Monastrol suppresses invasion and metastasis in human colorectal cancer cells by targeting fascin independent of kinesin-Eg5 pathway.

Rearrangement of the actin cytoskeleton is a prerequisite for carcinoma cells to develop cellular protrusions, which are required for migration, invasion, and metastasis. Fascin is a key protein involved in actin bundling and is expressed in aggressive and invasive carcinomas. Additionally, fascin appears to be involved in tubulin-binding and microtubule rearrangement. Pharmacophoric-based in silico screening was performed to identify compounds with better fascin inhibitory properties than migrastatin, a gold-standard fascin inhibitor. We hypothesized that monastrol displays anti-migratory and anti-invasive properties via fascin blocking in colorectal cancer cell lines. Biophysical (thermofluor and ligand titration followed by fluorescence spectroscopy), biochemical (NMR), and cellular assays (MTT, invasion of human tissue), as well as animal model studies (zebrafish invasion) were performed to characterize the inhibitory effect of monastrol on fascin activity. In silico analysis revealed that monastrol is a potential fascin-binding compound. Biophysical and biochemical assays demonstrated that monastrol binds to fascin and interferes with its actin-bundling activity. Cell culture studies, including a 3D human myoma disc model, showed that monastrol inhibited fascin-driven cytoplasmic protrusions as well as invasion. In silico, confocal microscopy, and immunoprecipitation assays demonstrated that monastrol disrupted fascin-tubulin interactions. These anti-invasive effects were confirmed in vivo. In silico confocal microscopy and immunoprecipitation assays were carried out to test whether monastrol disrupted the fascin-tubulin interaction. This study reports, for the first time, the in vitro and in vivo anti-invasive properties of monastrol in colorectal tumor cells. The number and types of interactions suggest potential binding of monastrol across actin and tubulin sites on fascin, which could be valuable for the development of antitumor therapies.

Efficacy of a Telemonitoring System as a Complementary Strategy in the Treatment of Patients With Heart Failure: Randomized Clinical Trial.

Episodes of decompensation are the main cause of hospital admissions in patients with heart failure. For this reason, the use of mobile apps emerges as an excellent strategy to improve coverage, real-time monitoring, and timeliness of care. ControlVit is an electronic application for early detection of complications studied within the context of a tertiary university hospital. Patients were randomized to the use of ControlVit versus placebo, during a 6-month follow-up. The primary outcome was the difference in numbers of readmissions and deaths for heart failure between both groups. One hundred forty patients were included (intervention = 71, placebo = 69), with an average age of 66 years old; 71% were men. The main etiology of heart failure was ischemic (60%), whereas the main comorbidities were arterial hypertension (44%), dyslipidemia (42%), hypothyroidism (38%), chronic kidney disease (38%), and diabetes mellitus (27%). The primary outcome occurred more frequently in the control group: readmission due to decompensation for heart failure (control group n = 14 vs intervention group n = 3; P = .0081), and death (control group n = 11 vs intervention group n = 3; P = .024). In heart failure patients, ControlVit is a useful and supplementary tool, which reduces hospital admissions due to episodes of decompensation.

Candida Variety in the Oral Cavity of Mexican Subjects with Type 2 Diabetes Mellitus and TLR2 Gene Expression.

BACKGROUND: The aim was to diagnose Candida in the oral cavity of subjects with type 2 diabetes mellitus (T2DM) using a genotyping technique and compare the results with those from conventional diagnosis by Papanicolaou (Pap) staining. METHODS: Palatal mucosa smears were performed on 18 dental care patients diagnosed with T2DM and grade I, II, and III prosthetic stomatitis who met the inclusion criteria; 18 healthy control subjects were also included in the study. Hemoglobin A1c (HbA1c) levels were determined from total blood. Using exfoliative cytology, the Pap staining technique was used to diagnose candidiasis. Exfoliative cytology was also used for molecular diagnosis; DNA was obtained for Candida genotyping, and RNA was used for gene expression studies. RESULTS: Clinical patterns indicated that all subjects were positive for Candida; however, Pap analysis revealed only three positive subjects, whereas end-point polymerase chain reaction (PCR) analysis revealed 15 subjects with some type of Candida. The most common Candida species found were Candida guilliermondii (38.8%), Candida krusei (33.3%), Candida tropicalis, and Candida lusitaniae (22.2%). Interestingly, the coexpression of different species of Candida was found in various patients. In all patients, HbA1c levels were increased. Gene expression analysis showed a significant decrease (p ≤ 0.05) in TLR2 expression in positive subjects, whereas TLR4 expression did not differ significantly among patients. CONCLUSIONS: The end-point PCR technique showed better sensitivity for the diagnosis of Candida when compared with the diagnosis by Pap staining. T2DM subjects showed an increased presence of C. guilliermondii that was correlated with decreased TLR2 expression.

