Fully automatic mpMRI analysis using deep learning predicts peritumoral glioblastoma infiltration and subsequent recurrence.

Glioblastoma (GBM) is most aggressive and common adult brain tumor. The standard treatments typically include maximal surgical resection, followed adjuvant radiotherapy and chemotherapy. However, the efficacy of these treatment is often limited, as tumor often infiltrate into the surrounding brain tissue, often extending beyond the radiologically defined margins. This infiltration contributes to the high recurrence rate and poor prognosis associated with GBM patients, necessitating advanced methods for early and accurate detection of tumor infiltration. Despite the great promise traditional supervised machine learning shows in predicting tumor infiltration beyond resectable margins, these methods are heavily reliant on expert-drawn Regions of Interest (ROIs), which are used to construct multi-variate models of different Magnetic Resonance (MR) signal characteristics associated with tumor infiltration. This process is both time consuming and resource intensive. Addressing this limitation, our study proposes a novel integration of fully automatic methods for generating ROIs with deep learning algorithms to create predictive maps of tumor infiltration. This approach uses pre-operative multi-parametric MRI (mpMRI) scans, encompassing T1, T1Gd, T2, T2-FLAIR, and ADC sequences, to fully leverage the knowledge from previously drawn ROIs. Subsequently, a patch based Convolutional Neural Network (CNN) model is trained on these automatically generated ROIs to predict areas of potential tumor infiltration. The performance of this model was evaluated using a leave-one-out cross-validation approach. Generated predictive maps binarized for comparison against post-recurrence mpMRI scans. The model demonstrates robust predictive capability, evidenced by the average cross-validated accuracy of 0.87, specificity of 0.88, and sensitivity of 0.90. Notably, the odds ratio of 8.62 indicates that regions identified as high-risk on the predictive map were significantly more likely to exhibit tumor recurrence than low-risk regions. The proposed method demonstrates that a fully automatic mpMRI analysis using deep learning can successfully predict tumor infiltration in peritumoral region for GBM patients while bypassing the intensive requirement for expert-drawn ROIs.

Distinct gut microbiota signatures associated with progression of atherosclerosis in people living with HIV.

BACKGROUND: The relationship of microbiota composition dynamics and the progression of subclinical atherosclerosis in people with HIV (PWH) remains unknown. METHODS: 96-week, prospective, longitudinal study in virologically-suppressed PWH. Carotid intima-media thickness (cIMT) measurements and stool samples were obtained at baseline, 48-week and 96-week visits. cIMT progression was defined as an increase >10% and/or detection of new carotid plaque. To profile the gut microbiome, amplification and sequencing of 16S ribosomal-RNA (V3-V4 variable regions) were carried out following the Illumina protocol. Sequencing was performed with MiSeq platform. RESULTS: 191, 190 and 167 patients had available fecal samples for microbiome analysis at the baseline, 48- and 96-week visits, respectively. 87 (43%) participants showed atherosclerosis progression, and 54 (26.7%) presented new carotid plaque. No significant differences were observed in adjusted α-diversity indices between groups defined by cIMT progression. Beta-diversity determined through principal coordinate analysis distances showed that the groups exhibited distinct microbial profiles (PERMANOVA p-value = 0.03). Longitudinal analysis with ANCOM-BC2 adjusted for traditional cardiovascular risk factors, MSM and nadir CD4 count revealed that cIMT progression was consistently associated with Agathobacter and Ruminococcus_2, while non-progression was consistently associated with Prevotella_7. CONCLUSION: Progression of atherosclerosis in PWH might be associated with distinctive signatures in the gut microbiota.

Single-Stage Posterior Vomerine Ostectomy, Premaxillary Setback, Bilateral Gingivoperiosteoplasties and Primary Bilateral Cheiloplasty in Patients with Protuberant Premaxilla.

