Focal-to-bilateral tonic-clonic seizures and High-grade CMV-infection are poor survival predictors in Tumor-related Epilepsy Adult-type diffuse gliomas-A single-center study and literature review.

Introduction: Previous studies have reported a correlation between a high-grade CMV-infection and an unfavorable prognosis in glioblastoma (GB). Coversely, epilepsy has been associated with a more favorable outcome in GB patients. Despites epilepsy and CMV share similar molecular mechanisms in GB tumoral microenvironment, the correlation between Tumor-Related-Epilepsy (TRE) and CMVinfection remains unexplored. The aim of our study is to examine the correlation between the dregree of CMV infection and seizure types on the survival of TRE Adult-type-diffuse-glioma. To achieve this objective, we conducted a comprehensive literature review to assess our results regarding previous publications. Methods: We conducted a retrospective-observational study on TRE Adult-type-diffuse-gliomas treated at a single center in Mexico from 2010 to 2018. Tumor tissue and cDNA were analyzed by immunochemistry (IHC) for CMV (IE and LA antigens) at the Karolinska Institute in Sweden, and RT-PCR for CMV-gB in Torreon Mexico, respectively. Bivariate analysis (X2-test) was performed to evaluate the association between subtypes of Adult-type-diffuse-glioma (IDH-mut grade 4 astrocytoma vs. IDH-wt glioblastoma) and the following variables: type of hemispheric involvement (mesial vs. neocortical involvement), degree of CMV infection (<25%vs. >25% infected-tumoral cells) and seizure types [Focal awareness, focal impaired awareness, and FBTCS]. Kaplan Meier and Cox analyses were performed to determine the risk, p < 0.05 was considered statistically significant. Results: Sixty patients with TRE Adult type diffuse gliomas were included (80% IDH-wt glioblastoma and 20% IDH-mut grade 4astrocytomas). The mean age was 61.5 SD ± 18.4, and 57% were male. Fifty percent of the patients presented with mesial involvement of the hemysphere. Seizure types included focal awareness (15%), focal impaired awareness (43.3%), and FBTCS (41.7%). Ninety percent of cases were treated with Levetiracetam and 33.3% presented Engel-IA postoperative seizure control. More than 90% of samples were positive for CMV-immunohistochemistry (IHC). However, all cDNA analyzed by RT-PCR return negative results. The median of overall survival (OS) was 15 months. High-grade CMV-IE infection (14 vs. 25 months, p<0.001), mesial involvement (12 vs. 18 months, p<0.001), and FBTCS were associated with worse OS (9 vs.18 months for non-FBTCS). Multivariate analysis demonstrated that high-grade CMV infection (HR = 3.689, p=0.002) and FBTCS (HR=7.007, p<0.001) were independent unfavorable survival factors. Conclusions: CMV induces a proinflammatory tumoral microenvironment that contributes to the developmet of epilepsy. Tumor progression could be associated not only with a higher degree of CMV infection but also to epileptogenesis, resulting in a seizure phenotype chracterized by FBTCS and poor survival outcomes. This study represents the first survival analysis in Latin America to include a representative sample of TRE Adult-type diffuse gliomas considering CMV-infection-degree and distinguishing features (such as FBTCS) that might have potential clinical relevance in this group of patients. Further prospective studies are required to validate these results.

Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): final results of a randomised phase 3 study.