Extraosseous Ewing's sarcoma of the pancreas.

We present the clinical case of a 21-year-old male with abdominal pain in the left hypochondrium radiating to the ipsilateral lumbar area and a weight loss of 2kg over a month, secondary to a large palpable intra-abdominal mass in the examination. TAC revealed a large solid mass with necrotic-cystic component which depended of the pancreas, infiltrated the spleen, enveloped the celiac trunk and affected to the splenic vases. Inmunohistochemical and molecular study confirmed the diagnosis extraosseus Ewing sarcoma (EES).

Perineural Infiltration: A Comprehensive Review of Diagnostic, Prognostic, and Therapeutic Implications.

ABSTRACT: Perineural infiltration refers to a neoplastic cell involvement in, around, and through the nerves. It is considered as one of the neoplastic dissemination pathways. Thus, its identification is crucial to establish the prognosis of some malignant skin neoplasms, such as squamous cell carcinoma, and explains the locally aggressive behavior of cutaneous neoplasms, such as microcystic adnexal carcinoma. We have conducted a review of malignant and benign skin tumors in which perineural infiltration has been described, and we also discuss some histopathological findings that may simulate perineural infiltration.

Impact of Pleural Lavage Cytology Positivity on Early Recurrence After Surgery for Non-Small Cell Lung Cancer.

OBJECTIVE: The aim of this study was to elucidate the impact of pleural lavage cytology positivity on early recurrence in patients operated on non-small cell lung cancer (NSCLC). METHODS: This is a multicentre prospective cohort study of 684 patients undergoing an anatomical lung resection for NSCLC between October 2015 and October 2017 at 12 national centres. A pleural lavage was performed before and after lung resection. The association between the different predictors of early recurrence and PLC positivity was performed using univariate and multivariate logistic regression models. A propensity score analysis was performed by inverse probability weighting (IPSW) using average treatment effect (ATE) estimation to analyse the impact of PLC positivity on early recurrence. RESULTS: Overall PLC positivity was observed in 15 patients (2.2%). After two years, 193 patients (28.2%) relapsed, 182 (27.2%) with a negative PLC and 11 (73.3%) with a positive PLC (p<0.001). Factors associated to early recurrence were adenocarcinoma histology (OR=1.59, 95%CI 1.06-2.38, p=0.025), visceral pleural invasion (OR=1.59, 95%CI 1.04-2.4, p=0.03), lymph node involvement (OR=1.84, 95%CI 1.14-2.96, p=0.013), advanced pathological stage (OR=2.12, 95%CI 1.27-3.54, p=0.004) and PLC positivity (OR=4.14, 95%CI 1.25-16.36, p=0.028). After IPSW, PLC positivity was associated with an increased risk of early recurrence (OR=3.46, 95%CI 2.25-5.36, p<0.001). CONCLUSIONS: Positive pleural lavage cytology was found to be the strongest predictor of early recurrence.

Dysphagia secondary to neuroendocrine carcinoma: a rare esophageal tumor.

We present two clinical cases, a 68-year-old male and a 55-year-old female, who are being studied for progressive solid food dysphagia. The initial gastroscopy revealed a polypoid lesion in the first case and a partially stenosing lesion in the second case. Both lesions were located in the mid-esophagus and presented a normal mucosa. Histological diagnosis confirmed an esophageal neuroendocrine carcinoma (NEC) of large cell and small cell types, respectively.

Relationship between the structure, function and endothelial damage, and vascular ageing and the biopsychological situation in adults diagnosed with persistent COVID (BioICOPER study). A research protocol of a cross-sectional study.