Various patients with complete bilateral cleft lip and palate present with a protruded premaxilla. Several techniques have been described for correctional repair of the projection with a plethora of unsatisfactory outcomes. This poses a challenge not only for the cleft team providing care but also for the patients and their respective families. Multiple patients suffer from residual deformities after inadequate primary repair, which increase surgical, financial, and psychological burden. Premaxillary setback with posterior vomerine ostectomy and complete bilateral cleft lip repair can promote alignment of the premaxilla with the maxillary prominences. To effectively address this challenging deformity, we describe a single-stage surgical technique that includes vomerine ostectomy posterior to the vomero-premaxillary suture, bilateral gingivoperiosteoplasties with complete bilateral cleft lip repair, and primary cleft rhinoplasty. Careful surgical planning is essential for adequate matching between the length of the protruded premaxilla and the extent of ostectomy. The described technique offers several advantages for the management of complete bilateral cleft lip with a projected premaxilla. It can be applied anywhere around the world and is most beneficial in underprivileged areas where patients suffer from restricted access to healthcare, absence of presurgical orthodontics and lack of sufficient resources.

Sex-specific Differences in IDH1-Wildtype Glioblastoma patients in the ReSPOND Consortium.

BACKGROUND: Understanding sex-based differences in glioblastoma patients is necessary for accurate personalized treatment planning to improve patient outcomes. PURPOSE: To investigate sex-specific differences in molecular, clinical and radiological tumor parameters, as well as survival outcomes in glioblastoma, isocitrate dehydrogenase-1 wildtype (IDH1-WT), grade 4 patients. METHODS: Retrospective data of 1832 glioblastoma, IDH1-WT patients with comprehensive information on tumor parameters was acquired from the Radiomics Signatures for Precision Oncology in Glioblastoma (ReSPOND) consortium. Data imputation was performed for missing values. Sex-based differences in tumor parameters, such as, age, molecular parameters, pre-operative KPS score, tumor volumes, epicenter and laterality were assessed through non-parametric tests. Spatial atlases were generated using pre-operative MRI maps to visualize tumor characteristics. Survival time analysis was performed through log-rank tests and Cox proportional hazard analyses. RESULTS: GBM was diagnosed at a median age of 64 years in females compared to 61.9 years in males (FDR = 0.003). Males had a higher Karnofsky Performance Score (above 80) as compared to females (60.4% females Vs 69.7% males, FDR = 0.044). Females had lower tumor volumes in enhancing (16.7 cm3 Vs. 20.6 cm3 in males, FDR = 0.001), necrotic core (6.18 cm3 Vs. 7.76 cm3 in males, FDR = 0.001) and edema regions (46.9 cm3 Vs. 59.2 cm3 in males, FDR = 0.0001). Right temporal region was the most common tumor epicenter in the overall population. Right as well as left temporal lobes were more frequently involved in males. There were no significant differences in survival outcomes and mortality ratios. Higher age, unmethylated O6-methylguanine-DNAmethyltransferase (MGMT) promoter and undergoing subtotal resection increased the mortality risk in both males and females. CONCLUSIONS: Our study demonstrates significant sex-based differences in clinical and radiological tumor parameters of glioblastoma, IDH1-WT, grade 4 patients. Sex is not an independent prognostic factor for survival outcomes and the tumor parameters influencing patient outcomes are identical for males and females. ABBREVIATIONS: IDH1-WT = isocitrate dehydrogenase-1 wildtype; MGMTp = O6-methylguanine-DNA-methyltransferase promoter; KPS = Karnofsky performance score; EOR = extent of resection; WHO = world health organization; FDR = false discovery rate.

Association of Variability and Hypertensive Loads in 24-h Blood Pressure With Mortality and Cardiovascular Risk.

BACKGROUND: Evidence shows that high 24-h blood pressure (BP) variability increases cardiovascular risk. We investigated whether 24-h BP variability relates to mortality and cardiovascular risk due to inherent variability and/or hypertensive loads in 24-h BP. METHODS: A total of 1,050 participants from the Maracaibo Aging Study (mean age, 66 years; women, 67.2%) underwent 24-h ambulatory BP monitoring and were followed between 2001 and 2016. To evaluate inherent BP variability, we used average real variability (ARV) as it captures variability among consecutive BP readings. 24-h systolic BP load was the proportion (%) of systolic BP readings ≥130 mm Hg during the daytime and ≥110 during the nighttime. Our primary endpoint was total mortality and major adverse cardiovascular endpoints (MACE). Statistics included Cox proportional models. RESULTS: During a median follow-up of 8.3 years, 299 participants died and 210 experienced MACE. Each +2 mm Hg (corresponding to 1-standard deviation) higher 24-h systolic ARV (mean value, 9.0 ±â€…2.0 mm Hg) was associated with higher hazard ratios (HRs) for mortality by 1.28-fold (95% confidence interval [CI], 1.14-1.43) and for MACE by 1.24-fold (95% CI, 1.08-1.42). Each 30% higher 24-h systolic BP load (median value, 63%) was associated with mortality and MACE with HRs of 1.29 (95% CI, 1.15-1.46) and 1.28 (95% CI, 1.10-1.48); respectively. After models were additionally adjusted by BP level, only ARV was associated with mortality (HR, 1.17; 95% CI, 1.04-1.33) and MACE (HR, 1.16; 95% CI, 1.00-1.34). CONCLUSIONS: High ARV and hypertensive loads in 24-h systolic BP were associated with mortality and cardiovascular risk, however, only ARV is associated independently of the BP level.

