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Diego Arauna,1,* Alvaro Cerda,2,3,* José Francisco García-García,4 Sergio Wehinger,1 Felipe Castro,5 Diego Méndez,1 Marcelo Alarcón,1 Eduardo Fuentes,1,2 Iván Palomo1,2 1Thrombosis Research Center, Department of Clinical Biochemistry and Immunohematology, Faculty of Health Sciences, Interdisciplinary Excellence Research Program on Healthy Aging (PIEI-ES), Interdisciplinary Center on Aging, Universidad de Talca, Talca, Chile; 2Thematic Task Force on Healthy Aging, CUECH Research Network, Viña Del Mar, Chile; 3Center of Excellence in Translational Medicine, CEMT-BIOREN, Department of Basic Sciences, Universidad de la Frontera, Temuco, Chile; 4Department of Geriatric Medicine, Complejo Hospitalario de Toledo, Toledo, Spain; 5School of Medicine, Universidad de Talca, Talca, Chile*These authors contributed equally to this workCorrespondence: Eduardo Fuentes; Iván Palomo Email edfuentes@utalca.cl; ipalomo@utalca.clAim: To analyze the relationship between polypharmacy and variables as frailty and other chronic comorbidities in Chilean older adults.Design: Cross-sectional study.Participants: One thousand two hundred and five older adults aged 65 and older.Methods: The presence or absence of frailty syndrome was determined according to Fried criteria. Data collection was made through questionnaires conducted by an interview.Results: The prevalence of polypharmacy was 37.59%. The prevalence of hyperpolypharmacy was 2%. Increased prevalence of frailty was demonstrated regarding the progression of the state of polypharmacy. When analyzing the contribution of frailty respect polypharmacy condition, frail state, nutritional risk and obesity are founded as a factor associated with polypharmacy. Regarding chronic disease, hypertension (OR: 8.039, p< 0.0001), type 2 diabetes (OR: 4.001, p< 0.0001) and respiratory diseases (OR: 2.930, p< 0.0001) were associated to polypharmacy. It was found a strong and significant positive correlation between polypharmacy prevalence and frailty score (polypharmacy condition, Spearman R: 0.89, p=0.033; hyperpolypharmacy condition, Spearman R: 0.94, p=0.016). When analyzing the contribution of the polypharmacy to the presence of frailty, polypharmacy condition (OR: 1.510, p< 0.05), cognitive impairment (OR: 3.887, p< 0.001), obesity (OR: 1.560, p< 0.01) and nutritional risk (OR: 2.590, p< 0.001) are associated to frailty.Conclusion: Frailty and chronic conditions as nutritional risk, obesity, hypertension, type 2 diabetes and respiratory disease are an important risk factor for the development of polypharmacy in Chilean older adults. Likewise, polypharmacy condition was observed to be a risk factor for frailty, demonstrating the bidirectional relationship between both conditions. Frailty syndrome evaluation in Chilean older adults could be an important alternative for polypharmacy prevention.Keywords: frailty, polypharmacy, chronic disease, older adults, aging

Competing Interests: The authors have no conflicts of interest to declare.

The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy., (© 2023. The Author(s).)

Objective: The purpose was to compare the outcomes of patients with ST-elevation myocardial infarction and multivessel coronary artery disease undergoing one-time multivessel revascularization (OTMVR) versus in-hospital staged complete revascularization with percutaneous coronary intervention., Methods: This was a single-center, retrospective, observational, and cohort study, including data from January 2013 to April 2019. A total of 634 patients were included in the study. Comparisons were made between patients who underwent in-hospital staged complete revascularization versus OTMVR. The primary endpoint was all-cause in-hospital mortality, secondary endpoints included cardiovascular complications, all-cause new hospitalization, and mortality evaluated at 30 days and 1 year. In addition, we constructed a logistic regression model for determining the risk factors that predicted mortality., Results: Of the 634 patients, 328 were treated with staged revascularization and 306 with OTMVR. About 76.7% were men, with a mean age of 63.3 years. Less complex coronary lesions and a higher proportion of the left anterior descending artery as the culprit vessel were found in the OTMVR group. Compared with staged revascularization, the primary and secondary endpoints occurred less frequently with OTMVR strategy., Conclusions: OTMVR did not generate more complications and demonstrate better clinical outcomes than in-hospital staged revascularization.

Trigeminal trophic syndrome is a rare condition characterized by self-inflicted persistent facial ulceration. It is believed to be consequent to central or peripheral insult to trigeminal nerve, which may have taken place even years before the ulcer development. The aggression to the nerve pathway causes dysesthesias in the trigeminal dermatomes that induce a self-mutilating behavior, with repetitive pinching or scratching in order to mitigate the altered sensation. Due to associated skin anesthesia, the patient does not interrupt manipulation of the affected area despite severe skin necrosis. Ulceration typically occurs in the ala nasi and may resemble other more common cutaneous diseases, such as tumors or infections. Given that this condition is not included in our daily clinical practice, the risk is that of a diagnostic delay with devastating functional and esthetic facial consequences. We present the case of a patient with a history of meningioma resection who developed this syndrome and we have reviewed the published literature to provide an update on the etiopathogenesis, diagnosis and treatment of this rare condition., (Copyright © 2022 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.)

