of the variables was significantly associated with the risk of death in the multivariate analyses. CONCLUSIONS: The prognostic significance of most traditional clinicopathological variables might be insufficient to define patients at risk for recurrence after liver metastases resection. Molecular biomarkers might improve the identification of patients with higher risk of recurrence.

[Clinical-biological and radiological study of Wegener's granulomatosis in a university hospital]. / Estudio clínico-biológico y radiológico de la granulomatosis de Wegener en un hospital universitario.

UNLABELLED: Wegener's granulomatosis is a rare systemic vasculitis that fundamentally affects the kidney and respiratory tract. Although the histological findings are very characteristic, they do not occur in all cases, which makes diagnosis difficult. METHODS: The main clinical, biological and radiological characteristics of 13 cases of Wegener's granulomatosis diagnosed in a university hospital of the center of Spain are collected in this present paper. RESULTS: The majority of the patients were men in their 50's. Fever and general syndrome were usual presentations of the disease. Upper respiratory tract (10 cases) and lung involvement (9), followed by renal involvement (8), were the most common. Alveolar infiltrates and bilateral nodules were the most common findings in the X-ray and thoracic CT scan, although the latter permits a greater definition of the lesions. Measurement of antibodies against cytoplasma of the neutrophils (ANCA) was positive in 8 patients (6 cANCA and 2 pANCA). Renal biopsy was used most for the histologic diagnosis, where focal and segmental glomerulonephritis was the most common finding. The majority of the patients received steroids plus cyclophosphamide as induction treatment. CONCLUSIONS: Wegener's disease is a rare systemic vasculitis. The existence of hematuria or respiratory tract involvement in a patient with fever suggests the diagnosis. Conducting a CT scan and ANCAs measurement are useful tools for its diagnosis, since the histology is not definitive.

[Homocysteine. The cardiovascular risk factor of the next millennium?]. / La homocisteína. El factor de riesgo cardiovascular del próximo milenio?

Several epidemiologic studies have demonstrated that hyperhomocysteinemia is a risk factor for arteriosclerosis in coronary, cerebral, peripheral and aortic arteries. This risk is independent of other cardiovascular risk factors, and it is dose related. However, prospective studies show contradictory findings. Hyperhomocysteinemia is also associated with a higher risk of venous thrombosis to which other coagulation disorders, such as factor V Leiden, could contribute. Hyperhomocysteinemia can be due to genetic defects in the enzymes that control homocysteine metabolism, and also to other factors, mainly nutritional (deficiencies in vitamin B6, vitamin B12, or folic acid). Dietary supplements of these vitamins reduce plasma homocysteine levels. Randomized clinical trials are still needed to demonstrate that reducing plasma homocysteine levels will reduce the risk for cardiovascular disease.

[Churg-Strauss syndrome. Our experience in 2 decades]. / Síndrome de Churg-Strauss. Nuestra experiencia en dos décadas.

BACKGROUND: Since 1951, the year when the Churg-Strauss syndrome was reported, several isolated cases have been reported in the literature but works containing a high number of cases are exceptional. The features of the syndrome as well as diagnostic criteria have not been contrasted in large series. We therefore tried to analyze these parameters in 16 patients diagnosed of Churg-Strauss syndrome at our hospital. METHODS: A retrospective analysis was made of 16 patients diagnosed of Churg-Strauss syndrome at Hospital Universitario La Paz from 1978 at 1998. Data regarding personal antecedents, clinical manifestations, analytical parameters, histology and clinical course were collected. Also, the main diagnostic criteria reported in the literature were applied to each case. RESULTS: Of the 16 cases, thirteen (81%) were women, six were diagnosed at an age between 21 and 40 years; other six cases from 51 to 70 years. All patients had antecedents of bronchial asthma. Among clinical manifestations, 60% had fever and 50% a general syndrome. The main involved organs by decreasing frequency were lung (100%), nervous system (63%), and heart (44%). The mean eosinophilic count was 7,640/mm3. The histological diagnosis was obtained in 14 out of the 16 patients (88%). The most efficient biopsies corresponded to muscle and nerve. After therapy, no relapse was noted of vasculitis although bronchial asthma persisted in most patients (12). Twelve cases (75%) fulfilled the Lanham diagnostic criteria. CONCLUSIONS: Churg-Strauss syndrome affects mainly women with severe eosinophilia. Electromyogram and muscle and peripheral nerve biopsy are useful tools for diagnosis. The Lanham criteria lead to the diagnosis in most patients.