BACKGROUND: The aim of the COSMIC-312 trial was to evaluate cabozantinib plus atezolizumab versus sorafenib in patients with previously untreated advanced hepatocellular carcinoma. In the initial analysis, cabozantinib plus atezolizumab significantly prolonged progression-free survival versus sorafenib. Here, we report the pre-planned final overall survival analysis and updated safety and efficacy results following longer follow-up. METHODS: COSMIC-312 was an open-label, randomised, phase 3 study done across 178 centres in 32 countries. Patients aged 18 years or older with previously untreated advanced hepatocellular carcinoma were eligible. Patients must have had measurable disease per Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1), and adequate marrow and organ function, including Child-Pugh class A liver function; those with fibrolamellar carcinoma, sarcomatoid hepatocellular carcinoma, or combined hepatocellular cholangiocarcinoma were ineligible. Patients were randomly assigned (2:1:1) using a web-based interactive response system to a combination of oral cabozantinib 40 mg once daily plus intravenous atezolizumab 1200 mg every 3 weeks, oral sorafenib 400 mg twice daily, or oral single-agent cabozantinib 60 mg once daily. Randomisation was stratified by disease aetiology, geographical region, and presence of extrahepatic disease or macrovascular invasion. Dual primary endpoints were for cabozantinib plus atezolizumab versus sorafenib: progression-free survival per RECIST 1.1, as assessed by a blinded independent radiology committee, in the first 372 randomly assigned patients (previously reported) and overall survival in all patients randomly assigned to cabozantinib plus atezolizumab or sorafenib. The secondary endpoint was progression-free survival in all patients randomly assigned to cabozantinib versus sorafenib. Outcomes in all randomly assigned patients, including final overall survival, are presented. Safety was assessed in all randomly assigned patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT03755791. FINDINGS: Between Dec 7, 2018, and Aug 27, 2020, 432 patients were randomly assigned to combination treatment, 217 to sorafenib, and 188 to single-agent cabozantinib, and included in all efficacy analyses. 704 (84%) patients were male and 133 (16%) were female. 824 of these patients received at least one dose of study treatment and were included in the safety population. Median follow-up was 22·1 months (IQR 19·3-24·8). Median overall survival was 16·5 months (96% CI 14·5-18·7) for the combination treatment group and 15·5 months (12·2-20·0) for the sorafenib group (hazard ratio [HR] 0·98 [0·78-1·24]; stratified log-rank p=0·87). Median progression-free survival was 6·9 months (99% CI 5·7-8·2) for the combination treatment group, 4·3 months (2·9-6·1) for the sorafenib group, and 5·8 months (99% CI 5·4-8·2) for the single-agent cabozantinib group (HR 0·74 [0·56-0·97] for combination treatment vs sorafenib; HR 0·78 [99% CI 0·56-1·09], p=0·05, for single-agent cabozantinib vs sorafenib). Grade 3 or 4 adverse events occurred in 281 (66%) of 429 patients in the combination treatment group, 100 (48%) of 207 patients in the sorafenib group, and 108 (57%) of 188 patients in the single-agent cabozantinib group; the most common were hypertension (37 [9%] vs 17 [8%] vs 23 [12%]), palmar-plantar erythrodysaesthesia (36 [8%] vs 18 [9%] vs 16 [9%]), aspartate aminotransferase increased (42 [10%] vs eight [4%] vs 17 [9%]), and alanine aminotransferase increased (40 [9%] vs six [3%] vs 13 [7%]). Serious adverse events occurred in 223 (52%) patients in the combination treatment group, 84 (41%) patients in the sorafenib group, and 87 (46%) patients in the single agent cabozantinib group. Treatment-related deaths occurred in six (1%) patients in the combination treatment group (encephalopathy, hepatic failure, drug-induced liver injury, oesophageal varices haemorrhage, multiple organ dysfunction syndrome, and tumour lysis syndrome), one (<1%) in the sorafenib group (general physical health deterioration), and four (2%) in the single-agent cabozantinib group (asthenia, gastrointestinal haemorrhage, sepsis, and gastric perforation). INTERPRETATION: First-line cabozantinib plus atezolizumab did not improve overall survival versus sorafenib in patients with advanced hepatocellular carcinoma. The progression-free survival benefit of the combination versus sorafenib was maintained, with no new safety signals. FUNDING: Exelixis and Ipsen.

Neurococcidiomycosis in children with hydrocephalus: assessment of functional outcome, quality of life and survival in relation to neuroimaging findings.

PURPOSE: Coccidioidal meningitis (CM) is an uncommon disease frequently misdiagnosed. Neuroimaging and mortality are not considered in detail in previous pediatric CM series. Our objective is to evaluate outcome of pediatric neurococcidiomycosis in relation to neuroimaging findings. METHODS: We performed a prospective, observational, cross-sectional study in children with hydrocephalus and CM treated at Specialties Hospital in Torreon, Mexico (between 2015 and 2020). The outcome was evaluated by Hydrocephalus Outcome Questionnaire (HOQ) and the modified Rankin Scale (mRS). Follow-up was established at the first shunt surgery and survival since CM diagnosis confirmation. Neuroimaging was analyzed in relation to clinical data, outcome and survival. Kaplan-Meier analysis was performed with IBM-SPSS-25. RESULTS: Ten pediatric cases with CM and hydrocephalus were reported. Aged 6-228 months, 60% were female. Mean number of surgeries was 4.3 SD ± 3 (range 1-15). Asymmetric hydrocephalus was the most common neuroimaging finding (70%), followed by cerebral vasculitis (20%) and isolated fourth ventricle (IFV) (20%). The mean HOQ overall score was 0.338 SD ± 0.35. A minimum follow-up of 18 months was reported. Mean survival was 13.9 SD ± 6.15 months (range 3-24). Poor survival was correlated with asymmetric hydrocephalus (p = 0.335), cerebral vasculitis (p = 0.176), IFV (p < 0.001), bacterial superinfection (p = 0.017), lower mRS scores at hospital discharge (p = 0.017) and during follow-up (p = 0.004). The mortality rate was 20%. CONCLUSIONS: We report the largest series in Latin America of pediatric CM and hydrocephalus. Asymmetric hydrocephalus, IFV and cerebral vasculitis are complications that increase mortality and must be early diagnosed for a timely surgical and medical treatment. HOQ and mRS could be alternative scales to evaluate outcome in these patients. After a long follow-up (18 months), survival remained poor after diagnosis confirmation in our series.