Manganese-Catalyzed Hydrogenation of Amides and Polyurethanes: Is Catalyst Inhibition an Additional Barrier to the Efficient Hydrogenation of Amides and Their Derivatives?

The hydrogenation of amides and other less electrophilic carbonyl derivatives with an N-C=O functionality requires significant improvements in scope and catalytic activity to be a genuinely useful reaction in industry. Here, we report the results of a study that examined whether such reactions are further disadvantaged by nitrogen-containing compounds such as aliphatic amines acting as inhibitors on the catalysts. In this case, an enantiomerically pure manganese catalyst previously established to be efficient in the hydrogenation of ketones, N-aryl-imines, and esters was used as a prototype of a manganese catalyst. This was accomplished by doping a model ester hydrogenation with various nitrogen-containing compounds and monitoring progress. Following from this, a protocol for the catalytic hydrogenation of amides and polyurethanes is described, including the catalytic hydrogenation of an axially chiral amide that resulted in low levels of kinetic resolution. The hypothesis of nitrogen-containing compounds acting as an inhibitor in the catalytic hydrogenation process has also been rationalized by using spectroscopy (high-pressure infrared (IR), nuclear magnetic resonance (NMR)) and mass spectrometry studies.

Cost benefit analysis of diversified farming systems across Europe: Incorporating non-market benefits of ecosystem services.

Crop diversification can enhance farm economic sustainability while reducing the negative impact on the environment and ecosystem services related. Despite the market and non-market benefits of crop diversification, monocropping is a widely used dominant practice in Europe. In this context, this works aims to assess the overall economic impact of several crop diversification systems across Europe and compared it to the monocropping system. For this purpose, an economic valuation by integrating market and non-market values for eight case studies distributed across three different European pedoclimatic regions (Southern Mediterranean, Northern Mediterranean and Boreal) is proposed. The economic valuation was conducted both in the short and medium-long term. For the short-term we conducted a social gross margin analysis, while for the medium-long term a cost-benefit analysis is developed. The results show an improvement in social gross margins for most of the diversification scenarios assessed when environmental and socio-cultural benefits are considered in the short-term. In the medium and long-term the transformation of cropping towards a more diversified agriculture is encouraged by greater economic benefits. These results provide a first insight in global economic performance of diversified cropping systems, whose main contribution relies on the integration of market and non-market values of ecosystem services from crop diversification. They are expected to be useful for guiding policy makers to promote crop diversification practices as a key instrument for building resilience in farming systems for an adaptive management to climate change.

Incidental Carcinoid Tumor of the Appendix After Appendectomy During Pregnancy.

Neuroendocrine tumors comprise a range of neoplasms with varying spectra of origin, biological activity, clinical features, and histological appearance. In this case report, we present a pregnant 33-year-old female who was brought to the emergency department (ED) complaining of acute right iliac fossa pain accompanied by diarrhea and vomiting. Initial management showed no improvement. Lab results, clinical history, and physical exam were suggestive of appendicitis, so an exploratory minimally invasive laparoscopic exam was performed. The histopathological analysis of the excised appendix confirmed the diagnosis of acute appendicitis and periappendicitis. Incidentally, a 0.6 cm neuroendocrine tumor (carcinoid tumor) was identified on the wall of the appendiceal tip. The tumor extended at multiple points into the subserosal fat, and the serous surface and the resection margin were negative for the tumor. After seven days of the initial procedure, the patient presented with abdominal pain and a fever. An abdominal ultrasound was performed, revealing the presence of free fluid. A second exploratory laparoscopy revealed adhesions between the fallopian tubes and cecum, as well as a collection of purulent fluid. The management consisted of adhesiolysis, cavity lavage, and drainage, along with antibiotic therapy, pain management, and close monitoring of the mother's and fetus's status. The patient had a successful recovery and was discharged home a week after surgery. She gave birth to a full-term, healthy baby and remains free of tumor relapse. This case highlights the importance of obtaining histopathological interpretation of any extracted tissue during surgery. Guidelines regarding the management of carcinoids during pregnancy are not available, and when considering surgical intervention, an open or laparoscopic approach must be carefully evaluated.

