Identifying locally actionable strategies to increase participant acceptability and feasibility to participate in Phase I cancer clinical trials.

BACKGROUND: Recruitment of cancer clinical trial (CCT) participants, especially participants representing the diversity of the US population, is necessary to create successful medications and a continual challenge. These challenges are amplified in Phase I cancer trials that focus on evaluating the safety of new treatments and are the gateway to treatment development. In preparation for recruitment to a Phase I recurrent head and neck cancer (HNC) trial, we assessed perceived barriers to participation or referral and suggestions for recruitment among people with HNC and community physicians (oncologist, otolaryngologist or surgeon). METHODS: Between December 2020 and February 2022, we conducted a qualitative needs assessment via semistructured interviews with a race and ethnicity-stratified sample of people with HNC (n = 30: 12 non-Hispanic White, 9 non-Hispanic African American, 8 Hispanic and 1 non-Hispanic Pacific Islander) and community physicians (n = 16) within the University of Florida Health Cancer Center catchment area. Interviews were analyzed using a qualitative content analysis approach to describe perspectives and identify relevant themes. RESULTS: People with HNC reported thematic barriers included: concerns about side effects, safety and efficacy; lack of knowledge and systemic and environmental obstacles. Physicians identified thematic barriers of limited physician knowledge; clinic and physician barriers and structural barriers. People with HNC and physicians recommended themes included: improved patient education, dissemination of trial information and interpersonal communication between community physicians and CCT staff. CONCLUSIONS: The themes identified by people with HNC and community physicians are consistent with research efforts and recommendations on how to increase the participation of people from minoritized populations in CCTs. This community needs assessment provides direction on the selection of strategies to increase CCT participation and referral. PATIENT OR PUBLIC CONTRIBUTION: This study focused on people with HNC and community physicians' lived experience and their interpretations of how they would consider a future Phase I clinical trial. In addition to our qualitative data reflecting community voices, a community member reviewed the draft interview guide before data collection and both people with HNC and physicians aided interpretation of the findings.

Vaginal Approach to Cesarean Section Scar Pregnancies: A Standardized Ten-step Surgical Procedure.

OBJECTIVE: To show a 10-step standardized vaginal surgical technique to treat first-trimester cesarean section scar pregnancies. DESIGN: A video article with a stepwise demonstration captured in an operation room of a tertiary medical center of a low-income country (Bolivia). SETTING: Cesarean section scar pregnancies have a wide variety of management options. We present a vaginal surgical approach that has been developed by our group with no observed complications in 6 consecutive cases at the time of this publication. INTERVENTIONS: A 10-step technique: (1) patient positioning, (2) cervical exposure and traction, (3) cervical infiltration with vasoconstrictor solution, (4) anterior mucosal incision and dissection of vesicovaginal space, (5) identification of vascular pedicle and ligation, (6) cold-knife isthmocele incision and ectopic pregnancy evacuation, (7) uterine cavity curettage, (8) hysterorrhaphy with interrupted suture, (9) cystoscopy, and (10) vaginal mucosa closure with running suture. We have used this technique in 6 consecutive patients. Operating time ranged between 20 and 25 minutes. All patients were discharged in postoperative day 1. CONCLUSION: We prefer surgical options for these patients because it provides both a complete removal of the ectopic pregnancy and repair of the isthmocele. A vaginal approach to such cases has proven to be a safe, simple, and fully reproductible technique. We find it applicable for any patient with this pathology but especially suitable for low-resource or somehow financially challenged hospitals.

Modulation of innate immune responses in the flame scallop Ctenoides scaber (Born, 1778) caused by exposure to used automobile crankcase oils.

