Impact of influenza related hospitalization in Spain: characteristics and risk factor of mortality during five influenza seasons (2016 to 2021).

Background: Estimating the global influenza burden in terms of hospitalization and death is important for optimizing prevention policies. Identifying risk factors for mortality allows for the design of strategies tailored to groups at the highest risk. This study aims to (a) describe the clinical characteristics of hospitalizations with a diagnosis of influenza over five flu seasons (2016-2017 to 2020-2021), (b) assess the associated morbidity (hospitalization rates and ICU admissions rate), mortality and cost of influenza hospitalizations in different age groups and (c) analyze the risk factors for mortality. Methods: This retrospective study included all hospital admissions with a diagnosis of influenza in Spain for five influenza seasons. Data were extracted from the Spanish National Surveillance System for Hospital Data from 1 July 2016 to 30 June 2021. We identified cases coded as having influenza as a primary or secondary diagnosis (International Classification of Diseases, 10th revision, J09-J11). The hospitalization rate was calculated relative to the general population. Independent predictors of mortality were identified using multivariable logistic regression. Results: Over the five seasons, there were 127,160 hospitalizations with a diagnosis of influenza. The mean influenza hospitalization rate varied from 5/100,000 in 2020-2021 (COVID-19 pandemic) to 92.9/100,000 in 2017-2018. The proportion of influenza hospitalizations with ICU admission was 7.4% and was highest in people aged 40-59 years (13.9%). The case fatality rate was 5.8% overall and 9.4% in those aged 80 years or older. Median length of stay was 5 days (and 6 days in the oldest age group). In the multivariable analysis, independent risk factors for mortality were male sex (odds ratio [OR] 1.14, 95% confidence interval [95% CI] 1.08-1.20), age (<5 years: OR 1; 5-19 years: OR 2.02, 95%CI 1.17-3.49; 20-39 years: OR 4.11, 95% CI 2.67-6.32; 40-59 years: OR 8.15, 95% CI 5.60-11.87; 60-79 years: OR 15.10, 95% CI 10.44-21.84; ≥80 years: OR 33.41, 95% CI 23.10-48.34), neurological disorder (OR 1.97, 95% CI 1.83-2.11), heart failure (OR 1.85, 95% CI 1.74-1.96), chronic kidney disease (OR 1.33, 95% CI 1.25-1.41), chronic liver disease (OR 2.95, 95% CI 2.68-3.27), cancer (OR 1.85, 95% CI 1.48-2.24), coinfection with SARS-CoV2 (OR 3.17, 95% CI 2.34-4.28), influenza pneumonia (OR 1.76, 95% CI 1.66-1.86) and admission to intensive care (OR 7.81, 95% CI 7.31-8.36). Conclusion: Influenza entails a major public health burden. People aged over 60-and especially those over 80-show the longest hospital stays. Age is also the most significant risk factor for mortality, along with certain associated comorbidities.

Predictive model of resection in endoscopic endonasal approach for pituitary adenomas based on anatomical limits.

INTRODUCTION: The aim of this project is to study several anatomical-radiological features of pituitary adenomas obtained from preoperative radiological images and to analyze their relationship with the extent of resection achieved through the endoscopic endonasal approach. The second objective was to create a prediction model of the extent of resection. MATERIAL AND METHODS: We retrospectively evaluated 105 patients. Tumor volume, Knosp grade, suprasellar-diaphragm coefficient and invasion of the posterior compartment have been analyzed. The extent of resection was assessed by analyzing the postoperative magnetic resonance. We created the predictive scale using statistically independent variables. RESULTS: When each of the variables has been studied individually, a statistically significant value of all of them is appreciated to obtain a complete resection. However, only the Knosp grade and the suprasellar-diaphragm coefficient had a statistically significant value as independent variables. The sum of the Odds Ratio obtained from the Knosp scale, and the suprasellar-diaphragm coefficient gives the probability of complete resection. A new set of cases was employed to validate the scale. CONCLUSIONS: The cavernous sinus invasion and the newly designed suprasellar diaphragm coefficient are directly related to the extent of resection in pituitary adenoma surgery performed by a transellar endoscopic approach. Moreover, based on both radiologic factors, a predictive scale may predict the probability of complete resection in a series of patients.

Three-Dimensional Reconstruction of the Sphenoid Sinus Anatomy for Presurgical Planning with Free OSIRIX Software.