Many studies that assess efficiency in health systems are based on output mean values. That approach ignores the representativeness of the average statistic, which can become a serious problem in estimation. To solve this question, this research contributes in three different ways: the first aim is to evaluate the technical efficiency in the management of European health systems considering a set of DEA (Data Envelopment Analysis) and FDEA (Fuzzy Data Envelopment Analysis) models. A second goal is to assess the bias in the estimation of efficiency when applying the conventional DEA. The third objective is the evaluation of the statistical relationship between the bias in the efficiency estimation and the macroeconomic variables (income inequality and economic freedom). The main results show positive correlations between DEA and FDEA scores. Notwithstanding traditional DEA models overestimate efficiency scores. Furthermore, the size of the bias is positively related to income inequality and negative with economic freedom in the countries evaluated.

Thymocyte selection-associated high-mobility group box (TOX) is a DNA-binding factor that is able to regulate transcription by modifying local chromatin structure and modulating the formation of multi-protein complexes. TOX has multiple roles in the development of the adaptive immune system including development of CD4 T cells, NK cells and lymph node organogenesis. However very few antibodies recognizing this molecule have been reported and no extensive study of the expression of TOX in reactive and neoplastic lymphoid tissue has been performed to date. In the present study, we have investigated TOX expression in normal and neoplastic lymphoid tissues using a novel rat monoclonal antibody that recognizes its target molecule in paraffin-embedded tissue sections. A large series of normal tissues and B- and T-cell lymphomas was studied, using whole sections and tissue microarrays. We found that the majority of precursor B/T lymphoblastic, follicular and diffuse large B-cell lymphomas, nodular lymphocyte-predominant Hodgkin lymphomas and angioimmunoblastic T-cell lymphomas strongly expressed the TOX protein. Burkitt and mantle cell lymphomas showed TOX expression in a small percentage of cases. TOX was not found in the majority of chronic lymphocytic leukemia, myelomas, marginal zone lymphomas and classical Hodgkin lymphomas. In conclusion, we describe for the first time the expression of TOX in normal and neoplastic lymphoid tissues. The co-expression of TOX and PD-1 identified in normal and neoplastic T cells is consistent with recent studies identifying TOX as a critical regulator of T-cell exhaustion and a potential immunotherapy target. Its differential expression may be of diagnostic relevance in the differential diagnosis of follicular lymphoma, the identification of the phenotype of diffuse large B-cell lymphoma and the recognition of peripheral T-cell lymphoma with a follicular helper T phenotype., Competing Interests: The authors have declared that no competing interests exist.

Introduction: The intra-aortic balloon pump (IABP) is used to prevent complications after coronary artery bypass grafting (CABG) surgery, although some results are controversial and basal ventricular function may play a role. This study assessed the benefit of preoperative use of IABP, as stratified by the ventricular function, in a population submitted to high-surgical-risk CABG., Methods: Patients >18 years old, with multiple coronary artery disease and thus candidates for CABG, were included. Cardiogenic shock, acute myocardial infarction (AMI), acute ventricle mechanical dysfunction, severe aortic regurgitation, tachyarrhythmia, massive pulmonary embolism, coagulopathy, or low life expectancy were exclusion criteria., Results: One hundred and twenty-nine patients aged 65 years old with hypertension, dyslipidemia, type 2 diabetes mellitus, and mean left ventricular ejection fraction (LVEF) 46% constituted the study population. No difference was observed at 30-day mortality endpoint (IABP vs. no IABP, 17 vs. 24%, OR 0.63, p = 0.20; AMI 25 vs. 31%, OR 0.75, p = 0.29). After LVEF stratification, the subgroup of 48 (75%) patients under IABP support and LVEF >35% had a reduced 30-day mortality risk (LVEF ≤35% vs. LVEF >35%, 37.5 vs. 10.4%, OR 0.3, p = 0.03), independently from potential confounders and showing an interaction with European System for Cardiac Operative Risk Evaluation-II (EuroSCORE-II). At secondary endpoints, IABP use was associated with a lower prevalence of acute renal failure and renal replacement therapy, but with a longer stay in the intensive care unit and longer hospitalization time., Conclusion: The preoperative use of IABP was associated with an independent reduction of 30-day mortality risk in cases with LVEF >35% in a population submitted to high-surgical-risk CABG. Likewise, the use of IABP was associated with a lower risk of postoperative renal complications., (© 2020 S. Karger AG, Basel.)

Heart failure (HF) is the leading cause of death worldwide. Efforts to decrease HF mortality rates include a multidisciplinary approach management. Although evidence suggests that this has been an optimal strategy for treating HF, the model remains not widely implanted. The current article explores the rationale behind the formation of a Heart Team in a developing country and its development despite the lack of an allocated budget., (© 2016 S. Karger AG, Basel.)