Background: SARS-CoV-2 infection affects the vascular endothelium, which mediates the inflammatory and thrombotic cascade. Moreover, alterations in the endothelium are related to arterial stiffness, which has been established as a marker of cardiovascular disease. The objective of this study is to analyse how the structure, vascular function, vascular ageing and endothelial damage are related to the biopsychological situation in adults diagnosed with persistent COVID and the differences by gender. Methods: This cross-sectional, descriptive, observational study will be carried out in the Primary Care Research Unit of Salamanca (APISAL) and in the BioSepsis laboratory of the University of Salamanca. The sample will be selected from the persistent COVID monographic office at the Internal Medicine Service of the University Hospital of Salamanca, and from the population of subjects diagnosed with persistent COVID in the clinical history of Primary Care. Through consecutive sampling, the study will include 300 individuals diagnosed with persistent COVID who meet the diagnosis criteria established by the WHO, after they sign the informed consent. Endothelial damage biomarkers will be measured using ELLA-SimplePlexTM technology (Biotechne). Their vascular structure and function will be analysed by measuring the carotid intima-media thickness (Sonosite Micromax); the pulse wave and carotid-femoral pulse wave velocity (cfPWV) will be recorded with Sphygmocor System®. Cardio Ankle Vascular Index (CAVI), brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index will be analysed with Vasera VS-2000®. The integral assessment of the subjects with persistent COVID will be conducted with different scales that evaluate fatigue, sleep, dyspnea, quality of life, attention, nutrition state, and fragility. We will also evaluate their lifestyles (diet, physical activity, smoking habits and alcohol consumption), psychological factors, and cognitive deterioration, which will be gathered through validated questionnaires; moreover, physical activity will be objectively measured using a pedometer for 7 days. Body composition will be measured through impedance using an Inbody 230. Vascular ageing will be calculated with 10 and 90 percentiles of cfPWV and baPWV. Furthermore, we will analyse the presence of vascular injury in the retina, heart, kidneys and brain, as well as cardiovascular risk. Demographic and analytical variables will also be gathered. Discussion: Arterial stiffness reflects the mechanic and functional properties of the arterial wall, showing the changes in arterial pressure, blood flow, and vascular diameter that occur with each heartbeat. SARS-CoV-2 affects the endothelial cells that are infected with this virus, increasing the production of pro-inflammatory cytokines and pro-thrombotic factors, which can cause early vascular ageing and an increase of arterial stiffness. Persistent COVID is a complex heterogeneous disorder that affects the lives of millions of people worldwide. The identifications of potential risk factors to better understand who is at risk of developing persistent COVID is important, since this would enable early and appropriate clinical support. It is unknown whether vascular alterations caused by COVID-19 resolve after acute infection or remain over time, favouring the increase of arterial stiffness and early vascular ageing. Therefore, it is necessary to propose studies that analyse the evolution of persistent COVID in this group of patients, as well as the possible variables that influence it. Clinical Trial registration: ClinicalTrials.gov, identifier NCT05819840.

Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines.

Breast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. In this study, through in vitro assays, it was observed that IA has similar cytotoxic activity between the subtypes triple negative, HER2+, and luminal A of the breast cancer cell lines. IA cytotoxic activity is higher in cancer than in nontumorigenic cells, and its selectivity index for cancer cells is more than that of the drug doxorubicin. Molecular docking and its in silico comparison with the 2-Deoxyglucose inhibitor suggest that IA could bind to Hexokinase II (HKII), decreasing its expression. Since we did not find changes in the expression of the glycolytic pathway, we suppose that IA could affect the antiapoptotic function of HKII in cancer cells. The IA-HKII union would activate the voltage-gated anion channel 1 (VDAC1), resuming apoptosis. Therefore, we suggest that IA could be used against almost any subtype and that its cytotoxic effect could be due to the reactivation of apoptosis in breast cancer cells.

Recognition of the interaction between the bioactive peptide Val-Pro-Pro and the minimal promoter region of genes SOD and CAT using QCM-D and docking studies.

Bioactive peptides are biomolecules involved in very diverse mechanisms in vivo. It has been reported that bioactive peptides play a very important role in the regulation of physiological functions such as oxidative stress, hypertension, cancer and inflammation. It's been reported that the milk derived peptide (VPP) prevents the progress of hypertension in different animal models and human beings with mild hypertension. It has also been shown that oral administration of VPP produces an anti-inflammatory effect in adipose tissue of mouse models. Currently there are no reports on the possible interaction of VPP with the enzymes superoxide dismutase (SOD) and catalase (CAT), the main regulators of oxidative stress. This study analyzes the interaction between VPP and specific domains in the minimal promoter region of the genes SOD and CAT in blood samples of obese children using a QCM-D type piezoelectric biosensor. We also used molecular modeling (docking) to determine the interaction between the peptide VPP and the minimal promoter region of both genes. With QCM-D, we detected the interaction of VPP with the nitrogenous base sequences that comprise the minimal promoter regions of both genes CAT and SOD. These experimental interactions were explained at the atomic level by molecular docking simulations showing how the peptides are capable of reaching the DNA structures by means of hydrogen bonds with favored free energy values. It is possible to conclude that the combined use of docking and QCM-D allows for the determination of the interaction of small peptides (VPP) with specific sequences of genes.