Background A preoperative three-dimensional (3D) surgical field understanding remains a key factor to achieve safer endonasal transsphenoidal endoscopic approaches (ETSE). The aim of this article is to describe how we can get a reliable 3D sphenoidal anatomical reconstruction for surgical planning by using a user-friendly, accurate, and free image software. Methods Free computer software (OSIRIX Medical Imaging Software) was used to create in a personal computer a three-dimensional (3D) reconstruction of the sphenoid sinus (SS) based on head computed tomography angiographies (CTAs) from a series of 67 patients who were operated for sellar tumors during a 4-year period (March 2016 to March 2020). The aim of the 3D reconstruction with OSIRIX was to reveal preoperatively the most important intrasphenoidal structures seen from the endonasal point of view. Results The intraoperative visible sphenoidal structures were previously recognized in the virtual 3D reconstructed image with 100% of specificity (SP) and positive predictive value. The OSIRIX view by using region of interest points allowed us to see preoperatively the internal carotid artery parasellar course even in those cases in which it was hidden by bone or tumor. Moreover, the 3D reconstruction was able to provide a clear differentiation between the tumor and the pituitary gland when both structures were in contact with the sellar floor. Conclusion Our experience with the OSIRIX software from CTA as preoperative planning for endonasal pituitary surgery was valuable, because it gave us access in simple way to a free and reliable 3D image of the SS.

SARS-CoV-2 Omicron BA.1 variant breakthrough infections in nursing home residents after an homologous third dose of the Comirnaty® COVID-19 vaccine: Looking for correlates of protection.

We investigated whether peripheral blood levels of SARS-CoV-2 Spike (S) receptor binding domain antibodies (anti-RBD), neutralizing antibodies (NtAb) targeting Omicron S, and S-reactive-interferon (IFN)-γ-producing CD4+ and CD8+ T cells measured after a homologous booster dose (3D) with the Comirnaty® vaccine was associated with the likelihood of subsequent breakthrough infections due to the Omicron variant. An observational study including 146 nursing home residents (median age, 80 years; range, 66-99; 109 female) evaluated for an immunological response after 3D (at a median of 16 days). Anti-RBD total antibodies were measured by chemiluminescent immunoassay. NtAb were quantified by an Omicron S pseudotyped virus neutralization assay. SARS-CoV-2-S specific-IFNγ-producing CD4+ and CD8+ T cells were enumerated by whole-blood flow cytometry for intracellular cytokine staining. In total, 33/146 participants contracted breakthrough Omicron infection (symptomatic in 30/33) within 4 months after 3D. Anti-RBD antibody levels were comparable in infected and uninfected participants (21 123 vs. 24 723 BAU/ml; p = 0.34). Likewise, NtAb titers (reciprocal IC50 titer, 157 vs. 95; p = 0.32) and frequency of virus-reactive CD4+ (p = 0.82) and CD8+ (p = 0.91) T cells were similar across participants in both groups. anti-RBD antibody levels and NtAb titers estimated at around the time of infection were also comparable (3445 vs. 4345 BAU/ml; p = 0.59 and 188.5 vs. 88.9; p = 0.70, respectively). Having detectable NtAb against Omicron or SARS-CoV-2-S-reactive-IFNγ-producing CD4+ or CD8+ T cells after 3D was not correlated with increased protection from breakthrough infection (OR, 1.50; p = 0.54; OR, 0.0; p = 0.99 and OR 3.70; p = 0.23, respectively). None of the immune parameters evaluated herein, including NtAb titers against the Omicron variant, may reliably predict at the individual level the risk of contracting COVID-19 due to the Omicron variant in nursing home residents.

Teledermatology in paediatrics: Health-care impact on the early treatment of infantile haemangiomas.