The used automobile crankcase oils are potential sources of contaminant elements for the coastal-marine ecosystems, affecting mainly the immunological system of organisms that feed by filtration, e. g. scallops. This study examined the effects of a water-soluble fraction of used automobile crankcase oils (WSF-UACO) on innate cellular- and humoral immune responses of the flame scallop Ctenoides scaber. The scallops were exposed to ascending concentrations of 0, 0.001, 0.01, and 0.1 of WSF-UACO under a static system of aquaria during 7 and 13 d. The viability, haemocyte total count (HTC), lysosomal membrane destabilization (LMD), phagocytosis, and protein concentration in hemolymph samples withdrawn taken from the blood sinus as well as lysozyme activity of the digestive gland were measured as immune endpoints. A decrease in cellular immune competence in scallops exposed to WSF-UACO was observed, with significant impairment of viability, HTC, and phagocytosis. LMD index increased about exposure concentrations, and plasma protein concentrations augmented to 0.01 and 0.1% during 13 d. Lysozyme activity increased in scallops exposed to WSF-UVCO during 7 d, to level off in the chronic period. Lysozyme activity and enhanced plasma proteins could act as compensatory responses when cell parameters tend to fall, helping to the regulation of microbial microflora and possible invasion of pathogenic microbes as well as defense against xenobiotics. The results demonstrate that the immunological responses of C. scaber are highly sensitive to the complex chemical mixture of contaminants, and it could be used for evaluating biological risks of hazardous xenobiotics in tropical marine environments. Republic of Ecuador.

Polymorphisms of the TLR4 gene: Risk factor for chronicity and severity in oral vectorial Chagas disease.

Chagas disease is one of the parasitic infections with the greatest socio-economic impact in Latin America. In Venezuela, epidemiological data has shown different sources of infection, such as the vectorial route by oral transmission. Given the importance of the TLR4 gene in the innate immune response triggered by infection with Trypanosoma cruzi, this work analyses the role of TLR4 polymorphisms and its possible effect on cytokine expression. Genomic DNA was extracted from the peripheral blood of patients from the main outbreak of oral Chagas disease in Venezuela (n = 90), as well as from a group of healthy individuals (n = 183). Subsequently, peripheral blood was also extracted from individuals with different TLR4 haplotypes and then stimulated with LPS to determine the cytokine concentration by ELISA. The internalization of TLR4 was evaluated by flow cytometry. In comparison to healthy individuals, the analysis showed a significantly increased frequency of the Asp/Gly genotype in symptomatic patients. Also, observed a correlation of the 299/399 haplotype with a significant decrease in cytokine concentration and disease severity. Finally, the parasites' trypomastigotes cause the internalization or negative regulation of TLR4. The variants of TLR4 associated with low production of cytokines may be a risk factor for chronicity and severity (cardiac involvement) in oral vectorial Chagas disease.

Cr, Ni, and Zn removal from landfill leachate using vertical flow wetlands planted with Typha domingensis and Canna indica.

Chromium (Cr), Nickel (Ni), and zinc (Zn) removal from landfill leachate using mesocosm-scale vertical flow wetlands, the effect of recirculation, and the ability of macrophytes to retain metals were evaluated. Wetlands were filled with coarse sand and light expanded clay aggregates and planted with Typha domingensis or Canna indica. Wetlands were operated using intermittent loading, with and without recirculation. Raw leachate was diluted and spiked with metals to reach the following concentrations: 0.2 mg L-1 Cr , 0.2 mg L-1 Ni, and0.2 mg L-1 Zn and 1.0 mg L-1 Cr, 1.0 mg L-1 Ni, and 1.0 mg L-1 Zn. Wetlands planted with T. domingensis presented higher metal removal than those planted with C. indica. Recirculation enhanced metal removal efficiencies significantly, being for T. domingensis/C. indica: 60/54, 49/47, 61/47% for Cr, Ni, and Zn at 0.2 mg L-1, and 80/71, 76/62, 73/59% for Cr, Ni, and Zn at 1.0 mg L-1, respectively. Metals were efficiently retained by macrophytes. Plant biomass and metal concentrations in roots were significantly higher than in shoots. Scanning electron microscopy and X-ray microanalysis showed that metals were absorbed by internal root tissues. A hybrid wetland planted with T. domingensis may be implemented to improve not only metal but also chemical oxygen demand and total nitrogen removals.

Evolution of Anti-SARS-CoV-2 Therapeutic Antibodies.