Role of SHP2 (PTPN11) in glycoprotein VI-dependent thrombus formation: Improved platelet responsiveness by the allosteric drug SHP099 in Noonan syndrome patients.

INTRODUCTION: The protein tyrosine phosphatase SHP2 (PTPN11) is a negative regulator of glycoprotein VI (GPVI)-induced platelet signal under certain conditions. Clinical trials with derivatives of the allosteric drug SHP099, inhibiting SHP2, are ongoing as potential therapy for solid cancers. Gain-of-function mutations of the PTPN11 gene are observed in part of the patients with the Noonan syndrome, associated with a mild bleeding disorder. Assessment of the effects of SHP2 inhibition in platelets from controls and Noonan syndrome patients. MATERIALS AND METHODS: Washed human platelets were incubated with SHP099 and stimulated with collagen-related peptide (CRP) for stirred aggregation and flow cytometric measurements. Whole-blood microfluidics assays using a dosed collagen and tissue factor coating were performed to assess shear-dependent thrombus and fibrin formation. Effects on clot formation were evaluated by thromboelastometry. RESULTS: Pharmacological inhibition of SHP2 did not alter GPVI-dependent platelet aggregation under stirring, but it enhanced integrin αIIbß3 activation in response to CRP. Using whole-blood microfluidics, SHP099 increased the thrombus buildup on collagen surfaces. In the presence of tissue factor and coagulation, SHP099 increased thrombus size and reduced time to fibrin formation. Blood from PTPN11-mutated Noonan syndrome patients, with low platelet responsiveness, after ex vivo treatment with SHP099 showed a normalized platelet function. In thromboelastometry, SHP2 inhibition tended to increase tissue factor-induced blood clotting profiles with tranexamic acid, preventing fibrinolysis. CONCLUSION: Pharmacological inhibition of SHP2 by the allosteric drug SHP099 enhances GPVI-induced platelet activation under shear conditions with a potential to improve platelet functions of Noonan syndrome patients.

Ocular and Palpebral Manifestations of Facial Palsy: An Epidemiologic Descriptive Study.

Purpose: We describe the ocular and periocular clinical features in patients with a facial palsy diagnosis of any etiology and to report the demographics, relevant medical history and treatment modalities in these patients. Patients and Methods: Retrospective and descriptive observational study. A total of 60 patients with a facial palsy diagnosis in the last 5 years were recruited from an ophthalmological clinic in northeastern Mexico. Demographic data, such as age, sex, disease evolution and etiology, visual acuity, ocular symptoms and ocular and periocular clinical features were obtained. Personal history of previous ophthalmologic surgery, as well as ocular and systemic diseases, were also recorded. Finally, a comparative analysis was done to determine association between signs, symptoms and treatment modalities. Results: A prevalence of 0.14% was reported, 56.7% of patients were female, and mean age of presentation was 55.63±17.2 years. 76.7% of facial palsy was idiopathic in origin, followed by vascular disease in 8.30% and iatrogenic in 6.70%. 40% of patients had a history of arterial hypertension, 36.3% were diabetic, and 6.70% had cerebrovascular disease. Conclusion: Early diagnosis of facial palsy is crucial in establishing an effective treatment plan and avoiding complications. The impact of this disease in patients' quality of life cannot be overlooked, and steps should be taken to address the different impairments that this ailment entails.

Amniotic Membrane Restores Chronic Wound Features to Normal in a Keratinocyte TGF-ß-Chronified Cell Model.