INTRODUCTION: Teledermatology can solve diagnostic and therapeutic problems in paediatrics, for example in infantile haemangiomas (IHs) requiring early treatment with propranolol. This study aims to assess the impact of teledermatology following its implementation in a health area of Spain, specifically analysing its effectiveness in reducing the age of first propranolol treatment for IH. METHODS: This was a descriptive study of paediatric teledermatology from 2015 to 2018, studying age, sex, diagnosis, time and mode of resolution. All IHs referred via teledermatology were analysed, and age at propranolol initiation was compared to the period prior to implementation (2008-2014). We also analysed IHs according to referral pathways (teledermatology vs. conventional pathways). RESULTS: We included 432 consultations (47.7% boys). The main diagnoses were IH, erythematous-desquamative diseases and infections. Concordance in diagnosis between paediatricians and dermatologists was good, and 48.12% of cases consulted via teledermatology were resolved remotely. Response time was 2.81 days on average. Children younger than two months of age showed the highest proportion of in-person visits. In 2015-2018, children with IHs began treatment with propranolol at a mean age of 4.5 months (1.9 months in those referred via teledermatology vs. 5.6 months in those using conventional referral pathways). In 2008-2014, the mean age at referral was 7.1 months. These differences were significant. DISCUSSION: Teledermatology is a fast and effective tool to resolve paediatric cases, enabling a significant decrease in the age of treatment in infants with IH.

Experience with tocilizumab in severe COVID-19 pneumonia after 80 days of follow-up: A retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and predictors of major outcomes in patients treated with tocilizumab (TCZ) for severe COVID-19 pneumonia. PATIENTS AND METHODS: Case series of all sequential patients with severe COVID-19 pneumonia treated with TCZ at an Academic Spanish hospital (March 12 - May 2, 2020). Clinical outcomes: death, length of hospital stay. An early clinical response to TCZ (48-72 h after the administration) was assessed by variations in respiratory function markers, Brescia COVID Respiratory Severity Scale (BCRSS), inflammatory parameters, and patients' and physicians' opinion. Associations were tested by multiple logistic regression. RESULTS: From a cohort of 236 patients, 77 patients treated with TCZ were included (median age 62 years (IQR 53.0-72.0), 64.9% were males), 42.9% had Charlson index ≥3; hypertension (41.6%), obesity (34.7%), and diabetes (20.8%). Median follow-up was 83.0 days (78.0-86.5), no patient was readmitted. ICU admission was required for 42 (54.5%), invasive mechanical ventilation in 38 (49.4%) and 10 patients died (12.9% global, 23.8% at ICU admitted). After multivariate adjustment, TCZ response by BCRSS (OR 0.03 (0.01-0.68), p = 0.028), and Charlson index (OR 3.54 (1.20-10.44), p = 0.022) has been identified as independent factors associated with mortality. Median of hospital stay was 16.0 days (11.0-23.0); BCRSS, physician subjective and D-dimer response were associated with shorter hospitalization stay. CONCLUSIONS: In a Mediterranean cohort, use of tocilizumab for severe COVID-19 show 12.9% of mortality. Early TCZ-response by BCRSS and low comorbidity were associated with increased survival. Early TCZ-response was related to shorter median hospital stay.

Heterogeneity in the linear shiny white structures in melanomas seen with polarized light according to histopathological association: Cross-sectional observational study in 118 cutaneous melanomas.

Polarized dermoscopy enables visualization of linear shiny white structures in melanomas, thought to be due to the existence of fibrosis in the dermis. Our objective was to establish the existence of two types of linear shiny white structures and assess their association with different histological structures. We performed a cross-sectional study including all non-acral, non-facial melanomas from our hospital with linear shiny white structures. The outcome variable was the type of linear shiny white structures: shiny white streaks and white strands. We evaluated their association with explanatory variables that may affect the reflectance of melanomas and Breslow index. We used χ2 statistics and also calculated the sensitivity and specificity of each linear shiny white structure to predict those variables. We detected linear shiny white structures in 118 melanomas. Regarding shiny white streaks, we only found a statistically significant positive relationship with fibrosis in the papillary dermis. Regarding white strands, we found statistically significant and positive relationships with hyperkeratosis, Breslow index of 0.8 mm or more and acanthosis. Sensitivity and specificity study revealed that the presence of shiny white streaks was the most sensitive (81.7%) and specific (72.3%) for fibrosis in the papillary dermis, and presence of white strands was the most sensitive (91.1%) and specific (85.7%) for hyperkeratosis.

The influence of information on the prevention of occupational risks and ergonomic requirements in the development of non-traumatic osteomuscular diseases of the shoulder - a pilot study.