Transformation of a long-standing phosphaturic tumor-inducing osteomalacia into malignancy.

Key Clinical Message: Tumor-induced osteomalacia is a paraneoplastic syndrome characterized by renal phosphate wasting and deranged bone turnover. Clinicians should consider tumor-induced osteomalacia in unexplained hypophosphatemia and investigate for underlying tumors. Abstract: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, which leads to deranged bone turnover. TIO is usually associated with benign mesenchymal tumors, although it has also been reported in malignant tumors. We present the case of a 56-year-old individual who experienced a protracted 6-year clinical course characterized by hypophosphatemia, weakness, and kyphosis, alongside the presence of a foot tumor. Subsequently, this lesion displayed malignant behavior and was ultimately diagnosed as a high-grade sarcoma. To date, this case is among the 10 reported cases in the literature of a mesenchymal tumor associated with TIO undergoing malignant transformation. This report underscores the importance of a comprehensive evaluation of patients with unexplained hypophosphatemia and highlights the need for diligent follow-up to detect possible malignant transformation of the underlying tumor. Clinicians should consider TIO in the differential diagnosis of hypophosphatemia and promptly investigate for the presence of an underlying tumor, as early detection may improve the patient's prognosis.

Efficacy and safety of the proposed bevacizumab biosimilar BAT1706 compared with reference bevacizumab in patients with advanced nonsquamous non-small cell lung cancer: A randomized, double-blind, phase III study.

BACKGROUND: BAT1706 is a proposed biosimilar of bevacizumab (Avastin®). We aimed to compare the efficacy and safety of BAT1706 with that of EU-sourced reference bevacizumab (EU-bevacizumab) in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). METHODS: Patients were randomized 1:1 to BAT1706 plus paclitaxel and carboplatin (BAT1706 arm) or EU-bevacizumab plus paclitaxel and carboplatin (EU-bevacizumab arm) given every 3 weeks for six cycles, followed by maintenance therapy with BAT1706 or EU-bevacizumab. The primary endpoint was overall response rate at week 18 (ORR18 ). Clinical equivalence was demonstrated if the 90% confidence interval (CI) of the BAT1706:EU-bevacizumab ORR18 risk ratio was contained within the predefined equivalence margins of 0.75-1.33 (China National Medical Products Administration requirements), or 0.73-1.36 (US Food and Drug Administration), or if the 95% CI of the ORR18 risk difference between treatments was contained within the predefined equivalence margin of -0.12 to 0.15 (EMA requirements). RESULTS: In total, 649 randomized patients (BAT1706, n = 325; EU-bevacizumab, n = 324) received at least one cycle of combination treatment. The ORR18 was comparable between the BAT1706 and EU-bevacizumab arms (48.0% and 44.5%, respectively). The ORR18 risk ratio of 1.08 (90% CI: 0.94-1.24) and the ORR18 risk difference of 0.03 (95% CI: -0.04 to 0.11) were within the predefined equivalence margins, demonstrating the biosimilarity of BAT1706 and EU-bevacizumab. The safety profile of BAT1706 was consistent with that of EU-bevacizumab and no new safety signals were observed. CONCLUSION: In patients with advanced nonsquamous NSCLC, BAT1706 demonstrated clinical equivalence to EU-bevacizumab in terms of efficacy, safety, pharmacokinetics, and immunogenicity.

A novel mutation c.457C > T p.Q153 in the HMBS gene in a Mexican woman with acute intermittent porphyria.

Key Clinical Message: The detection of a novel HMBS gene mutation (c.457C > T) in a Mexican woman with acute intermittent porphyria underscores the importance of expanding genetic analyses in diverse populations to improve diagnosis, management, and knowledge of the disease's clinical implications. Abstract: Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a deficiency in the enzymatic activity of porphobilinogen deaminase (HMBS), resulting in the accumulation of toxic heme metabolites. In this report, we present the case of a Mexican woman with AIP who experienced recurrent episodes of severe abdominal pain, weakness, vomiting, and insomnia. Despite the challenges in diagnosis and treatment, genetic analysis revealed a novel HMBS mutation, c.457C > T (p.Q153X), located in exon 9. This mutation induces a premature translational stop codon and had not been previously reported in medical literature among individuals with AIP. Remarkably, the patient exhibited a positive response to RNA interference therapy. We hypothesize that this novel HMBS mutation may potentially account for the more severe clinical presentation observed in this case. However, further research is necessary to establish a definitive link between this specific mutation and disease severity. The prevalence and genetic variants of AIP in Mexico remain largely unknown, underscoring the importance of conducting additional research and expanding genetic analyses to gain a better understanding of the clinical implications associated with these mutations.