Unsuccessful wound closure in chronic wounds can be linked to altered keratinocyte activation and their inability to re-epithelize. Suggested mechanisms driving this impairment involve unbalanced cytokine signaling. However, the molecular events leading to these aberrant responses are poorly understood. Among cytokines affecting keratinocyte responses, Transforming Growth Factor-ß (TFG-ß) is thought to have a great impact. In this study, we have used a previously characterized skin epidermal in vitro model, HaCaT cells continuously exposed to TGF-ß1, to study the wound recovery capabilities of chronified/senescent keratinocytes. In this setting, chronified keratinocytes show decreased migration and reduced activation in response to injury. Amniotic membrane (AM) has been used successfully to manage unresponsive complicated wounds. In our in vitro setting, AM treatment of chronified keratinocytes re-enabled migration in the early stages of wound healing, also promoting proliferation at later stages. Interestingly, when checking the gene expression of markers known to be altered in TGF-ß chronified cells and involved in cell cycle regulation, early migratory responses, senescence, and chronic inflammation, we discovered that AM treatment seemed to reset back to keratinocyte status. The analysis of the evolution of both the levels of keratinocyte activation marker cytokeratin 17 and the spatial-temporal expression pattern of the proliferation marker Ki-67 in human in vivo biopsy samples suggests that responses to AM recorded in TGF-ß chronified HaCaT cells would be homologous to those of resident keratinocytes in chronic wounds. All these results provide further evidence that sustained TGF-ß might play a key role in wound chronification and postulate the validity of our TGF-ß chronified HaCaT in vitro model for the study of chronic wound physiology.

Síndrome de infusión de propofol y COVID-19. Reporte de caso / Propofol and COVID-19 infusion syndrome. Case report

Resumen: La forma grave de neumonía por SARS-CoV-2 (COVID-19) cursa en la mayoría de los casos con un síndrome de dificultad respiratoria aguda (SDRA). Es necesario emplear sedación durante su ventilación mecánica, el propofol es el que más de utiliza por su farmacocinética y farmacodinamia. El propofol es un anestésico que se usa ampliamente en las unidades de cuidados intensivos. Su empleo puede provocar un efecto adverso poco frecuente, pero en extremo grave, conocido como síndrome por infusión de propofol (SIP), el cual se encuentra estrechamente asociado a la velocidad de infusión aunado a factores de riesgos propios del paciente. Se caracteriza principalmente por inestabilidad hemodinámica, acidosis láctica y por progresión a disfunción multiorgánica. Se presenta un caso de SIP en paciente con síndrome de dificultad respiratoria aguda (SDRA) secundario a SARS-CoV-2 que desarrolla esta complicación asociada a la sedación. Se discute fisiopatológica clínica y consideraciones que deberán tomarse en cuenta al momento de su utilización en infusión continua.

Abstract: The severe form of SARS-CoV-2 pneumonia (COVID-19) occurs in most cases with acute respiratory distress syndrome (ARDS), requiring the use of sedation during mechanical ventilation, with propofol being the most widely used for its pharmacokinetics and pharmacodynamics. Propofol is a widely used anesthetic in intensive care units (ICU). Its use can cause an infrequent but extremely serious adverse effect, known as propofol infusion syndrome (PRIS), which is closely associated with the speed of infusion coupled with risk factors specific to the patient, the clinical features of PRIS are hemodynamic instability, lactic acidosis and with progression to multi-organ dysfunction. We present a case of SIP in a patient with acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 who develops this complication associated with sedation, discusses clinical pathophysiology and considerations that should be taken into account when using it in continuous infusion.

Noninvasive detection of microsatellite instability in patients with endometrial cancer.

The analysis of mismatch repair proteins in solid tissue is the standard of care (SoC) for the microsatellite instability (MSI) characterization in endometrial cancer (EC). Uterine aspirates (UAs) or circulating-DNA (cfDNA) samples capture the intratumor heterogeneity and provide a more comprehensive and dynamic molecular diagnosis. Thus, MSI analysis by droplet-digital PCR (ddPCR) in UAs and cfDNA can provide a reliable tool to characterize and follow-up the disease. The UAs, paraffin-embedded tumor tissue (FFPE) and longitudinal plasma samples from a cohort of 90 EC patients were analyzed using ddPCR panel and compared to the SoC. A high concordance (96.67%) was obtained between the analysis of MSI markers in UAs and the SoC. Three discordant cases were validated as unstable by ddPCR on FFPE samples. Besides, a good overall concordance (70.27%) was obtained when comparing the performance of the ddPCR assay on UAs and cfDNA in high-risk tumors. Importantly, our results also evidenced the value of MSI analysis to monitor the disease evolution. MSI evaluation in minimally invasive samples shows great accuracy and sensitivity and provides a valuable tool for the molecular characterization and follow-up of endometrial tumors, opening new opportunities for personalized management of EC.

Villoglandular Pattern in HPV-associated Endocervical Adenocarcinoma is Associated With Excellent Prognosis: A Reappraisal of 31 Cases Using IECC and Silva Pattern Classification.