OBJECTIVES: Shoulder pain associated with upper limb musculoskeletal disorders is an important health problem in clinical practice due to its high prevalence, frequent consultations in primary healthcare and occupational health. Preventive strategies, including information disseminated among workers, can be useful. The aim of this study is to analyze the associations between non-traumatic osteomuscular diseases of the shoulder and the workers' knowledge of the risks at the workplace and preventive measures developed there, as well as the association with ergonomic requirements. MATERIAL AND METHODS: An observational case-control study was carried out on an occupationally active population assisted during 1 year in 1 healthcare center, involving 690 participants. Data were collected through a questionnaire including sociodemographic variables, the workplace, the knowledge of prevention and ergonomic requirements. The independent effect of the variables associated with non-traumatic shoulder pathology was explored through logistic regression. RESULTS: In total, 66.7% of the participants stated that they had been informed of the occupational hazards related to their jobs. The following variables were associated with a lower probability of shoulder injuries: male gender, working hours > 9 h/day or > 40 h/week, as well as having information on the risks associated with the workplace, using personal protective equipment, the existence of an occupational risks prevention service and/or risk assessment, the knowledge of the prevention plan, periodic medical examinations, and using one arm or physical force at work. A multivariate analysis revealed that the risk increased with age and lower educational levels, forced postures, repeated gestures, monotony and temporary absences from work. Furthermore, being informed of workplace risks, and using a single arm as well as physical force were shown as independent protective factors. CONCLUSIONS: Information on both the ergonomic requirements and how to prevent occupational risks is a useful tool for the prevention of non-traumatic shoulder diseases. Preventive policies including health education interventions in the workplace could benefit other developed preventive activities. Int J Occup Med Environ Health. 2019;32(6):825-40.

Best Protocol for Combined Contrast-Enhanced Thoracic and Abdominal CT for Lung Cancer: A Single-Institution Randomized Crossover Clinical Trial.

OBJECTIVE: The purpose of this study was to evaluate the superiority of either of two protocols for combined contrast-enhanced thoracic and abdominal CT of patients with lung cancer by comparing contrast enhancement, contrast-related artifacts, image quality, and radiation dose. SUBJECTS AND METHODS: In this randomized controlled crossover clinical trial, 77 patients who underwent 203 CT examinations were enrolled. All patients underwent at least two examinations performed with both protocols. Protocol A consisted of two acquisitions: one 35-second delayed CT acquisition for the chest followed by a 70-second delayed abdominal acquisition. Protocol B was a single 60-second delayed acquisition covering the chest and the abdomen. Attenuation and noise of the aorta, pulmonary artery, and liver were measured. Contrast-related artifacts, mediastinal lymph node visualization, liver enhancement, and noise were visually scored. Dose-length product was recorded. Statistical analysis was performed by t and chi-square tests and kappa statistics. RESULTS: Contrast-related artifacts were more severe at all evaluated levels, and visualization of lymph node regions was statistically significantly worse with protocol A. There were no differences in enhancement or noise score of the liver. Tumor delineation and pleural findings were better evaluated with delayed phase images. Dose-length product was significantly higher with protocol A (645.0 vs 521.5 mGy · cm; p < 0.0001). CONCLUSION: A single 60-second delayed acquisition for thoracic and abdominal contrast-enhanced CT is associated with less contrast artifact and affords better visualization of lymph nodes at a lower radiation dose while acceptable vascular and hepatic contrast enhancement is maintained.

Subclinical atherosclerosis in low Framingham risk HIV patients.

BACKGROUND: Pathogenesis of atherosclerosis is complex, and differences between HIV-infected patients and general population cannot be completely explained by the higher prevalence of traditional cardiovascular risk factors. We aimed to analyse the association between inflammation and subclinical atherosclerosis in HIV patients with low Framingham risk score. MATERIALS AND METHODS: Case-control study. SETTING: Outpatient Infectious Diseases clinic in a university hospital. SUBJECTS: HIV-1-infected patients aged > 35 years receiving antiretroviral treatment with viral load < 50 copies/mL and Framingham risk score < 10%. EXCLUSION CRITERIA: inflammatory diseases; dyslipidaemia requiring statins; smoking > 5 cigarettes/day; diabetes; hypertension; vascular diseases. MAIN OUTCOME: subclinical atherosclerosis determined by ultrasonography: common carotid intima-media thickness greater than 0·8 mm or carotid plaque presence. Explanatory variables: ribosomal bacterial DNA (rDNA), sCD14, interleukin-6 (IL-6) and TNF-α. RESULTS: Eighty-four patients were included, 75% male, mean age 42 years and mean CD4+ cells 657 ± 215/mm3 . Median Framingham risk score was 1% at 10 years (percentile 25-75: 0·5-4%). Eighteen patients (21%) had subclinical atherosclerosis; the associated factors were older age (P = 0·001), waist-hip ratio (P = 0·01), time from HIV diagnosis (P = 0·02), rDNA (P = 0·04) and IL-6 (P = 0·01). In multivariate analysis, OR for subclinical atherosclerosis was 7 (95% CI, 1.3-40, P = 0.02) and 9 (95% CI, 1.0-85, P = 0.04) for patients older than 44 years and IL-6 > 6·6 pg/mL, respectively. CONCLUSIONS: Well-controlled HIV patients with low Framingham risk score have a high prevalence of subclinical carotid atherosclerosis, and the main risk factors are age and inflammation. These patients are not receiving primary prophylaxis for cardiovascular events according to current guidelines.