Analysis of the Mechanical Properties of a Stabilized Subgrade Type Soil under a Sustainable Approach for Construction.

This article presents an experimental study to analyze the mechanical properties of a soil stabilized with ordinary Portland cement (OPC) under a sustainable approach consisting of a significant substitution of OPC for sugarcane bagasse ash (SCBA) to reduce the quantity of cement used in the stabilization, reaching the necessary mechanical requirements for its use as a subgrade layer. Soil specimens were elaborated with 3%, 5%, and 7% OPC as a stabilizing agent by weight of the soil. These mixtures were then partially substituted with 25%, 50%, and 75% SCBA, with these percentages being by weight of the stabilizer (OPC). Compaction, compressive strength, and California bearing ratio (CBR) tests were performed to evaluate the mechanical properties of the specimens. The results indicate that a 25% substitution of OPC by SCBA shows a similar performance to the mixture with only Portland cement, so a reduction in OPC use can be made. Further, with a substitution of 100% OPC by SCBA, the CBR of natural soil without stabilizers is improved.

Bone bending strength and BMD of female athletes in volleyball, soccer, and long-distance running.

PURPOSE: The purpose of the study was to determine whether sports training comprised of (1) high-impact loading sport in volleyball (VOL), (2) odd impact loading sport in soccer (SOC), and (3) low impact sport in distance running (RUN) were associated with tibial bending strength and calcaneus bone mineral density (BMD), and ulnar bending strength and wrist BMD. METHOD: Female athletes comprised of 13 VOL, 22 SOC, and 22 RUN participated in the study. Twenty-three female non-athletes (NA) served as the comparison group. Tibial and ulnar bending strength (EI, Nm2) were assessed using a mechanical response tissue analyzer (MRTA). Calcaneus and wrist BMD were assessed using a peripheral X-ray absorptiometry. Group means differences among the study groups were determined using ANCOVA with age, weight, height, percent body fat, ethnicity/race, and training history serving as covariates. RESULTS: Tibial EI of VOL (228.3 ± 138 Nm2) and SOC (208.6 ± 115 Nm2) were greater (p < 0.05) compared to NA (101.2 ± 42 Nm2). Ulnar EI of SOC (54.9 ± 51 Nm2) was higher (p < 0.05) than NA (27.2 ± 9 Nm2). Calcaneus BMD of VOL (0.618 ± 0.12 g/cm2), SOC (0.621 ± 0.009 g/cm2), and RUN (0.572 ± 0.007 g/cm2) were higher (p < 0.05) than NA (0.501 ± 0.08 g/cm2), but not different between athletic groups. Wrist BMD of VOL (0.484 ± .06 g/cm2) and SOC (0.480 ± 0.06 g/cm2) were higher (p < 0.05) than NA (0.443 ± 0.04 g/cm2). CONCLUSIONS: Female VOL athletes exhibit greater tibial bending strength than RUN and NA, but not greater than SOC. Female SOC athletes exhibit greater ulnar bending strength and wrist BMD than NA.

Portland Cement-Based Grouts Enhanced with Basalt Fibers for Post-Tensioned Concrete Duct Filling.

In post-tensioned systems, grouts act as a last line of defense to prevent the penetration of harmful compounds such as chlorides, moisture and other substances that cause corrosion in the prestressing steel. For this reason, improving grouts results in the enhancement of the overall durability of the structure. In this study, the physical properties of grouts with basalt microfiber additions in the amounts of 0.03, 0.07 and 0.10% with respect to the mix volume were evaluated. The fresh properties included flowability and unit mass. Specimens were fabricated to evaluate drying shrinkage, compressive strength, air permeability and rapid permeability to chloride ions. The incorporation of basalt microfibers showed a beneficial effect on the physical properties of the grout by increasing the drying shrinkage resistance and decreasing the permeability compared to the reference mix and two commercial dry prepackaged grouts. The optimal grout mix was the one with a percentage of basalt microfibers of 0.10%, which decreased drying shrinkage by 15.98% at 14 days compared to the reference mix, and permeability to chloride ions decreased by 10.82% compared to the control mix.

Multivariate optimization of dispersive liquid-liquid microextraction using ionic liquid for the analysis of ultraviolet filters in natural waters.

In this work, a vortex-assisted dispersive liquid-liquid microextraction method, using an ionic liquid as the extracting solvent was developed, for the simultaneous analysis of three UV filters in different water samples. The extracting and dispersive solvents were selected in a univariate way. Then, the parameters such as the volume of the extracting and dispersive solvents, pH and ionic strength were evaluated using a full experimental design 24, followed by Doehlert matrix. The optimized method consisted of 50 µL of extracting solvent (1-octyl-3-methylimidazolium hexafluorophosphate), 700 µL of dispersive solvent (acetonitrile) and pH of 4.5. When combined with high-performance liquid chromatography, the method limit of detection ranged from 0.3 to 0.6 µg L-1, enrichment factors between 81 and 101%, and the relative standard deviation between 5.8 and 10.0%. The developed method demonstrated effectiveness in concentrating UV filters in both river and seawater samples, being a simple and efficient option for this type of analysis.