Villoglandular adenocarcinoma of the cervix is a rare histologic entity that typically develops in young women, characterized by an association with oral contraceptives and excellent prognosis, though this point is controversial. These tumors have not been studied in the context of the International Endocervical Adenocarcinoma Criteria and Classification (IECC) or Silva Pattern Classification. We analyzed 31 cases that met strict diagnostic criteria, including being completely excised with negative margins. These were categorized according to IECC and Silva Pattern Classification and the association with various pathologic parameters analyzed. Most patients were young with a mean age of 41.1 (range 25-79). There were 14 (45.2%) pattern A, 11 (35.5%) pattern B, and 6 (19.3%) pattern C cases. Only 1 of 22 patients (4.5%) presented with lymph node metastasis at the time of diagnosis (pattern C, stage IB1) and 3 (9.7%) had lymphovascular invasion (2 pattern C, 1 pattern B). Overall survival was 100%, while recurrence-free survival was 96.2% for the entire cohort with only 1 case (3.2%) recurring 25 mo after surgery (IB2, pattern B). Kaplan Meier analysis (log rank test) revealed no significant correlation for recurrence-free survival at 5 and 10 yr associated with depth of invasion, tumor size, Silva pattern, FIGO stage, lymphovascular invasion, or lymph node metastasis. Cox univariate analysis demonstrated no independent prognostic factors predicting recurrence-free survival. These results indicate that completely excised villoglandular adenocarcinoma generally has an excellent prognosis and when Silva Pattern Classification is applied, those tumors that potentially have a higher chance for adverse outcomes can be identified.

Colchicine as rescue treatment in two pediatric patients with chronic recurrent multifocal osteomyelitis (CRMO).

Chronic recurrent multifocal osteomyelitis (CRMO) is a rare idiopathic autoinflammatory bone disease characterised by noninfective inflammation of bones. Diagnostic approach is challenging and requires exclusion of other causes such as malignancies or infections. Nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids are usually applied as first-line therapy in CRMO patients; however, some cases require more intensive therapy with second-line agents to control disease activity. We hereby describe the use of colchicine as a nonconventional second-line disease-modifying antirheumatic drug in two pediatric patients with CRMO refractory to NSAIDs and corticosteroids. Our data indicate that colchicine might prove an important area for future research as a potential therapeutic option with easy administration, low cost, and a good safety profile in CRMO patients refractory to first-line therapy.

O Prolongamento do Intervalo QTc na Admissão está Associado ao Aumento da Mortalidade em Pacientes com SARS-COV-2 durante a Hospitalização / Prolongation of the QTc Interval at Admission is Associated with Increased Mortality in Patients with SARS-COV-2 during Hospitalization

Resumo Fundamento O envolvimento cardiovascular associado à infecção por SARS-COV-2 está relacionado a desfechos desfavoráveis durante a internação. Portanto, a medida na admissão do intervalo QTc no eletrocardiograma de 12 derivações pode ser um marcador prognóstico. Objetivo Identificar a relação entre o prolongamento do QTc na admissão durante a hospitalização e a mortalidade por SARS-COV-2. Método Estudo observacional baseado em uma coorte retrospectiva de pacientes com infecção confirmada por SARS-COV-2 do Hospital Universitário San Ignacio, Bogotá (Colômbia), entre 19 de março de 2020 e 31 de julho de 2021. A mortalidade foi comparada em pacientes com QTc prolongado e normal na admissão e controle das variáveis clínicas e comorbidades por meio de modelos de regressão logística bivariada e multivariada. Um valor de p <0,05 foi considerado estatisticamente significativo Resultados Foram analisados 1.296 pacientes e 127 (9,8%) apresentaram QTc prolongado. A mortalidade foi maior em pacientes com QTc prolongado (39,4% vs. 25,3%, p=0,001), assim como o tempo de internação (mediana 11 vs. 8 dias; p=0,002). Na análise multivariada, a mortalidade foi associada a QTc prolongado (OR 1,61, IC 95%: 1,02; 2,54, p=0,038), idade (OR 1,03, IC 95% 1,02; 1,05, p<0,001), sexo masculino (OR 2,15, IC 95% 1,60; 2,90, p<0,001), doença renal (OR 1,32, IC 95% 1,05; 1,66, p=0,018) e índice de comorbidade de Charlson > 3 (OR 1,49, IC 95% 1,03; 2,17, p=0,035). Conclusões A mortalidade hospitalar por SARS-COV-2 está associada ao prolongamento do intervalo QTc no momento da admissão, mesmo após ajuste para idade, sexo, comorbidades e gravidade basal da infecção. Pesquisas adicionais são necessárias para estabelecer se esses achados estão relacionados ao envolvimento cardíaco pelo vírus, hipóxia e inflamação sistêmica.