Since the first COVID-19 reports back in December of 2019, this viral infection caused by SARS-CoV-2 has claimed millions of lives. To control the COVID-19 pandemic, the Food and Drug Administration (FDA) and/or European Agency of Medicines (EMA) have granted Emergency Use Authorization (EUA) to nine therapeutic antibodies. Nonetheless, the natural evolution of SARS-CoV-2 has generated numerous variants of concern (VOCs) that have challenged the efficacy of the EUA antibodies. Here, we review the most relevant characteristics of these therapeutic antibodies, including timeline of approval, neutralization profile against the VOCs, selection methods of their variable regions, somatic mutations, HCDR3 and LCDR3 features, isotype, Fc modifications used in the therapeutic format, and epitope recognized on the receptor-binding domain (RBD) of SARS-CoV-2. One of the conclusions of the review is that the EUA therapeutic antibodies that still retain efficacy against new VOCs bind an epitope formed by conserved residues that seem to be evolutionarily conserved as thus, critical for the RBD:hACE-2 interaction. The information reviewed here should help to design new and more efficacious antibodies to prevent and/or treat COVID-19, as well as other infectious diseases.

Aerial and underwater drones for marine litter monitoring in shallow coastal waters: factors influencing item detection and cost-efficiency.

Although marine litter monitoring has increased over the years, the pollution of coastal waters is still understudied and there is a need for spatial and temporal data. Aerial (UAV) and underwater (ROV) drones have demonstrated their potential as monitoring tools at coastal sites; however, suitable conditions for use and cost-efficiency of the methods still need attention. This study tested UAVs and ROVs for the monitoring of floating, submerged, and seafloor items using artificial plastic plates and assessed the influence of water conditions (water transparency, color, depth, bottom substrate), item characteristics (color and size), and method settings (flight/dive height) on detection accuracy. A cost-efficiency analysis suggests that both UAV and ROV methods lie within the same cost and efficiency category as current on-boat observation and scuba diving methods and shall be considered for further testing in real scenarios for official marine litter monitoring methods.

COVID-19-Related Aortic Thrombosis: A Report of Four Cases.

COVID-19 may predispose patients to an increased risk of thrombotic complications through various pathophysiological mechanisms. Most of the reports on a high incidence of thrombotic complications are in relation to deep vein thrombosis and pulmonary embolism, while the evidence about arterial thrombosis in patients with COVID-19 is limited. We describe 4 cases of aortic thrombosis and associated ischemic complications in patients with severe SARS-CoV-2 infection.

Towards medicine of excellence in Mexico: the "Código Infarto" protocol, a view from the perspective of translational bioethics.

INTRODUCTION: Mexico is the country with the highest mortality due to ST-elevation acute myocardial infarction (STEMI), and the IMSS has therefore developed the protocol of care for emergency departments called Código Infarto (Infarction Code). In this article, aspects of translational medicine are discussed with a bioethical and comprehensive perspective. OBJECTIVE: To analyze the Código Infarto protocol from the perspective of translational bioethics. METHOD: A problem-centered approach was carried out through reflective equilibrium (or Rawls' method), as well as by applying the integral method for ethical discernment. RESULTS: The protocol of care for emergency services Código Infarto is governed by evidence-based medicine and value-based medicine; it is guided by a principle of integrity that considers six dimensions of quality for the care of patients with STEMI. CONCLUSION: The protocol overcomes some adverse social determinants that affect STEMI medical care, reduces mortality and global economic disease burden, and develops medicine of excellence with high social reach.

INTRODUCCIÓN: México es el país con mayor mortalidad por infarto agudo de miocardio con elevación del segmento ST (IAM CEST), por lo que el Instituto Mexicano del Seguro Social desarrolló el protocolo de atención para los servicios de urgencias denominado Código Infarto. En este artículo se discuten aspectos de la medicina traslacional con una perspectiva bioética e integral. OBJETIVO: Analizar el protocolo Código Infarto desde la perspectiva de la bioética traslacional. MÉTODO: Se realizó una aproximación centrada en el problema a través del equilibrio reflexivo, así como la aplicación del método integral para el discernimiento ético. RESULTADOS: El protocolo de atención para los servicios de urgencias Código Infarto se rige por la medicina basada en la evidencia y la medicina basada en valores; se orienta por el principio de integridad que considera las seis dimensiones de la calidad para la atención de pacientes con IAM CEST. CONCLUSIÓN: El protocolo supera algunos determinantes sociales adversos que afectan la atención médica del IAM CEST, disminuye la mortalidad, la carga económica global de la enfermedad y desarrolla una medicina de excelencia de alto alcance social.

Interinstitutional clinical practice guidelines for the treatment of acute myocardial infarction.