The Inflammatory Biomarkers Behavior Profile of Patients Following Elective Degenerative Spine Surgery and Differences Compared to Those Coursing With a Postoperative Spinal Infection: Protocol for a Systematic Review.

BACKGROUND: The incidence of postoperative spinal infection (PSI) ranges from 0% to 10%, with devastating effects on the patient prognosis because of higher morbidity while increasing costs to the health care system. PSIs are elusive and difficult to diagnose, especially in the early postoperative state, because of confusing clinical symptoms, rise in serum biomarkers, or imaging studies. Current research on diagnosis has focused on serum biomarkers; nevertheless, most series rely on retrospective cohorts where biomarkers are studied individually and at different time points. OBJECTIVE: This paper presents the protocol for a systematic review that aims to determine the inflammatory biomarker behavior profile of patients following elective degenerative spine surgery and their differences compared to those coursing with PSIs. METHODS: The proposed systematic review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. This protocol was registered at PROSPERO on January 19, 2022. We will include studies related to biomarkers in adult patients operated on for degenerative spinal diseases and those developing PSIs. The following information will be extracted from the papers: (1) study title; (2) study author; (3) year; (4) evidence level; (5) research type; (6) diagnosis group (elective postoperative degenerative disease or PSI); (7a) region (cervical, thoracic, lumbosacral, and coccygeal); (7b) type of infection by anatomical or radiological site; (8) surgery type (including instrumentation or not); (9) number of cases; (10) mean age or individual age; (11) individual serum biomarker values from the preoperative state up to 90 days postoperative for both groups, including (10a) interleukin-6, (10b) presepsin, (10c) erythrocyte sedimentation rate, (10d) leukocyte count, (10e) neutrophil count, (10f) C-reactive protein, (10g) serum amyloid, (10h) white cell count, (10i) albumin, (10j) prealbumin, (10k) procalcitonin, (10l) retinol-associated protein, and (10m) Dickkopf-1; (11) postoperative days at symptoms or diagnosis; (12) type of organism; (13) day of starting antibiotics; (14) duration of treatment; and (15) any biases (including comorbidities, especially those affecting immunological status). All data on biomarkers will be presented graphically over time. RESULTS: No ethical approval will be required, as this review is based on published data and does not involve interaction with human participants. The search for this systematic review commenced in February 2021, and we expect to publish the findings in mid-2023. CONCLUSIONS: This study will provide the behavior profile of biomarkers for PSI and patients following elective surgery for degenerative spinal diseases from the preoperative period up to 90 days postoperative, providing cutoff values on the day of diagnosis. This research will provide clinicians with highly trustable cutoff reference values for PSI diagnosis. Finally, we expect to provide a basis for future research on biomarkers that help diagnose more accurately and in a timely manner in the early stages of illness, ultimately impacting the patient's physical and mental health, and reducing the disease burden. TRIAL REGISTRATION: PROSPERO CRD42022304645; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=304645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41555.

Design of a Rheumatology Transition Clinic for a Resource-Constrained Setting.

OBJECTIVES: To describe the design process of a medical care program for adolescents with pediatric onset rheumatic diseases (PRD) during the transition from pediatric to adult care in a resource-constrained hospital. METHODS: The model of attention was developed in three steps: 1) the selection of a multidisciplinary team, 2) the evaluation of the state of readiness of patients and caregivers for the transition, and 3) the design of a strategy of attention according to local needs. The results of the first two steps were used in order to develop the strategy of attention. RESULTS: The transition process was structured in three stages: pretransition (at pediatric rheumatology clinic), Transition Clinic for Adolescents with Rheumatic Diseases (TCARD, the main intervention), and post-transition (at adult rheumatology clinic). Each stage was divided, in turn, into a variable number of phases (8 in total), which included activities and goals that patients and caregivers were to accomplish during the process. A multidisciplinary approach was planned by pediatric and adult rheumatologists, nutritionists, physiatrists, psychiatrist, psychologist, nurse, and social worker. During TCARD, counseling, education, nutritional, physical, and mental health interventions were considered. CONCLUSIONS: The proposed transition model for patients with rheumatic diseases can be a useful tool in developing countries.

Development of a Portland Cement-Based Material with Agave salmiana Leaves Bioaggregate.