Abstract Background Cardiovascular involvement associated with SARS-COV-2 infection is related to unfavorable outcomes during hospitalization. Therefore, the measurement at the admission of the QTc interval on the 12-lead electrocardiogram may be a prognostic marker. Objective To identify the relationship between QTc prolongation at admission during hospitalization and mortality from SARS-COV-2. Method Observational study based on a retrospective cohort of patients with confirmed SARS-COV-2 infection from San Ignacio University Hospital, Bogotá (Colombia), between March 19, 2020, and July 31, 2021. Mortality was compared in patients with prolonged and normal QTc at admission after controlling by clinical variables and comorbidities using bivariate and multivariate logistic regression models. A p-value <0.05 was considered statistically significant. Results 1296 patients were analyzed, and 127 (9.8%) had prolonged QTc. Mortality was higher in patients with prolonged QTc (39.4% vs 25.3%, p=0.001), as was hospital stay (median 11vs.8 days; p=0.002). In the multivariate analysis, mortality was associated with prolonged QTc (OR 1.61, 95% CI: 1.02; 2.54, p=0.038), age (OR 1.03, 95% CI 1.02; 1.05, p<0.001), male sex (OR 2.15, 95% CI 1.60; 2.90, p <0.001), kidney disease (OR 1.32, 95% CI 1.05; 1.66, p =0.018) and Charlson comorbidity index > 3 (OR 1.49, 95% CI 1.03; 2.17, p=0.035). Conclusions Hospital mortality due to SARS-COV-2 is associated with prolonging the QTc interval at the time of admission, even after adjusting for age, sex, comorbidities, and basal severity of infection. Additional research is needed to establish whether these findings are related to cardiac involvement by the virus, hypoxia, and systemic inflammation.

Análisis comparativo de la acreditación de unidades médicas en Canadá, Chile, la Comunidad Autónoma de Andalucía, Dinamarca y México / Comparative analysis of the accreditation of medical facilities in Canada, Chile, the Autonomous Community of Andalusia, Denmark, and Mexico / Análise comparativa da acreditação de estabelecimentos de saúde no Canadá, Chile, Comunidade Autônoma da Andaluzia, Dinamarca e México

RESUMEN Objetivo. Contrastar las características del proceso de acreditación de establecimientos de salud en Canadá, Chile, la Comunidad Autónoma de Andalucía, Dinamarca y México, con el fin de identificar elementos comunes y diferencias, y las lecciones aprendidas que puedan ser de utilidad para otros países y regiones. Métodos. Estudio observacional, analítico y retrospectivo en el que se usaron fuentes secundarias de libre acceso sobre acreditación y certificación de establecimientos de salud durante el período 2019-2021 en estos países y regiones. Se describen las características generales del proceso de acreditación y sus respuestas a puntos clave del diseño de estos programas. Además, se generaron categorías de análisis para el avance en su implementación y su nivel de complejidad, y se resumen los resultados favorables y desfavorables informados. Resultados. Los componentes operativos del proceso de acreditación son peculiares de cada país, aunque comparten similitudes. El programa de Canadá es el único que contempla algún tipo de evaluación responsiva. Hay una amplia variación en la cobertura de establecimientos acreditados entre países (desde 1% en México a 34,7% en Dinamarca). Entre las lecciones aprendidas, se destacan la complejidad de aplicación del sistema mixto público-privado (Chile), el riesgo de una excesiva burocratización (Dinamarca) y la necesidad de incentivos claros (México). Conclusiones. Los programas de acreditación operan de forma peculiar en cada país o región, logran alcances diferentes y presentan problemáticas también diversas, de las que podemos aprender. Es necesario considerar los elementos que obstaculizan la implementación y generar adecuaciones para los sistemas de salud en cada país o región.