INTRODUCTION: Mexico has the highest 30-day mortality due to acute myocardial infarction (AMI), which constitutes one of the main causes of mortality in the country: 28 % versus 7.5 % on average for the Organization for Economic Co-operation and Development member countries. OBJECTIVE: To establish critical pathways and essential interinstitutional pharmacological strategies for the care of patients with AMI in Mexico, regardless of their socioeconomic status. METHOD: A group of experts in AMI diagnosis and treatment, representatives of the main public health institutions in Mexico, as well as the Mexican cardiology societies, the Mexican Red Cross and representatives of the Spanish Society of Cardiology, were brought together in order to optimize strategies based on the best existing evidence. RESULTS: An interinstitutional clinical practice guideline was designed for early diagnosis and timely treatment of AMI with ST-segment elevation, following the clinical horizon of the disease, with the proposal of algorithms that improve the prognosis of patients who attend the emergency services due to an AMI. CONCLUSION: With these clinical practice guidelines, the group of experts proposes to universalize AMI diagnosis and treatment, regardless of patient socioeconomic status. INTRODUCCIÓN: México tiene la mortalidad más alta a 30 días por infarto agudo de miocardio (IAM), el cual constituye una de las principales causas de mortalidad en el país: 28 % versus 7.5 % del promedio de los países de la Organización para la Cooperación y el Desarrollo Económicos. OBJETIVO: Establecer las rutas críticas y las estrategias farmacológicas esenciales interinstitucionales para la atención de los pacientes con IAM en México, independientemente de su condición socioeconómica. MÉTODO: Se reunió a un grupo de expertos en diagnóstico y tratamiento de IAM, representantes de las principales instituciones públicas de salud de México, así como las sociedades cardiológicas mexicanas, Cruz Roja Mexicana y representantes de la Sociedad Española de Cardiología con la finalidad de optimizar las estrategias con base en la mejor evidencia existente. RESULTADOS: Se diseñó una guía de práctica clínica interinstitucional para el diagnóstico temprano y tratamiento oportuno del IAM con elevación del segmento ST, siguiendo el horizonte clínico de la enfermedad, con la propuesta de algoritmos que mejoren el pronóstico de los pacientes que acuden por IAM a los servicios de urgencias. CONCLUSIÓN: Con la presente guía práctica, el grupo de expertos propone universalizar el diagnóstico y tratamiento en el IAM, independientemente de la condición socioeconómica del paciente.

Polarised epithelial monolayers of the gastric mucosa reveal insights into mucosal homeostasis and defence against infection.

OBJECTIVE: Helicobacter pylori causes life-long colonisation of the gastric mucosa, leading to chronic inflammation with increased risk of gastric cancer. Research on the pathogenesis of this infection would strongly benefit from an authentic human in vitro model. DESIGN: Antrum-derived gastric glands from surgery specimens served to establish polarised epithelial monolayers via a transient air-liquid interface culture stage to study cross-talk with H. pylori and the adjacent stroma. RESULTS: The resulting 'mucosoid cultures', so named because they recapitulate key characteristics of the gastric mucosa, represent normal stem cell-driven cultures that can be passaged for months. These highly polarised columnar epithelial layers encompass the various gastric antral cell types and secrete mucus at the apical surface. By default, they differentiate towards a foveolar, MUC5AC-producing phenotype, whereas Wnt signalling stimulates proliferation of MUC6-producing cells and preserves stemness-reminiscent of the gland base. Stromal cells from the lamina propria secrete Wnt inhibitors, antagonising stem-cell niche signalling and inducing differentiation. On infection with H. pylori, a strong inflammatory response is induced preferentially in the undifferentiated basal cell phenotype. Infection of cultures for several weeks produces foci of viable bacteria and a persistent inflammatory condition, while the secreted mucus establishes a barrier that only few bacteria manage to overcome. CONCLUSION: Gastric mucosoid cultures faithfully reproduce the features of normal human gastric epithelium, enabling new approaches for investigating the interaction of H. pylori with the epithelial surface and the cross-talk with the basolateral stromal compartment. Our observations provide striking insights in the regulatory circuits of inflammation and defence.

First isolation of Leishmania infantum by blood culture in bovines from endemic area for canine visceral leishmaniasis.