Depending on the morphology of the natural fibers, they can be used as reinforcement to improve flexural strength in cement-based composites or as aggregates to improve thermal conductivity properties. In this last aspect, hemp, coconut, flax, sunflower, and corn fibers have been used extensively, and further study is expected into different bioaggregates that allow diversifying of the raw materials. The objective of the research was to develop plant-based concretes with a matrix based on Portland cement and an aggregate of Agave salmiana (AS) leaves, obtained from the residues of the tequila industry that have no current purpose, as a total replacement for the calcareous aggregates commonly used in the manufacturing of mortars and whose extraction is associated with high levels of pollution, to improve their thermal properties and reduce the energy demand for air conditioning in homes. Characterization tests were carried out on the raw materials and the vegetal aggregate was processed to improve its compatibility with the cement paste through four different treatments: (a) freezing (T/C), (b) hornification (T/H), (c) sodium hydroxide (T/NaOH), and (d) solid paraffin (T/P). The effect of the treatments on the physical properties of the resulting composite was evaluated by studying the vegetal concrete under thermal conductivity, bulk density, and compressive strength tests with a volumetric ratio between the vegetal aggregate and the cement paste of 0.36 and a water/cement ratio of 0.35. The hornification treatment showed a 15.2% decrease in the water absorption capacity of the aggregate, resulting in a composite with a thermal conductivity of 0.49 W/mK and a compressive strength of 8.66 MPa, which allows its utilization as a construction material to produce prefabricated blocks.

Creencias de enfermedad, creencias de medicación y adherencia al tratamiento en pacientes con hipertensión arterial / Disease belief, medication belief and adherence to treatment in patients with high blood pressure

Resumen Objetivo: Comparar las creencias de enfermedad y las creencias de medicación con la adherencia al tratamiento en pacientes con hipertensión arterial. Método: Diseño transversal comparativo en población hipertensa sin diabetes mellitus, grupo de 137 pacientes adherentes y grupo de 129 pacientes no adherentes. Se evaluaron las creencias de la enfermedad y las creencias de la medicación. El análisis estadístico incluyó prueba de ji al cuadrado, razón de momios e intervalo de confianza para razón de momios. Resultados: En el grupo de pacientes adherentes, el 71.5% tienen creencias adecuadas de la enfermedad, y en el grupo de pacientes no adherentes el 43.4% también tienen creencias adecuadas de la enfermedad (p = 0.000). Cuando se agrupan las creencias de la enfermedad y las creencias sobre la medicación existe una asociación con la adherencia al tratamiento en los pacientes hipertensos. Conclusiones: Existe asociación entre las creencias de la enfermedad y las creencias de la medicación con la adherencia al tratamiento antihipertensivo.

Abstract Objective: Compare disease beliefs and medication beliefs with adherence to treatment in patients with hypertension without diabetes mellitus. Method: Comparative transverse design in hypertensive population, a group of 137 adherent patients and a group of 129 non-adherent patients. The beliefs of the disease and beliefs about the medication were evaluated. The statistical analysis included chi squared, odds ratio and confidence interval for odds ratio. Results: In the group of adherent patients, 71.5% have an adequate belief of the disease and in the group of non-adherent patients, 43.4% also have an adequate belief of the disease (p = 0.000). When the belief of the disease and beliefs about the medication are grouped, there is an association with adherence to treatment in hypertensive patients. Conclusions: There is an association between beliefs about the disease and medication with adherence to antihypertensive treatment.