Facial nerve palsy following parotid gland surgery: A machine learning prediction outcome approach.

Introduction: Machine learning (ML)-based facial nerve injury (FNI) forecasting grounded on multicentric data has not been released up to now. Three distinct ML models, random forest (RF), K-nearest neighbor, and artificial neural network (ANN), for the prediction of FNI were evaluated in this mode. Methods: A retrospective, longitudinal, multicentric study was performed, including patients who went through parotid gland surgery for benign tumors at three different university hospitals. Results: Seven hundred and thirty-six patients were included. The most compelling aspects related to risk escalation of FNI were as follows: (1) location, in the mid-portion of the gland, near to or above the main trunk of the facial nerve and at the top part, over the frontal or the orbital branch of the facial nerve; (2) tumor volume in the anteroposterior axis; (3) the necessity to simultaneously dissect more than one level; and (4) the requirement of an extended resection compared to a lesser extended resection. By contrast, in accordance with the ML analysis, the size of the tumor (>3 cm), as well as gender and age did not result in a determining favor in relation to the risk of FNI. Discussion: The findings of this research conclude that ML models such as RF and ANN may serve evidence-based predictions from multicentric data regarding the risk of FNI. Conclusion: Along with the advent of ML technology, an improvement of the information regarding the potential risks of FNI associated with patients before each procedure may be achieved with the implementation of clinical, radiological, histological, and/or cytological data.

Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer's Disease.

Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer's disease (AD) being the most dominant, without efficacious drugs, and with only a few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I2 receptors (I2-IRs) that have been pointed out as relevant targets in AD. In this work, we explored structural modifications of well-established I2-IR ligands, giving access to derivatives with an imidazole-linked heterocycle as a common key feature. We report the synthesis, the affinity in human I2-IRs, the brain penetration capabilities, the in silico ADMET studies, and the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of this new bunch of I2-IR ligands. Selected compounds showed neuroprotective properties and beneficial effects in an in vitro model of Parkinson's disease, rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine, and showed crucial anti-inflammatory effects in a cellular model of neuroinflammation. After a preliminary pharmacokinetic study, we explored the action of our representative 2-(benzo[b]thiophen-2-yl)-1H-imidazole LSL33 in a mouse model of AD (5xFAD). Oral administration of LSL33 at 2 mg/Kg for 4 weeks ameliorated 5XFAD cognitive impairment and synaptic plasticity, as well as reduced neuroinflammation markers. In summary, this new I2-IR ligand that promoted beneficial effects in a well-established AD mouse model should be considered a promising therapeutic strategy for neurodegeneration.

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study.

BACKGROUND: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability. AIMS: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome. METHODS: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed. RESULTS: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality. CONCLUSIONS: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE.

Prevalence of risk factors associated with development of capsular contracture after placement of breast implants.

OBJECTIVE: To determinate the prevalence of the main risk factors associated with development of capsular contracture after placement of breast implants in a referral center. METHOD: Retrospect study on 210 patients where sociodemographic variables, Baker's clinical scale and histopathological results were recorded. RESULTS: Statistical analysis of 210 patients was performed; 98.1% were women. The average age was 47 years (± 11), body mass index 25 (± 10) and onset of symptoms 13 years (± 8.5). Sociodemographic factors: domestic work 63.3%. Alcoholism 70% and smoking 65.7%. The main reason for consultation was pain plus deformity in 81.6%. The risk factors with statistical significance were the history of trauma, with 83.3% (p = 0.004), and the subglandular plane, with 73.8% (p = 0.0115). Histopathology: fibrous capsule 81.4%. CONCLUSIONS: The prevalence of the risk factors described are similar to those reported in the literature. Only for the history of trauma and the subglandular plane there was statistical significance.