Leishmaniasis is considered a parasitic disease that still causes serious consequences for mankind, because it presents a high mortality rate worldwide. Considered multi-hosts, the parasites of the genus Leishmania are able of infecting a wide variety of animal species. The dog was considered the main source of infection of visceral leishmaniasis (VL), in the urban area. However, the role of other animal species in the epidemiological cycle of the disease, such as cattle, remains unclear. Therefore, the aim of the present study was to evaluate the occurrence of Leishmania spp. in 100 bovines (Bos taurus) from an area endemic for canine VL, using blood culture and molecular analysis. By the sequencing analysis, one sample showed 100% similarity with Leishmania infantum. The results provide the first case of L. infantum isolation in one bovine from the periurban areas of Bauru, state of São Paulo, Brazil.

Validation of a Cell Proliferation Assay to Assess the Potency of a Dialyzable Leukocyte Extract Intended for Batch Release.

Transferon® is a blood product with immunomodulatory properties constituted by a complex mixture of peptides obtained from a human dialyzable leukocyte extract (DLE). Due to its complex nature, it is necessary to demonstrate batch consistency in its biological activity. Potency is the quantitative measure of biological activity and is also a quality attribute of drugs. Here we developed and validated a proliferation assay using Jurkat cells exposed to azathioprine, which is intended to determine the potency of Transferon® according to international guidelines for pharmaceuticals. The assay showed a linear response (2.5 to 40 µg/mL), coefficients of variation from 0.7 to 13.6% demonstrated that the method is precise, while r2 = 0.97 between the nominal and measured values obtained from dilutional linearity showed that the method is accurate. We also demonstrated that the cell proliferation response was specific for Transferon® and was not induced by its vehicle nor by other peptide complex mixtures (glatiramer acetate or hydrolyzed collagen). The bioassay validated here was used to assess the relative potency of eight released batches of Transferon® with respect to a reference standard, showing consistent results. The collective information from the validation and the assessment of several batches indicate that the bioassay is suitable for the release of Transferon®.

[Efecto de la rehabilitación cardiaca temprana en pacientes incluidos en Código Infarto].

Introduction: Early cardiac rehabilitation (ECR) implemented in the Infarction Code (IC) protocol is a strategy in the care of acute myocardial infarction. The purpose of this study was to identify the effect of ECR in IC-included patients. Method: Case-control study. Consecutive patients diagnosed with acute myocardial infarction and admitted to a cardiology hospital between February 2015 and June 2017 were included. Two groups were created: I and II, before and after IC and ECR. Results: We included 1141 patients, 220 in group I and 921 in group II, with an age of 62.64 ± 10.53 years; 80.9 % were males and 19.1 % females. The main risk factors for groups I and II were sedentariness, 92.7 % versus 77.8 %; dyslipidemia, 80.9 % versus 55.8 %; hypertension, 63.2 % versus 62 %; smoking, 66.8 % versus 59.2 %; and diabetes, 54.5 % versus 59.1 %. Rehabilitation was started earlier (1.8 ± 1.6 versus 4.2 ± 3.2) and the days spent in intensive therapy and hospitalization were fewer in group II (2.4 ± 2.2 versus 4.8 ± 4.1 and 8.6 ± 5.2 versus 12.3 ± 7.7, p < 0.0001, respectively), as well as the days of disability (58.6 versus 67.7). Conclusions: IC and ECR are complementary strategies that allow an early discharge from intensive therapy and hospitalization, as well as better quality of life and fewer days of disability leave.

Introducción: La rehabilitación cardiaca temprana (RCT) implementada en el protocolo Código Infarto (CI) es una estrategia en la atención del infarto agudo de miocardio. El objetivo fue identificar el efecto de la RCT en pacientes incluidos en CI. Método: Estudio de casos y controles. Se incluyeron pacientes consecutivos con diagnóstico de infarto agudo de miocardio ingresados a un hospital de cardiología entre febrero de 2015 y junio de 2017. Se crearon dos grupos: I y II, antes y después de CI y RCT. Resultados: Se incluyeron 1141 pacientes: 220 del grupo I y 921 del grupo II, edad 62.64 ± 10.53 años; 80.9 % hombres y 19.1 % mujeres. Los principales factores de riesgo para los grupos I y II fueron sedentarismo, 92.7 y 77.8 %; dislipidemia, 80.9 y 55.8 %; hipertensión, 63.2 y 62 %; tabaquismo, 66.8 y 59.2 %; y diabetes, 54.5 y 59.1 %. En el grupo II se inició antes la rehabilitación (1.8 ± 1.6 y 4.2 ± 3.2) y los días en terapia intensiva y hospitalización fueron menores (2.4 ± 2.2 y 4.8 ± 4.1; 8.6 ± 5.2 y 12.3 ± 7.7), así como los días de incapacidad (58.6 y 67.7). Conclusiones: CI y RCT son estrategias complementarias que permiten alta temprana de terapia intensiva y hospitalización, mejor calidad de vida y menos días de incapacidad laboral.