Does the Type of Surgical Approach and the Use of Uterine Manipulators Influence the Disease-Free Survival and Recurrence Rates in Early-Stage Endometrial Cancer?

OBJECTIVE: The purpose of this study was to compare the long-term safety, disease-free survival, and recurrence rate of total laparoscopic hysterectomy using uterine manipulator and abdominal hysterectomy in the surgical treatment in early-stage endometrial cancer. STUDY DESIGN: This was a cohort study of 147 patients with clinical endometrial cancer (laparoscopic surgery group, 77 women; laparotomy group, 70 women). Data were evaluated and analyzed by intention-to-treat principle, and survival data of stage I endometrial cancer (129 patients; 66 from laparoscopic surgery group and 60 from laparotomy group) were estimated by using the Kaplan-Meier curves. RESULTS: After a follow-up period of 60 months for both laparoscopic surgery and laparotomy groups, no significant difference in the cumulative recurrence rates (7.4% and 13.1%, P = 0.091) and overall survival (97.1% and 95.1%, P = 0.592) was detected between both groups of stage I endometrial cancer. Conversion to laparotomy occurred in 10.4% (8/77) of the laparoscopic procedures. Laparoscopic hysterectomy was associated with less use of pain medication (P = 0.001) and a shorter hospital stay (P < 0.001), but the procedure took longer than laparotomic hysterectomy (P < 0.001). The proportion of patients with intraoperative and long-term complications was not significantly different between both groups. The use of uterine manipulators did not have increased recurrence rate in patients treated with laparoscopic approach. CONCLUSIONS: The laparoscopic surgery approach to early-stage endometrial cancer using uterine manipulators is as safe and effective as the laparotomic approach.

Osteopontin Regulates VEGFA and ICAM-1 mRNA Expression in Breast Carcinoma.

OBJECTIVES: To analyze the regulatory role of osteopontin on biomarkers associated with cell survival, invasiveness, and angiogenesis mechanisms in a clinical series and breast cancer cell lines. METHODS: We analyzed by quantitative real-time polymerase chain reaction the messenger RNA (mRNA) expression of osteopontin, Bcl2, intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor A (VEGFA) in several breast cancer cell lines and in 148 breast carcinomas classified into intrinsic subtypes. RESULTS: We found coexpression of osteopontin, Bcl2, ICAM-1, and VEGFA in triple-negative MDA-MB-468 and MDA-MB-231 cell lines. Furthermore, osteopontin silencing by small interfering RNA inhibited ICAM-1 and VEGFA expression and cell proliferation in MDA-MB-468 cells. In breast cancer specimens, we found a positive correlation between osteopontin, ICAM-1, and VEGFA mRNA expression, especially in triple-negative/basal-like tumors. Among patients with osteopontin-overexpressing tumors, VEGFA remained an independent prognostic indicator for recurrence (hazard ratio, 2.95; 95% confidence interval [CI], 1.48-5.87; P = .002) and death (hazard ratio, 3.25; 95% CI, 1.48-7.11; P = .003) (multivariate analysis, Cox regression). CONCLUSIONS: Our results support that osteopontin regulates ICAM-1 and VEGFA expression mainly in triple-negative/basal-like breast carcinomas, suggesting a relevant role in the pathogenesis and tumor progression of this molecular subtype. Moreover, VEGFA mRNA levels showed an independent prognostic value in patients with breast cancer.

Vitamin D insufficiency and subclinical atherosclerosis in non-diabetic males living with HIV.