Cabozantinib plus atezolizumab versus sorafenib for advanced hepatocellular carcinoma (COSMIC-312): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Cabozantinib has shown clinical activity in combination with checkpoint inhibitors in solid tumours. The COSMIC-312 trial assessed cabozantinib plus atezolizumab versus sorafenib as first-line systemic treatment for advanced hepatocellular carcinoma. METHODS: COSMIC-312 is an open-label, randomised, phase 3 trial that enrolled patients aged 18 years or older with advanced hepatocellular carcinoma not amenable to curative or locoregional therapy and previously untreated with systemic anticancer therapy at 178 centres in 32 countries. Patients with fibrolamellar carcinoma, sarcomatoid hepatocellular carcinoma, or combined hepatocellular cholangiocarcinoma were not eligible. Tumours involving major blood vessels, including the main portal vein, were permitted. Patients were required to have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), Barcelona Clinic Liver Cancer stage B or C disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ and marrow function, and Child-Pugh class A. Previous resection, tumour ablation, radiotherapy, or arterial chemotherapy was allowed if more than 28 days before randomisation. Patients were randomly assigned (2:1:1) via a web-based interactive response system to cabozantinib 40 mg orally once daily plus atezolizumab 1200 mg intravenously every 3 weeks, sorafenib 400 mg orally twice daily, or single-agent cabozantinib 60 mg orally once daily. Randomisation was stratified by disease aetiology, geographical region, and presence of extrahepatic disease or macrovascular invasion. Dual primary endpoints were progression-free survival per RECIST 1.1 as assessed by a blinded independent radiology committee in the first 372 patients randomly assigned to the combination treatment of cabozantinib plus atezolizumab or sorafenib (progression-free survival intention-to-treat [ITT] population), and overall survival in all patients randomly assigned to cabozantinib plus atezolizumab or sorafenib (ITT population). Final progression-free survival and concurrent interim overall survival analyses are presented. This trial is registered with ClinicalTrials.gov, NCT03755791. FINDINGS: Analyses at data cut-off (March 8, 2021) included the first 837 patients randomly assigned between Dec 7, 2018, and Aug 27, 2020, to combination treatment of cabozantinib plus atezolizumab (n=432), sorafenib (n=217), or single-agent cabozantinib (n=188). Median follow-up was 15·8 months (IQR 14·5-17·2) in the progression-free survival ITT population and 13·3 months (10·5-16·0) in the ITT population. Median progression-free survival was 6·8 months (99% CI 5·6-8·3) in the combination treatment group versus 4·2 months (2·8-7·0) in the sorafenib group (hazard ratio [HR] 0·63, 99% CI 0·44-0·91, p=0·0012). Median overall survival (interim analysis) was 15·4 months (96% CI 13·7-17·7) in the combination treatment group versus 15·5 months (12·1-not estimable) in the sorafenib group (HR 0·90, 96% CI 0·69-1·18; p=0·44). The most common grade 3 or 4 adverse events were alanine aminotransferase increase (38 [9%] of 429 patients in the combination treatment group vs six [3%] of 207 in the sorafenib group vs 12 [6%] of 188 in the single-agent cabozantinib group), hypertension (37 [9%] vs 17 [8%] vs 23 [12%]), aspartate aminotransferase increase (37 [9%] vs eight [4%] vs 18 [10%]), and palmar-plantar erythrodysaesthesia (35 [8%] vs 17 [8%] vs 16 [9%]); serious treatment-related adverse events occurred in 78 (18%) patients in the combination treatment group, 16 (8%) patients in the sorafenib group, and 24 (13%) in the single-agent cabozantinib group. Treatment-related grade 5 events occurred in six (1%) patients in the combination treatment group (encephalopathy, hepatic failure, drug-induced liver injury, oesophageal varices haemorrhage, multiple organ dysfunction syndrome, and tumour lysis syndrome), one (<1%) patient in the sorafenib group (general physical health deterioration), and one (<1%) patient in the single-agent cabozantinib group (gastrointestinal haemorrhage). INTERPRETATION: Cabozantinib plus atezolizumab might be a treatment option for select patients with advanced hepatocellular carcinoma, but additional studies are needed. FUNDING: Exelixis and Ipsen.

Spotted Fever: An Undercover Cause of Hemophagocytic Lymphohistiocytosis in the Immediate Postpartum.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by a dysregulated activation of the immune system that causes fever, cytopenias, organomegalies, and hemophagocytosis. There are infectious, neoplastic, rheumatologic, and miscellaneous causes. Rickettsioses are a neglected cause of HLH. We report a confirmed case of an immunocompetent woman in Mexico with postpartum HLH secondary to spotted fever. We did a review of the literature for search of similar cases. The association between these two diseases was found in postmortem studies, unrelated to postpartum. This diagnosis should be considered in all patients with HLH without an evident cause in areas of epidemiological risk.

Disease belief, medication belief and adherence to treatment in patients with high blood pressure / Creencias de enfermedad, creencias de medicación y adherencia al tratamiento en pacientes con hipertensión arterial

Objective: Compare disease beliefs and medication beliefs with adherence to treatment in patients with hypertension without diabetes mellitus. Method: Comparative transverse design in hypertensive population, a group of 137 adherent patients and a group of 129 non-adherent patients. The beliefs of the disease and beliefs about the medication were evaluated. The statistical analysis included chi squared, odds ratio and confidence interval for odds ratio. Results: In the group of adherent patients, 71.5% have an adequate belief of the disease and in the group of non-adherent patients, 43.4% also have an adequate belief of the disease (p = 0.000). When the belief of the disease and beliefs about the medication are grouped, there is an association with adherence to treatment in hypertensive patients. Conclusions: There is an association between beliefs about the disease and medication with adherence to antihypertensive treatment.

Objetivo: Comparar las creencias de enfermedad y las creencias de medicación con la adherencia al tratamiento en pacientes con hipertensión arterial. Método: Diseño transversal comparativo en población hipertensa sin diabetes mellitus, grupo de 137 pacientes adherentes y grupo de 129 pacientes no adherentes. Se evaluaron las creencias de la enfermedad y las creencias de la medicación. El análisis estadístico incluyó prueba de ji al cuadrado, razón de momios e intervalo de confianza para razón de momios. Resultados: En el grupo de pacientes adherentes, el 71.5% tienen creencias adecuadas de la enfermedad, y en el grupo de pacientes no adherentes el 43.4% también tienen creencias adecuadas de la enfermedad (p = 0.000). Cuando se agrupan las creencias de la enfermedad y las creencias sobre la medicación existe una asociación con la adherencia al tratamiento en los pacientes hipertensos. Conclusiones: Existe asociación entre las creencias de la enfermedad y las creencias de la medicación con la adherencia al tratamiento antihipertensivo.