The norpurpureine alkaloid from Annona purpurea inhibits human platelet activation in vitro.

BACKGROUND: The leaves of Annona purpurea have yielded several alkaloids with anti-aggregation activities against rabbit platelets. This is promising in the search for agents that might act against platelets and reduce the incidence of cardiovascular diseases. Since significant differences in platelet function have been reported between human and animal platelets, a study focusing on the effect of A. purpurea extracts against human platelet activation is necessary. METHODS: The compounds in an A. purpurea ethanolic extract underwent bio-guided fractionation and were used for in vitro human platelet aggregation assays to isolate the compounds with anti-platelet activity. The bioactive compounds were identified by spectroscopic analysis. Additional platelet studies were performed to characterize their action as inhibitors of human platelet activation. RESULTS: The benzylisoquinoline alkaloid norpurpureine was identified as the major anti-platelet compound. The IC50 for norpurpureine was 80 µM against platelets when stimulated with adenosine 5'-diphosphate (ADP), collagen and thrombin. It was pharmacologically effective from 20 to 220 µM. Norpurpureine (220 µM) exhibited its in vitro effectiveness in samples from 30 healthy human donors who did not take any drugs during the 2 weeks prior to the collection. Norpurpureine also gradually inhibited granule secretion and adhesion of activated platelets to immobilized fibrinogen. At the intra-platelet level, norpurpureine prevented agonist-stimulated calcium mobilization and cAMP reduction. Structure-activity relationship analysis indicates that the lack of a methyl group at the nitrogen seems to be key in the ability of the compound to interact with its molecular target. CONCLUSION: Norpurpureine displays a promising in vitro pharmacological profile as an inhibitor of human platelet activation. Its molecular target could be a common effector between Ca2+ and cAMP signaling, such as the PLC-PKC-Ca2+ pathway and PDEs. This needs further evaluation at the protein isoform level.

Influence of Language and Culture in the Primary Care of Spanish-Speaking Latino Adults with Poorly Controlled Diabetes: A Qualitative Study.

Background: We examined the role of language and culture in the interactions between Spanish-speaking Latino patients with poorly controlled diabetes - a fast-growing population in the United States - and their primary care providers. Methods: We conducted four focus groups with 36 non-US born Spanish-speaking patients with elevated HbA1c. Participants were insured health plan members with either English-speaking (2 groups) or Spanish-speaking (2 groups) primary care providers. Moderated discussions focused on visit preparation, communication during visit, and role of other care team members. Key themes derived from these discussions were then linked to corresponding Latino cultural constructs. Results: Patients had a mean age of 57.9 (±11.2) years and last measured HbA1c was 8.6% (1.5%). Two communication-related themes (reluctance to switch providers and use of intermediaries) and two visit-related themes (provider-driven visit agendas and problem-based visits) emerged from our analyses. These themes reflected the cultural constructs of confianza (trust), familismo (family), respeto (deference), and simpatía (harmonious relationship). Trust in the patient-provider relationship led many participants to remain with English-speaking providers who treated them well. Patients with either language concordant and discordant providers reported reliance on family or other intermediaries to close communication gaps. Deference to physician expertise and authority led to visit expectations that it is the doctor's job to know what to ask and that visits were intended to address specific, often symptom-driven problems. Conclusions: Spanish-speaking Latino patients' cultural expectations play an important role in framing their primary care interactions. Recognizing culturally influenced visit expectations is an important step toward improving patient-provider communication.

Impact of the implementation of the Infarction Code strategy in patients with acute myocardial infarction diagnosis in the Hospital de Cardiología of the Centro Médico Nacional Siglo XXI / Impacto de la implementación de Código Infarto en pacientes con infarto agudo de miocardio con elevación del segmento ST en el Hospital de Cardiología del Centro Médico Nacional Siglo XXI.

