Nontuberculous mycobacterial infections in patients with hematologic malignancies and recipients of hematopoietic stem cell transplantation.

BACKGROUND: The incidence of mycobacterial infections in patients with hematologic malignancies and hematopoietic stem cell transplant (HSCT) recipients is increasing, contributing to significant mortality and morbidity. This review explores the epidemiology, risk factors, clinical presentation, diagnosis, and treatment of nontuberculous mycobacteria (NTM) in this population. METHODS: A literature search was performed using PubMed with keywords and MeSH terms pertaining to the topics of nontuberculous mycobacteria, hematologic malignancies, hematopoietic stem cell transplant, cellular therapies, chimeric antigen therapies, epidemiology, diagnosis, and treatment. Additionally, we examined the reference lists of the included articles to identify other pertinent studies. RESULTS: Diagnosing mycobacterial disease among patients with hematologic disease and treatment-associated immunosuppressive conditions is challenging due to the lack of distinctive clinical, radiographic, and laboratory markers, as well as the atypical manifestations compared to immunocompetent patients. Treatment involves using a combination of antibiotics for extended durations, coupled with strategies to achieve source control and reduce immunosuppression when feasible. This is complicated by the absence of clear data correlating in-vitro drug susceptibility and clinical outcome for many antimicrobials use to treat NTM, adverse drug-drug interactions, and the frequent challenges related to poor medication tolerability and toxicities. CONCLUSION: The rising incidence and corresponding clinical challenges of mycobacterial infections in this unique patient population necessitate a heightened awareness and familiarity of NTM disease by clinicians to achieve timely diagnosis and favorable treatment outcomes.

Immunomodulators for severe coronavirus disease-2019 in transplant patients: Do they increase the risk of secondary infection?

BACKGROUND: Current guidelines recommend immunomodulators, tocilizumab or baricitinib, for the management of severe coronavirus disease-2019 (COVID-19) in patients with increasing oxygen requirements. Given their immunosuppressive effects, there is a concern for higher rates of infection among transplant recipients. METHODS: A retrospective cohort study of transplant patients with severe COVID-19 between April 2020 and January 2022 was performed at the Mayo Clinic. The primary outcome was incidence of secondary infections after COVID-19 diagnosis. Secondary outcomes were 90-day mortality, ventilatory days, and thromboembolic events. RESULTS: A total of 191 hospitalized transplant patients were studied, including 77 (40.3%) patients who received an immunomodulator. Overall, 89% were solid organ transplant recipients, with kidney as the most common transplanted organ (50.3%). The majority (89.0%) required oxygen supplementation on admission, and 39.8% of these patients required mechanical ventilation during the hospital course. There was no significant difference in the incidence of secondary infections between those who received or did not receive an immunomodulator (p = .984). Likewise, there was no difference in 90-day mortality between patients who received or did not receive an immunomodulator (p = .134). However, higher mortality was observed among patients that developed a secondary infection (p < .001). CONCLUSION: The use of immunomodulators in transplant patients with severe COVID-19 was not significantly associated with an increased risk of secondary infections. Secondary infections were associated with higher risk of all-cause mortality. Future studies of larger cohorts are needed to explore the effect of immunomodulators on survival among transplant patients with COVID-19.

Difference between SARS-CoV-2, seasonal coronavirus, influenza, and respiratory syncytial virus infection in solid organ transplant recipients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been raging since the end of 2019 and has shown worse outcomes in solid organ transplant (SOT) recipients. The clinical differences as well as outcomes between respiratory viruses have not been well defined in this population. METHODS: This is a retrospective cohort study of adult SOT recipients with nasopharyngeal swab or bronchoalveolar lavage PCR positive for either SARS-CoV-2, seasonal coronavirus, respiratory syncytial virus (RSV) or influenza virus from January 2017 to October 2020. The follow up period was 3 months. Clinical characteristics and outcomes were evaluated. RESULTS: A total of 377 recipients including 157 SARS-CoV-2, 70 seasonal coronavirus, 50 RSV and 100 influenza infections were identified. The most common transplanted organ was kidney 224/377 (59.4%). Lower respiratory tract infection (LRTI) was found in 210/377 (55.7%) and the risk factors identified with multivariable analysis were SARS-CoV-2 infection, steroid use, and older age. Co- and secondary infections were seen in 77/377 (20.4%) recipients with bacterial pathogens as dominant. Hospital admission was seen in 266/377 (67.7%) recipients without significant statistical difference among viruses, however, ICU admission, mechanical ventilation and mortality were higher with SARS-CoV-2 infection. In the multivariable model, the risk factors for mortality were SARS-CoV-2 infection and older age. CONCLUSIONS: We found higher incidence of ICU admission, mechanical ventilation, and mortality among SARS-CoV-2 infected recipients. Older age was found to be the risk factor for lower respiratory tract infection and mortality for SARS-CoV-2, coronaviruses, RSV and influenza virus groups.

Clinical and microbiologic outcomes of central nervous system cryptococcosis: Re-examining the need for a 2-week cerebrospinal fluid analysis.