OBJETIVO: Determinar la prevalencia de los principales factores de riesgo asociados a contractura capsular posterior a mamoplastia de aumento en un centro de referencia. MÉTODO: Estudio retrospectivo de 210 pacientes en el que se registraron variables sociodemográficas, escala clínica de Baker y resultados histopatológicos. RESULTADOS: Se realizó el análisis estadístico de 210 pacientes; el 98.1% fueron mujeres. La edad promedio fue de 47 años (± 11), el índice de masa corporal 25 kg/m2 (± 10) y el inicio de los síntomas 13 años (± 8.5). Factores sociodemográficos: labores domésticas 63.3%. Alcoholismo 70% y tabaquismo 65.7%. El principal motivo de consulta fue dolor más deformidad, en el 81.6%. Los factores de riesgo con significancia estadística fueron el antecedente de traumatismo, con un 83.3% (p = 0.004), y el plano subglandular, con un 73.8% (p = 0.0115). Histopatología: cápsula fibrosa 81.4%. CONCLUSIONES: La prevalencia de los factores de riesgo descritos es similar a lo reportado en la literatura. Solo para el antecedente de traumatismo y el plano subglandular hubo significancia estadística.

Radiomic signatures of meningiomas using the Ki-67 proliferation index as a prognostic marker of clinical outcomes.

OBJECTIVE: The clinical behavior of meningiomas is not entirely captured by its designated WHO grade, therefore other factors must be elucidated that portend increased tumor aggressiveness and associated risk of recurrence. In this study, the authors identify multiparametric MRI radiomic signatures of meningiomas using Ki-67 as a prognostic marker of clinical outcomes independent of WHO grade. METHODS: A retrospective analysis was conducted of all resected meningiomas between 2012 and 2018. Preoperative MR images were used for high-throughput radiomic feature extraction and subsequently used to develop a machine learning algorithm to stratify meningiomas based on Ki-67 indices < 5% and ≥ 5%, independent of WHO grade. Progression-free survival (PFS) was assessed based on machine learning prediction of Ki-67 strata and compared with outcomes based on histopathological Ki-67. RESULTS: Three hundred forty-three meningiomas were included: 291 with WHO grade I, 43 with grade II, and 9 with grade III. The overall rate of recurrence was 19.8% (15.1% in grade I, 44.2% in grade II, and 77.8% in grade III) over a median follow-up of 28.5 months. Grade II and III tumors had higher Ki-67 indices than grade I tumors, albeit tumor and peritumoral edema volumes had considerable variation independent of meningioma WHO grade. Forty-six high-performing radiomic features (1 morphological, 7 intensity-based, and 38 textural) were identified and used to build a support vector machine model to stratify tumors based on a Ki-67 cutoff of 5%, with resultant areas under the curve of 0.83 (95% CI 0.78-0.89) and 0.84 (95% CI 0.75-0.94) achieved for the discovery (n = 257) and validation (n = 86) data sets, respectively. Comparison of histopathological Ki-67 versus machine learning-predicted Ki-67 showed excellent performance (overall accuracy > 80%), with classification of grade I meningiomas exhibiting the greatest accuracy. Prediction of Ki-67 by machine learning classifier revealed shorter PFS for meningiomas with Ki-67 indices ≥ 5% compared with tumors with Ki-67 < 5% (p < 0.0001, log-rank test), which corroborates divergent patient outcomes observed using histopathological Ki-67. CONCLUSIONS: The Ki-67 proliferation index may serve as a surrogate marker of increased meningioma aggressiveness independent of WHO grade. Machine learning using radiomic feature analysis may be used for the preoperative prediction of meningioma Ki-67, which provides enhanced analytical insights to help improve diagnostic classification and guide patient-specific treatment strategies.

Antifungal and Insecticidal Activities of Selected Plant Species from Cloud Forest of Veracruz, Mexico: A Contribution to the Search of Novel Control Agents against Ambrosia Pest Complexes.