Symbiotic and toxinogenic Rhizopus spp. isolated from soils of different papaya producing regions in Mexico.

Mucoralean fungi from the genus Rhizopus are common inhabitants of terrestrial ecosystems, being some pathogens of animals and plants. In this study, we analyzed the symbiotic and toxinogenic potential of Rhizopus species derived from agricultural soils dedicated to the production of papaya (Carica papaya L.) in Mexico. Four representative strains of soil-derived Rhizopus spp. were analyzed employing molecular, microscopic, and metabolic methods. The ITS phylogenies identified the fungi as Rhizopus microsporus HP499, Rhizopus delemar HP475 and HP479, and Rhizopus homothallicus HP487. We discovered that R. microsporus HP499 and R. delemar HP475 harbor similar endofungal bacterial symbionts that belong to the genus Mycetohabitans (Burkholderia sensu lato) and that none of the four fungi were associated with Narnavirus RmNV-20S and RmNV-23S. Intriguingly, the interaction between R. delemar - Mycetohabitans showed different phenotypes from known R. microsporus - Mycetohabitans symbioses. Elimination of bacteria in R. delemar HP475 did not cause a detrimental effect on fungal growth or asexual reproduction. Moreover, metabolic and molecular analyses confirmed that, unlike symbiotic R. microsporus HP499, R. delemar HP475 does not produce rhizoxin, one of the best-characterized toxins produced by Mycetohabitans spp. The rhizoxin (rhi) biosynthetic gene cluster seems absent in this symbiotic bacterium. Our study highlights that the symbioses between Rhizopus and Mycetohabitans are more diverse than anticipated. Our findings contribute to expanding our understanding of the role bacterial symbionts have in the pathogenicity, biology and evolution of Mucorales.

Minimally Invasive Posterior Tubular Microsurgical Approach for the Management of Symptomatic Synovial Cysts of the Lumbar and Cervical Spine.

BACKGROUND: Synovial cysts are commonly associated with instability. Whether to fuse patients is a matter of controversy. Simple resection may offer favorable clinical outcomes but may come at the expense of recurrence rate. We describe our experience with the minimally invasive management of these lesions using microsurgical dissection through a tubular retractor system. MATERIALS: A retrospective cohort study of symptomatic patients with synovial cysts treated by a minimally invasive tubular approach from 2001 to 2018 was performed. We evaluated variables such as preexisting spinal pathology, previous surgery, radiological findings, comorbidities, and secondary surgery requiring fusion. We used the visual analog scale (VAS), the Oswestry disability index (ODI), and the Macnab scale for clinical evaluation. RESULTS: There were 35 patients with a mean age of 63 years. The mean duration of symptoms before surgery was 195 weeks. Axial pain was present in 77.1% of cases; radiculopathy was the main symptom in 94.3% of cases. The most frequent site was L4-L5 (62.8%). Presenting comorbidities were lumbar stenosis (28.6% of patients), spondylolisthesis (8.6%), and facet hypertrophy (31.4%). Mean surgical time was 143 minutes (range, 55-360 minutes). The mean hospital stay was 2 days, ranging from 1 to 5 days. No complications were encountered as a consequence of the surgical procedure. All patients showed neurophysiological improvement after surgical intervention. A total of 34 patients (97.14%) showed clinical improvement at the end of follow-up, averaging 17 months and ranging from 1 to 60 months, 28 patients (80%) had good to excellent Macnab outcomes, 6 patients (17.14%) were rated as fair, and 1 (2.86%) patient had a poor Macnab outcome. Radicular VAS significantly changed (P < .05) from a preoperative mean of 8.23 ± 1.24 to a postoperative mean of 2.23 ± 1.94. ODI significantly decreased (P < .05) from a preoperative of mean of 41.02 ± 12.56 to a postoperative of mean of 11.82 ± 10.56. We performed fusion at initial surgery in 37.1% of cases; however, 3 more patients required secondary fusion at follow-up. CONCLUSION: Our series corroborates the prior literature with a low incidence of synovial cysts in the cervical spine and none in the thoracic spine. The present work shows the efficacy of minimally invasive surgery in the treatment of these lesions. Synovial cysts were associated with instability, ultimately requiring fusion in the majority of patients. The authors' study includes a large patient series with minimally invasive microsurgical decompression performed through a tubular retractor to date. LEVEL OF EVIDENCE: 3.