INTRODUCTION: Vitamin D insufficiency (VDI) has been associated with increased cardiovascular risk in the non-HIV population. This study evaluates the relationship among serum 25-hydroxyvitamin D [25(OH)D] levels, cardiovascular risk factors, adipokines, antiviral therapy (ART) and subclinical atherosclerosis in HIV-infected males. METHODS: A cross-sectional study in ambulatory care was made in non-diabetic patients living with HIV. VDI was defined as 25(OH)D serum levels <75 nmol/L. Fasting lipids, glucose, inflammatory markers (tumour necrosis factor-α, interleukin-6, high-sensitivity C-reactive protein) and endothelial markers (plasminogen activator inhibitor-1, or PAI-I) were measured. The common carotid artery intima-media thickness (C-IMT) was determined. A multivariate logistic regression analysis was made to identify factors associated with the presence of VDI, while multivariate linear regression analysis was used to identify factors associated with common C-IMT. RESULTS: Eighty-nine patients were included (age 42 ± 8 years), 18.9% were in CDC (US Centers for Disease Control and Prevention) stage C and 75 were on ART. VDI was associated with ART exposure, sedentary lifestyle, higher triglycerides levels and PAI-I. In univariate analysis, VDI was associated with greater common C-IMT. The multivariate linear regression model, adjusted by confounding factors, revealed an independent association between common C-IMT and patient age, time of exposure to protease inhibitors (PIs) and impaired fasting glucose (IFG). In contrast, there were no independent associations between common C-IMT and VDI or inflammatory and endothelial markers. CONCLUSIONS: VDI was not independently associated with subclinical atherosclerosis in non-diabetic males living with HIV. Older age, a longer exposure to PIs, and IFG were independent factors associated with common C-IMT in this population.

Association of increased osteopontin and splice variant-c mRNA expression with HER2 and triple-negative/basal-like breast carcinomas subtypes and recurrence.

Osteopontin, a secreted phosphoglycoprotein, promotes tumor progression through binding to integrins and CD44 cell receptors. Its overexpression has been correlated with metastasis and adverse outcome in several neoplasms. In breast carcinoma, osteopontin mRNA and its splicing variant-c, a suggested marker for transformed cells, have not been extensively analyzed. Immunohistochemistry was performed in 415 breast carcinomas to examine total osteopontin and osteopontin-c protein distribution. RNA was extracted and retrotranscribed to cDNA from 309 tumors classified into immunophenotypes and in six cell lines representing the breast cancer subtypes. Total osteopontin and osteopontin-c mRNA levels were measured by quantitative RT-polymerase chain reaction. The median fold change of total osteopontin mRNA was higher in HER2-positive (fold-change = 14.7) and triple-negative/basal-like (fold-change = 14.7) tumors, whereas osteopontin-c mRNA was elevated in triple-negative/basal-like subtype (fold-change = 2.8). Total osteopontin levels were increased in SK-BR-3 (HER2-positive) and MDA-MB-468 (triple-negative/basal-like) cell lines. Higher total and osteopontin-c mRNA levels were seen in tumors of high grade, with necrosis, positive nodal status and high Nothingam Prognostic Index score. Disease-free survival was significantly shorter for patients whose tumors overexpressed total osteopontin (67% vs 73%). Moreover, increased osteopontin-c stratified subgroups of patients at higher risk of recurrence among immunophenotypes, especially in triple-negative/basal-like subtype (70% vs 83%). By multivariate analyses for disease-free survival, osteopontin-c emerged as a significant predictor of relapse. In summary, our data showed an association of osteopontin with poor prognostic factors, aggressive subtypes HER2 and triple-negative/basal-like, and higher risk of recurrence.

[Association between inflammatory markers and microbial translocation in patients with human immunodeficiency virus infection taking antiretroviral treatment]. / Asociación entre marcadores inflamatorios y traslocación bacteriana en pacientes con infección por el virus de la inmunodeficiencia humana en tratamiento antirretroviral.