The antifungal and insecticidal activities of 34 extracts from 27 plant species were evaluated against fungal phytopathogens of the genus Fusarium and Xyleborus Scolytine ambrosia beetles involved in Fusarium dieback (FD) and laurel wilt (LW) diseases. Sixteen extracts caused mycelial growth inhibition (MGI) above 23 % at 2 mg mL-1 against F. solani, those from S. nudum and M. argyrophylla exhibited the highest MGI (57 % and 49 %, respectively). Thirteen extracts displayed significant antifungal activity against F. kuroshium, those from C. nocturnum and M. argyrophylla exhibited the highest MGI (100 % and 54.9 %, respectively). Additionally, ten plants extracts caused mortality in at least one of the beetle species tested, mainly from Solanaceae species. In the most active species, 39 phenolics were identified that may have contributed to their biological effects. This study is one of the first to report the potential of plant-derived natural products against the causative agents of FD and LW.

The role of corticosteroids in patients hospitalized for COVID-19 at Mexico general Hospital.

OBJECTIVE: To compare the evolution of hospitalized patients infected with SARS-CoV-2 who received corticosteroid-based treatment versus patients who received standard therapy. METHOD: Retrospective, observational, and analytical study. Clinical records were collected from the different intensive care units, and data were obtained from confirmed COVID-19 patients over 18 years of age who were hospitalized. The population was divided into two groups: patients who received corticosteroid treatment, and those who received standard therapy. RESULTS: A total of 1603 patients were admitted to hospital, and of these 984 (62.9%) were discharged due to death. The main result was the identification by odds ratio (OR: 4.68; 95% confidence interval [95% CI]: 3.75-5.83; p = 0.001) as risk for death to the use of systemic steroids, as well as the use of invasive mechanical ventilation (OR: 2.26; 95% CI: 1.80-2.82; p < 0.001). The male gender was the most affected with 1051 (65.6%) patients. Mean age was 56 years (± 14). CONCLUSIONS: Corticosteroid use was associated with poor prognosis in patients hospitalized for COVID-19 compared to those receiving standard therapy.

OBJETIVO: Comparar la evolución de los pacientes hospitalizados infectados por SARS-CoV-2 que recibieron tratamiento a base de corticoesteroides frente a los pacientes que recibieron la terapia estándar. MÉTODO: Estudio de tipo retrospectivo, observacional y analítico. Se recolectaron los expedientes clínicos de las diferentes unidades de terapia intensiva y se obtuvieron datos de los pacientes confirmados de COVID-19, mayores de 18 años, que estuvieron hospitalizados. Se dividió la población en dos grupos: pacientes que recibieron tratamiento con corticoesteroides y pacientes que recibieron terapia estándar. RESULTADOS: De un total de 1603 pacientes ingresados a hospitalización, 984 (62.9%) fallecieron. El resultado principal fue la identificación mediante razón de momios (odds ratio [OR]: 4.68; intervalo de confianza del 95% [IC95%]: 3.75-5.83; p = 0.001) como riesgo para defunción con uso de esteroides sistémicos, así como con uso de ventilación mecánica invasiva (OR: 2.26; IC95%: 1.80-2.82; p < 0.001). El sexo masculino fue el más afectado, con 1051 (65.6%) pacientes. La media de edad fue de 56 años (± 14). CONCLUSIONES: El uso de corticoesteroides se asoció con mal pronóstico en los pacientes hospitalizados por COVID-19, en comparación con los que recibieron la terapia estándar.

Correlation of liver fibrosis quantification by morphometry using HepaScan with the analysis of liver biopsies. A pilot study.

BACKGROUND: The gold standard for determining the degree of liver fibrosis (LF) continues to be biopsy evaluation. There are morphometry techniques that allow LF to be quantified on histopathological studies. OBJECTIVE: To measure the correlation between LF histological evaluation and fibrosis percentage (FP) morphometric quantification using the HepaScan software. MATERIAL AND METHODS: Observational, analytical, cross-sectional, prospective, prolective pilot study in which liver histological sections from 29 people who died from some liver disease and from 22 people who died from other causes (controls) were analyzed. FP was calculated with HepaScan on digital photographs of histological sections stained with the Masson technique, comparing it with the diagnosis established by three expert pathologists. RESULTS: Four-hundred and one images from the group with liver disease and 250 from the control group were analyzed. Inter-observer agreement had a kappa index of 0.329. There were FP statistically significant differences (p = 0.0001) between histopathological classification groups. HepaScan predictive capacity based on the area under the receiver operating characteristic curve was 0.983, 0.812, and 0.895 for mild, moderate, and severe fibrosis, respectively. CONCLUSIONS: HepaScan showed very good performance for evaluating FP in histological sections, which is why it can contribute to qualitative pathological diagnosis.