Objective: To evaluate the impact of the implementation of the Infarction Code strategy in patients with acute myocardial infarction diagnosis. Methods: Consecutive patients with ST-elevation acute myocardial infarction ≤12 hours of evolution, were included in the infarction code strategy, before (Group I) and after (Group II). Times of medical attention and major cardiovascular events during hospitalization were analyzed. Results: 1227 patients were included, 919 men (75%) and 308 women (25%) with an average age of 62 ± 11 years. Among Group I and Group II, percutaneous coronary intervention reperfusion therapy changed (16.6% to 42.6%), fibrinolytic therapy (39.3% to 25%), and patients who did not receive any form of reperfusion therapy (44% to 32.6%; p < 0.0001). Times of medical attention decreased significantly (door-to-needle time decreased from 92 to 72 minutes, p = 0.004; door-to-balloon time decreased from 140 to 92 minutes, p < 0.0001). Kidney failure (24.6% vs. 17.9%; p = 0.006), major complications (35.3% to 29.3%), and death (21% vs. 12%; odds ratio: 0.52; 95% confidence interval: 0.38-0.71; p = 0.004). also decreased. Conclusion: The Infarction Code strategy improved treatment, times of medical attention and decreased complications and death in these patients.

Obesity and Functioning Among Individuals with Chronic Obstructive Pulmonary Disease (COPD).

In COPD, body composition studies have focused primarily on low BMI. We examined obesity (BMI ≥ 30 kg/m(2)) as a risk factor for poor function and longitudinal functional decline. Data from a longitudinal cohort of adults with COPD (n = 1096) and an age- and sex-matched comparison group collected in two in-person visits ∼49 months apart were analyzed. Two measures of functioning were examined: six-minute walk distance (6MWD) and Short Physical Performance Battery (SPPB). Multivariate regression analyses examined relationships of obesity with functioning. Secondary analyses stratified by GOLD classification (GOLD-0/1, GOLD-2, GOLD-3/4). Obesity (53% of COPD cohort) was associated cross-sectionally with 6MWD and SPPB in COPD, and only with 6MWD in the comparison group. Obesity predicted significant functional decline in 6MWD for individuals with COPD (odds ratio (OR) for decline [95% CI] 1.8 [1.1, 2.9]), but not the comparison group. Secondary analyses revealed that the risk of decline was significant only in those with more severe COPD (GOLD 3/4, OR = 2.3 [1.0, 5.4]). Obesity was highly prevalent and was associated with poor function concurrently and with subsequent decline in 6MWD in COPD. Obesity in COPD should be considered a risk not only for more co-morbidities and greater health care use, but also for functional decline.

A bivalent typhoid live vector vaccine expressing both chromosome- and plasmid-encoded Yersinia pestis antigens fully protects against murine lethal pulmonary plague infection.

Live attenuated bacteria hold great promise as multivalent mucosal vaccines against a variety of pathogens. A major challenge of this approach has been the successful delivery of sufficient amounts of vaccine antigens to adequately prime the immune system without overattenuating the live vaccine. Here we used a live attenuated Salmonella enterica serovar Typhi strain to create a bivalent mucosal plague vaccine that produces both the protective F1 capsular antigen of Yersinia pestis and the LcrV protein required for secretion of virulence effector proteins. To reduce the metabolic burden associated with the coexpression of F1 and LcrV within the live vector, we balanced expression of both antigens by combining plasmid-based expression of F1 with chromosomal expression of LcrV from three independent loci. The immunogenicity and protective efficacy of this novel vaccine were assessed in mice by using a heterologous prime-boost immunization strategy and compared to those of a conventional strain in which F1 and LcrV were expressed from a single low-copy-number plasmid. The serum antibody responses to lipopolysaccharide (LPS) induced by the optimized bivalent vaccine were indistinguishable from those elicited by the parent strain, suggesting an adequate immunogenic capacity maintained through preservation of bacterial fitness; in contrast, LPS titers were 10-fold lower in mice immunized with the conventional vaccine strain. Importantly, mice receiving the optimized bivalent vaccine were fully protected against lethal pulmonary challenge. These results demonstrate the feasibility of distributing foreign antigen expression across both chromosomal and plasmid locations within a single vaccine organism for induction of protective immunity.