BACKGROUND AND OBJECTIVE: Inflammatory biomarkers are increased in patients with human immunodeficiency virus (HIV) infection. Antiretroviral treatment (ART) improves some parameters but do not normalize them. The aim of this study is to determine those factors (including microbial translocation) associated with higher inflammation in HIV treated patients. PATIENTS AND METHODS: Transversal observational study. INCLUSION CRITERIA: HIV patients receiving ART with an HIV viral load (VL)<400 copies/mL. Selection of patients: consecutively between November 2011 and January 2012. Main variable: plasma levels of interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). Main explanatory variable: microbial translocation markers (16S ribosomal DNA and sCD14). Patients with IL-6 or TNF-α levels above percentile 75 (group 1) were compared with the rest of patients (group 2). Odds ratio (OR) were determined. RESULTS: Eighty-one patients were included (73% male, median age 45 years, 48% stage C). Twenty-six percent had chronic hepatitis C. Median CD4 cell was 493/mm(3) and 30% had detectable HIV VL. 16S ribosomal DNA was detected in 21% of patients. Factors associated with the higher levels of inflammatory markers were 16S ribosomal DNA (OR 77, P<.0001), sCD14 levels (P<.0001) and history of cardiovascular disease (OR 15, P<.01). In multivariate analysis, associations remained for 16S ribosomal DNA (OR 62, P<.0001) and previous cardiovascular disease (OR 25, P<.01). CONCLUSIONS: In patients with HIV infection receiving treatment, the higher levels of inflammatory markers are associated with microbial translocation and past cardiovascular events.

Association of mammalian target of rapamycin with aggressive type II endometrial carcinomas and poor outcome: a potential target treatment.

The classification of endometrial carcinoma divided into types I and II has shown clinical usefulness. Molecular alterations of PTEN and Wnt/ß-catenin have been identified in this neoplasia. However, the role of mammalian target of rapamycin according to subcellular localization in the pathogenesis of this neoplasia and its prognostic significance are not well defined. We studied the expression of phosphorylated mammalian target of rapamycin, PTEN, and ß-catenin and their relationship with clinicopathologic features, molecular factors (microsatellite instability, mismatch repair, and BRAF genes) and patients' survival in a series of 260 nonconsecutive endometrial carcinomas. Tissue microarrays were manually constructed, and genomic DNA was extracted from paraffin-embedded cylinders (1 mm thick) from preselected tumor areas. The mammalian target of rapamycin in the nuclei (mTORC2; 47%) or cytoplasm (mTORC1; 48%) were seen in type II endometrial carcinoma, the latter also in advanced stages (P ≤ .046). PTEN loss (58%) was detected in type I endometrial carcinoma of grade 1, at early stage, with mismatch repair gene loss (24.4%) and microsatellite instability-positive status (22%; P ≤ .05). Nuclear ß-catenin (16%) was found in type I tumors of younger patients (P ≤ .003). In contrast, BRAF-V600E mutations were not detected (0%). Mammalian target of rapamycin cytoplasmic high expression implied poorer prognosis (P = .02; Kaplan-Meier, log-rank test), but grade 3 tumors, vascular invasion, advanced stage, or PTEN presence correlated independently with a negative impact on survival (all P ≤ .036; Cox analysis). Our results show that mammalian target of rapamycin, PTEN, and ß-catenin are independently involved in different molecular subtypes of endometrial carcinoma with diverse patients' prognosis and support their distinctive treatment based on targeted drugs.

Low-level HIV viremia is associated with microbial translocation and inflammation.

BACKGROUND: Decrease in HIV viral load (VL) is accompanied by decrease in microbial translocation (MT) and chronic inflammation, but the behavior of these markers in patients with HIV-VL <20 copies per milliliter is unknown. The aim of this study was to determine whether strict control of HIV-VL is associated with MT and chronic inflammation. METHODS: Observational cross-sectional study. INCLUSION CRITERIA: HIV patients receiving antiretroviral therapy and HIV-VL <200 copies per milliliter for more than 6 months. EXCLUSION CRITERIA: chronic liver disease, active infection, or antibiotic consumption. Recruitment: patients who consecutively visited the outpatient clinic in November 2011. Primary endpoint: molecular MT as determined by detection in plasma of 16S ribosomal DNA. Secondary variables: lipopolysaccharide, soluble CD14, tumor necrosis factor α, and interleukin 6. Primary explanatory variable: HIV-VL (COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0) with a detection limit of 20 copies per milliliter. RESULTS: Fifty-two patients were included: 65% men, median age 45 years, HIV acquired predominantly through sex (75%), 40% Centers for Disease Control and Prevention stage C, and median CD4 lymphocyte count 552 cells per cubic millimeter (range, 126-1640 cells/mm). Molecular MT was observed in 46% and 18% of patients with low-level (20-200 copies/mL) and negative (<20 copies/mL) HIV-VL, respectively (P < 0.05). Plasma levels of inflammatory markers (tumor necrosis factor α and interleukin 6) were higher in patients with molecular MT (P < 0.01) and were not influenced for HIV-VL. CONCLUSIONS: Patients with HIV infection receiving treatment and negative HIV-VL (<20 copies/mL) present less frequently MT than patients with low-level HIV viremias (20-200 copies/mL). MT is associated with higher levels of inflammation markers, independent of HIV-VL.