ANTECEDENTES: El estándar de oro para determinar el grado de fibrosis hepática (FH) continúa siendo la evaluación de la biopsia. Existen técnicas de morfometría que permiten cuantificar la FH en estudios histopatológicos. OBJETIVO: Medir la correlación entre la evaluación histológica de FH y la cuantificación por morfometría del porcentaje de fibrosis (PF) mediante HepaScan. MATERIAL Y MÉTODOS: Estudio piloto observacional, analítico, transversal, prospectivo y prolectivo en el que se analizaron cortes histopatológicos de hígado de 29 personas fallecidas por alguna hepatopatía y 22 personas fallecidas por otras causas (controles). El PF se calculó con HepaScan en fotografías digitales de cortes histológicos teñidos con la técnica Masson, comparándolo con el diagnóstico de tres patólogos expertos. RESULTADOS: Fueron analizadas 401 imágenes del grupo con hepatopatía y 250 del grupo de control. La concordancia interobservador tuvo un índice kappa de 0.329. Entre los grupos de clasificación histopatológica existieron diferencias estadísticas en el PF (p = 0.0001). La capacidad predictiva de HepaScan con base en el área bajo la curva característica operativa del receptor fue de 0.983, 0.812 y 0.895 para fibrosis leve, moderada y severa, respectivamente. CONCLUSIONES: HepaScan mostró muy buen desempeño para evaluar el PF en cortes histológicos, por lo que puede coadyuvar al diagnóstico patológico cualitativo.

Correlación de la cuantificación de fibrosis hepática por morfometría mediante HepaScan con el análisis de las biopsias hepáticas. Estudio piloto / Correlation of liver fibrosis quantification by morphometry using HepaScan with the analysis of liver biopsies. A pilot study

Resumen Antecedentes: El estándar de oro para determinar el grado de fibrosis hepática (FH) continúa siendo la evaluación de la biopsia. Existen técnicas de morfometría que permiten cuantificar la FH en estudios histopatológicos. Objetivo: Medir la correlación entre la evaluación histológica de FH y la cuantificación por morfometría del porcentaje de fibrosis (PF) mediante HepaScan. Material y métodos: Estudio piloto observacional, analítico, transversal, prospectivo y prolectivo en el que se analizaron cortes histopatológicos de hígado de 29 personas fallecidas por alguna hepatopatía y 22 personas fallecidas por otras causas (controles). El PF se calculó con HepaScan en fotografías digitales de cortes histológicos teñidos con la técnica Masson, comparándolo con el diagnóstico de tres patólogos expertos. Resultados: Fueron analizadas 401 imágenes del grupo con hepatopatía y 250 del grupo de control. La concordancia interobservador tuvo un índice kappa de 0.329. Entre los grupos de clasificación histopatológica existieron diferencias estadísticas en el PF (p = 0.0001). La capacidad predictiva de HepaScan con base en el área bajo la curva característica operativa del receptor fue de 0.983, 0.812 y 0.895 para fibrosis leve, moderada y severa, respectivamente. Conclusiones: HepaScan mostró muy buen desempeño para evaluar el PF en cortes histológicos, por lo que puede coadyuvar al diagnóstico patológico cualitativo.

Abstract Background: The gold standard for determining the degree of liver fibrosis (LF) continues to be biopsy evaluation. There are morphometry techniques that allow LF to be quantified on histopathological studies. Objective: To measure the correlation between LF histological evaluation and fibrosis percentage (FP) morphometric quantification using the HepaScan software. Material and methods: Observational, analytical, cross-sectional, prospective, prolective pilot study in which liver histological sections from 29 people who died from some liver disease and from 22 people who died from other causes (controls) were analyzed. FP was calculated with HepaScan on digital photographs of histological sections stained with the Masson technique, comparing it with the diagnosis established by three expert pathologists. Results: Four-hundred and one images from the group with liver disease and 250 from the control group were analyzed. Inter-observer agreement had a kappa index of 0.329. There were FP statistically significant differences (p = 0.0001) between histopathological classification groups. HepaScan predictive capacity based on the area under the receiver operating characteristic curve was 0.983, 0.812, and 0.895 for mild, moderate, and severe fibrosis, respectively. Conclusions: HepaScan showed very good performance for evaluating FP in histological sections, which is why it can contribute to qualitative pathological diagnosis.