Proteoglycans (PGs), including heparan sulfate forms, are important regulators of tumor progression. In the PGs biosynthetic process, the core protein is synthesized on a ribosomal template and the sugar chains are assembled post-translationally, one sugar at a time, starting with the linkage of xylose to a serine residue of the core protein and followed by galactosidation of the xylosylprotein. Hydrophobic xylopyranosides have been previously shown to prime heparan sulfate synthesis, a property that was required to cause growth inhibition of tumor cells. To know if the antiproliferative activity of synthetic xylopyranosides is related to their ability to act as "decoy acceptors" of xylosylprotein 4-β-galactosyltransferase, we have heterologously expressed the catalytic domain of the human β-1,4-GalT 7 and studied the ability of a variety of synthetic xylopyranoside derivatives to act as substrates or inhibitors of the recombinant enzyme.

Locally advanced cervical carcinoma had been treated with radiation therapy until 1999, when five different large clinical trials showed an overall survival benefit when chemotherapy was administered concomitantly with radiotherapy. The chemotherapy agents used in these trials were cisplatin, cisplatin combined with fluorouracil or hydroxyurea. Weekly cisplatin (40 mg/m(2)) achieved the best responses, even when compared with the combination with fluorouracil. These results led the United States National Cancer Institute (NCI) to recommend platinum-based chemotherapy for the treatment of locally advanced cervical carcinoma. Other cytotoxic agents have been tried in combination with radiotherapy for the management of the disease, including carboplatin, paclitaxel, gemcitabine and even topotecan. Gemcitabine has shown promising results and the combination of paclitaxel and carboplatin has proved safe and effective. However, to date, there has been no agent or combination of agents to have shown superiority over weekly cisplatin. Biologic agents such as bevacizumab, cetuximab, sorafenib and erlotinib are currently being tried in different trials in combination with radiotherapy and cisplatin. Celecoxib, a COX-2 inhibitor was evaluated in an RTOG study in combination with cisplatin and flourouracil with radiation therapy with no apparent effect on DFS and poor rates of locoregional control. Chemoradiation is the current standard therapy in locally advanced cervical carcinoma. The integration of novel agents will be established by the ongoing clinical trials.

A multienzyme system composed by recombinant dihydroxyacetone kinase from Citrobacter freundii, fuculose-1-phosphate aldolase and acetate kinase, allows a practical one-pot C-C bond formation catalysed by dihydroxyacetone phosphate-dependent aldolases from dihydroxyacetone and an aldehyde.

The growing demand for enantiomerically pure pharmaceuticals has impelled research on enzymes as catalysts for asymmetric synthetic transformations. However, the use of enzymes for this purpose was rather limited until the discovery that enzymes can work in organic solvents. Since the advent of the PCR the number of available enzymes has been growing rapidly and the tailor-made biocatalysts are becoming a reality. Thus, it has been possible the use of enzymes for the synthesis of new innovative medicines such as carbohydrates and their incorporation to modern methods for drug development, such as combinatorial chemistry. Finally, the genomic research is allowing the manipulation of whole genomes opening the door to the combinatorial biosynthesis of compounds. In this review, our intention is to highlight the main landmarks that have led to transfer the chemical efficiency shown by the enzymes in the cell to the synthesis of bioactive molecules in the lab during the last 20 years.

A case of gaseous gangrene by Clostridium septicum associated with colorectal cancer is presented. The patient evolved rapidly towards septic shock and death. Autopsy showed occult neoplasm and pelvic and retroperitoneal myonecrosis. An exceptional finding was that of myocarditis in which thick gram-positive bacilli were identified. A review of the literature was carried out regarding the pathogenesis and clinical manifestations of this disease. The association of colonic neoplasm and Clostridium septicum may be related with the sensitivity of the cells of this neoplasm to the toxins of the microorganisms. The usefulness of this cytotoxicity is being tested in the therapeutic reduction of tumoral mass. With respect to clinical attitude, all the authors agree on the need for clinical suspicion as to the possible existence of occult colon neoplasm in individuals with septic shock by gaseous gangrene with no obvious entry site. Diagnosis is performed by imaging techniques with barium enema and if this is normal colonoscopy is carried out. Emergency treatment consists in laparotomy with resection of the neoplasm and debridement of the area accompanied by hyperbaric oxygen and antibiotics.

The case of a young female diagnosed with an IgG deficit and hepatic granulomas is presented. After 6 years of follow up the patient remains asymptomatic without treatment and with moderate biochemical cholestasis. The tests performed did not lead to a definitive etiologic diagnosis, therefore, according to a review of the literature, we believe that the granulomatous reactions are related with the hypogammaglobulinemia itself.

Galactorrhea as the result of hyperprolactinemia has been described in very rare cases associated to acute outbreaks of intermittent acute porphyria (IAP). In our country, any of such cases have been published or analytically documented. We present the case of a patient admitted in our hospital for the study of abdominal pain and galactorrhea, with latter diagnosis of IAP, supported by the assessment of the activity of the enzyme showing a deficit in the red blood cells.