[Do differences exist in the neurosurgical handling of intracranial lesions of pregnant patient? Outcomes of our experience and literature review]. / ¿Existen diferencias en el manejo neuroquirúrgico de las lesiones intracraneales en la paciente gestante? Resultados de nuestra experiencia y revisión de la literatura.

OBJECTIVE: The main objective of our work is to revise our neurosurgical experience in pregnant patient and to carry out a revision of the related literature in order to optimize the neurosurgical handling of these kind of patients. METHOD: Retrospective study between august 1993 and June 2010. We included patients who were pregnant at the time and who presented any trace of cranial neurosurgical or spinal disease. RESULTS: The research includes the cases of 12 patients aged between 17 and 37 years old with an average age of 28.8 years old. The average gestation period was of 24.17 weeks, finding 50% of the patients within their third three-month period of pregnancy at the moment of diagnosis, 25% in their second three-month period and the remaining 25% in their first three-month period. The mean follow-up duration for this series was 84 months. 4 of them presented brain vascular lesions, 5 presented brain tumor lesions, 1 of them presented Chiari malformation, one lumbar disc herniation and 1 patient suffered from traumatic intracraneal hemorrhage. 8 of the 12 patients were subjected to neurosurgical procedures under general anesthetic, 2 for aneurysm embolizations and 2 for conservative treatments. Between the neurosurgical procedures 6 craniotomies were done, of wich 4 were to resection of the tumor and 2 for aneurysm clippings. There were done a transesfenoidal approach and a lumbar microdiscectomy. 2 of the 6 patients given craniotomies required external ventricular drainage before the operation. 5 elective cesareans were done in the group of patients given the craniotomies whilst of the rest the pregnancy was allowed to bring to term for reasons of pulmonary maturity. In our patients there were no cases of therapeutic abortion. There was found no morbidity no mortality neither in the mother nor in the fetus related to surgery. CONCLUSIONS: In our experience with pregnant patients who suffered from neurosurgical lesion and in the experience we got from the revision of the related literature, the surgery of intracranial lesions is well tolerated by the mothers and the fetus. It must though be considered, the possibility of labor through cesarean depending on the fetus' lung maturity.

[Aetiology of surgical infections in patients undergoing craniotomy]. / Etiología de las infecciones quirúrgicas en pacientes sometidos a craneotomía.

BACKGROUND: Postoperative infections in patients undergoing craniotomy constitute significant complications associated with increased hospital stay and patient morbidity and mortality. Knowing the aetiology of surgical infections after craniotomy may contribute to improving antibiotic prophylaxis and empirical treatment. METHOD: Information relating to surgical infections in patients undergoing craniotomy was obtained from a series of annual surveys on prevalence of infections in Spanish hospitals (EPINE) during the period 1999-2006. The study protocol collected relevant clinical information on patients with infection. Presence of infection was determined according to the Centres for Disease Control infection criteria. RESULTS: During the time period considered, 107 cases of surgical infections in patients undergoing craniotomy were diagnosed. Forty patients were women (37%) and 67 were male (63%). The mean age was 51.7 years (median 55, range 6-86 years). The duration of the intervention was over 180minutes in 49 patients (45.8%).Thirty-eight patients (35.5%) underwent emergency surgery. Seventy-eight patients (73%) received surgical prophylaxis. Thirty-eight patients (35.5%) had superficial infection of the surgical wound, 38 patients (35.5%) had deep wound infection (including bone flap) and 31 patients (29%), postoperative infections of organ or space (meningitis, subdural empyema or brain abscess). The most common aetiology corresponded to staphylococci (50%), mainly S. aureus (one third of them methicillin-resistant), Pseudomonas aeruginosa (11%), Enterobacter spp (10%) and Acinetobacter baumannii (9%). CONCLUSION: Empirical treatment of these infections should include a glycopeptide such as vancomycin and a beta-lactam with coverage against non-fermenting gram-negative bacilli.