Changes in Liver Lipidomic Profile in G2019S-LRRK2 Mouse Model of Parkinson's Disease.

The identification of Parkinson's disease (PD) biomarkers has become a main goal for the diagnosis of this neurodegenerative disorder. PD has not only been intrinsically related to neurological problems, but also to a series of alterations in peripheral metabolism. The purpose of this study was to identify metabolic changes in the liver in mouse models of PD with the scope of finding new peripheral biomarkers for PD diagnosis. To achieve this goal, we used mass spectrometry technology to determine the complete metabolomic profile of liver and striatal tissue samples from WT mice, 6-hydroxydopamine-treated mice (idiopathic model) and mice affected by the G2019S-LRRK2 mutation in LRRK2/PARK8 gene (genetic model). This analysis revealed that the metabolism of carbohydrates, nucleotides and nucleosides was similarly altered in the liver from the two PD mouse models. However, long-chain fatty acids, phosphatidylcholine and other related lipid metabolites were only altered in hepatocytes from G2019S-LRRK2 mice. In summary, these results reveal specific differences, mainly in lipid metabolism, between idiopathic and genetic PD models in peripheral tissues and open up new possibilities to better understand the etiology of this neurological disorder.

Subclinical atherosclerosis burden in non-diabetic hypertensives treated in primary care center: the IMTABI study.

BACKGROUND: Identifying patients at high risk of cardiovascular disease in primary prevention is a challenging task. This study aimed at detecting subclinical atherosclerosis burden in non-diabetic hypertensive patients in a primary care centre. METHODS: Clinical, anthropometric and analytical data were collected from patients with hypertension who were free from clinical vascular disease and diabetes. The cardiovascular risk was assessed using the SCORE system. Subclinical atherosclerosis burden was assessed by carotid ultrasonography (intima-medial thickness [IMT] and plaque) and measurement of the ankle-brachial index (ABI). RESULTS: Out of 140 patients, 59 (42%) have carotid plaque, 32 (23%) have IMT higher than 75% and 12 (9%) have an ABI < 0.9. Total atherosclerosis burden was present in 91 (65%) of the subjects. Consequently, 59 (42%) patients were re-classified into the very high-risk category. In multivariate analyses, smoking, creatinine levels and duration of hypertension were associated with atherosclerosis burden. In contrast, only smoking and age were associated with the presence of carotid plaque. Almost 90% of patients were treated with hypotensive drugs, half of them combined several drugs and 60% were well-controlled. Only 30% received statins in monotherapy and only less than 20% had an LDL cholesterol < 100 mg/dL. CONCLUSIONS: In non-diabetic hypertensive patients managed at a primary care centre, 4 out of 10 had subclinical atherosclerosis burden and were re-classified into the very high- risk category. There was clear undertreatment with lipid-lowering drugs of most LDL cholesterol inappropriate levels, according to current clinical guidelines.

Microstructure, Phase Evolution, and Chemical Behavior of CrCuFeNiTiAlx High Entropy Alloys Processed by Mechanical Alloying.

High entropy alloys (HEAs) of the type CrCuFeNiTi-Alx were processed through mechanical alloying. The aluminum concentration was varied in the alloy, to determine its effect on the HEAs' microstructure, phase formation, and chemical behavior. X-ray diffraction studies performed on the pressureless sintered samples revealed the presence of structures composed of face centered cubic (FCC) and body centered cubic (BCC) solid-solution phases. Since the valences of the elements that form the alloy are different, a nearly stoichiometric compound was obtained, increasing the final entropy of the alloy. The aluminum was partly responsible for this situation, which also favored transforming part of the FCC phase into BCC phase on the sintered bodies. X-ray diffraction also indicated the formation of different compounds with the alloy's metals. Bulk samples exhibited microstructures with different phases. The presence of these phases and the results of the chemical analyses revealed the formation of alloying elements that, in turn, formed a solid solution and, consequently, had a high entropy. From the corrosion tests, it could be concluded that the samples with a lower aluminum content were the most resistant to corrosion.