ABSTRACT Objective. To compare and contrast the characteristics of the accreditation process for health care facilities in Canada, Chile, the Autonomous Community of Andalusia (Spain), Denmark, and Mexico, in order to identify shared characteristics, differences, and lessons learned that may be useful for other countries and regions. Methods. An observational, analytical, retrospective study using open-access secondary sources on the accreditation and certification of health care facilities in 2019-2021 in these countries and regions. The general characteristics of the accreditation processes are described and comments are made on key aspects of the design of these programs. Additionally, analytical categories were created for degree of implementation and level of complexity, and the positive and negative results reported are summarized. Results. The operational components of the accreditation processes are country-specific, although they share similarities. The Canadian program is the only one that involves some form of responsive evaluation. There is a wide range in the percentage of establishments accredited from country to country (from 1% in Mexico to 34.7% in Denmark). Notable lessons learned include the complexity of application in a mixed public-private system (Chile), the risk of excessive bureaucratization (Denmark), and the need for clear incentives (Mexico). Conclusions. The accreditation programs operate in a unique way in each country and region, achieve varying degrees of implementation, and have an assortment of problems, from which lessons can be learned. Elements that hinder their implementation should be considered and adjustments made for the health systems of each country and region.

RESUMO Objetivo. Comparar as características do processo de acreditação de estabelecimentos de saúde no Canadá, Chile, Comunidade Autônoma da Andaluzia, Dinamarca e México, a fim de identificar elementos comuns e diferenças, bem como lições aprendidas que podem ser úteis para outros países e regiões. Métodos. Estudo observacional, analítico e retrospectivo usando fontes secundárias de livre acesso sobre acreditação e certificação de estabelecimentos de saúde durante o período 2019-2021 nos países e regiões supracitados. As características gerais do processo de acreditação e suas respostas a pontos-chave no delineamento de tais programas foram descritas. Além disso, foram geradas categorias de análise para o andamento de sua implantação e seu grau de complexidade, e os desfechos favoráveis e desfavoráveis relatados foram resumidos. Resultados. Os componentes operacionais do processo de acreditação são peculiares a cada país, embora compartilhem certas semelhanças. O programa canadense é o único que contempla algum tipo de avaliação responsiva. Houve grande variação entre países no percentual de estabelecimentos acreditados (de 1% no México a 34,7% na Dinamarca). Entre as lições aprendidas, destacam-se a complexidade da aplicação do sistema misto público-privado (Chile), o risco de burocratização excessiva (Dinamarca) e a necessidade de incentivos claros (México). Conclusões. Os programas de acreditação operam de forma peculiar em cada país ou região, têm diferentes escopos e também apresentam diversos problemas a partir dos quais podemos aprender. É preciso considerar os elementos que dificultam a implementação e realizar as adequações necessárias para os sistemas de saúde de cada país ou região.

Randomized double-blind clinical study in patients with COVID-19 to evaluate the safety and efficacy of a phytomedicine (P2Et).

Background: It has been proposed that polyphenols can be used in the development of new therapies against COVID-19, given their ability to interfere with the adsorption and entrance processes of the virus, thus disrupting viral replication. Seeds from Caesalpinia spinosa, have been traditionally used for the treatment of inflammatory pathologies and respiratory diseases. Our team has obtained an extract called P2Et, rich in polyphenols derived from gallic acid with significant antioxidant activity, and the ability to induce complete autophagy in tumor cells and reduce the systemic inflammatory response in animal models. Methods: In this work, a phase II multicenter randomized double-blind clinical trial on COVID-19 patients was designed to evaluate the impact of the P2Et treatment on the clinical outcome and the immunological parameters related to the evolution of the disease. The Trial was registered with the number No. NCT04410510*. A complementary study in an animal model of lung fibrosis was carried out to evaluate in situ lung changes after P2Et in vivo administration. The ability of P2Et to inhibit the viral load of murine and human coronaviruses in cellular models was also evaluated. Results: Patients treated with P2Et were discharged on average after 7.4 days of admission vs. 9.6 days in the placebo group. Although a decrease in proinflammatory cytokines such as G-CSF, IL-15, IL-12, IL-6, IP10, MCP-1, MCP-2 and IL-18 was observed in both groups, P2Et decreased to a greater extent G-CSF, IL-6 and IL-18 among others, which are related to lower recovery of patients in the long term. The frequency of T lymphocytes (LT) CD3+, LT double negative (CD3+CD4-CD8-), NK cells increased in the P2Et group where the population of eosinophils was also significantly reduced. In the murine bleomycin model, P2Et also reduced lung inflammation and fibrosis. P2Et was able to reduce the viral replication of murine and human coronaviruses in vitro, showing its dual antiviral and anti-inflammatory role, key in disease control. Conclusions: Taken together these results suggest that P2Et could be consider as a good co-adjuvant in the treatment of COVID-19. Clinical trail registration: https://clinicaltrials.gov/ct2/show/NCT04410510, identifier: NCT04410510.