BACKGROUND: Cryptococcus spp. infection involving the central nervous system (CNS) is associated with poor outcomes. Current guidelines recommend repeating a cerebrospinal fluid (CSF) fungal culture after 2 weeks of treatment to evaluate for clearance. However, this practice has not clearly been associated with outcomes. OBJECTIVES: We sought to assess the relationship between CSF fungal clearance at 2 weeks and 12-month mortality in patients with CNS cryptococcosis. METHODS: This is a retrospective cohort study from 2011 to 2020 of patients with CNS cryptococcosis. Factors associated with 12-month mortality were assessed with Fisher's exact test for categorical variables and Mann-Whitney test for continuous variables. RESULTS: Among 51 patients with CNS cryptococcosis, 42 (82.4%) were initially CSF culture positive. Among 27 patients with follow-up CSF culture at 2 weeks, 6 (22.2%) had a positive result. Factors associated with a positive CSF culture at 2 weeks were an initial CSF cryptococcal antigen titre ≥1:2560, fungaemia, and an elevated intracranial pressure requiring therapeutic lumbar punctures. The 12-month mortality rate was 33.3%, and this was significantly associated with baseline fungaemia, extra-CNS cryptococcal involvement and requirement of intensive care unit level of care. Lack of CSF culture clearance by 2 weeks was not associated with 12-month mortality. CONCLUSIONS: CNS cryptococcosis has a high mortality rate. A markedly elevated CSF cryptococcal antigen, and opening CSF pressure was associated with lack of CSF culture clearance at 2 weeks of treatment. Severe disseminated disease and cryptococcemia were associated with 12-month mortality.

Clinical presentation and outcomes of COVID-19 following hematopoietic cell transplantation and cellular therapy.

BACKGROUND: One year into the pandemic, published data on hematopoietic cell transplantation (HCT) recipients with coronavirus disease 2019 (COVID-19) remain limited. METHODS: Single-center retrospective cohort study of adult HCT recipients with polymerase chain reaction (PCR)-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. RESULTS: Twenty-eight consecutive transplantation and cellular therapy patients (autologous, n = 12; allogeneic, n = 15; chimeric antigen receptor T-cell therapy [CAR-T], n = 1) with COVID-19 were identified. The median age was 57 years. The median time from HCT to COVID-19 diagnosis was 656 days (interquartile range [IQR], 33-1274). Patients were followed for a median of 59 days (IQR, 40-88). Among assessable patients (n = 19), 10 (53%) had documented virological clearance; median time to clearance was 34 days (range, 21-56). Out of 28, 12 (43%), 6 (21%), and 10 (36%) patients had mild, moderate, and severe/critical disease, respectively. Overall mortality was 25%, nearly identical for autologous and allogeneic HCT, and exclusively seen in hospitalized patients, older than 50 years of age with severe COVID-19. None of the patients with mild (n = 12) or moderate (n = 6) COVID-19 died whereas 7/10 patients (70%) with severe/critical COVID-19 died (P = .0001). Patients diagnosed with COVID-19 within 12 months of HCT exhibited higher mortality (57% vs 14%; P = .04). All-cause 30-day mortality (n = 4) was 14%. A higher proportion of patients who died within 30 days of COVID-19 diagnosis (3/4) were receiving ≥2 immunosuppressants, compared with patients who survived beyond 30 days after COVID-19 diagnosis (2/24; 75% vs. 8%; P = .01). CONCLUSIONS: Mortality in COVID-19 HCT patients is higher than that of the age-comparable general population and largely dependent on age, disease severity, timing from HCT, and intensity of immunosuppression.

Successful Treatment of Invasive Fungal Infection Due to Highly Resistant Aspergillus calidoustus in an Allogeneic Hematopoietic Cell Transplant Recipient.

Invasive aspergillosis (IA) is the most common invasive fungal infection following a hematopoietic cell transplant, with emerging cryptic species exhibiting resistance to commonly used antifungals such as azoles. These species have been increasingly found after the introduction of anti-mold prophylaxis. We report a case of a 56-year-old female with primary myelofibrosis whose allogeneic hematopoietic cell transplant was complicated by disseminated fungal infection (skin, lung) due to Aspergillus calidoustus, a cryptic specie. Treatment of Aspergillus species remains challenging as these cryptic species are usually resistant to azoles including voriconazole which is the first line of treatment of IA. Infection was successfully treated with surgical excision and combination antifungal therapy based on in vitro susceptibility and synergy testing. Therapy included isavuconazole, a drug that has been shown to be non-inferior to voriconazole in the treatment of invasive mold infections.

Clinical Characteristics and Outcomes of Clostridioides difficile Infection in Patients With Left Ventricular Assist Device.

The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010-2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5-647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87-17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18-5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI.

Effect of Rifabutin in Dolutegravir Dosing: A Case Series.

Background: Tuberculosis (TB) is the leading cause of death in human immunodeficiency virus (HIV)-infected people worldwide. Currently there are no studies examining the use of Rifabutin (RBN) and Dolutegravir (DTG) in co-infected persons. This is a case series of 4 co-infected patients receiving both agents who underwent Pharmacokinetic (PK) analysis. Methods and Results: This is a retrospective chart review study of four patients diagnosed with both HIV and TB, receiving RBN and DTG and undergoing therapeutic drug monitoring. All 4 cases had lower than expected DTG concentrations at least once, including those on the current recommended dose of DTG with RBN, and even those receiving higher doses. Conclusions: Given the frequency of low DTG and RBN concentrations, therapeutic drug monitoring (TDM) for these drugs is advisable. Prospective clinical studies are needed to further determine the PK interactions between RBN and DTG, and virologic response to treatment.

Gender differences in cardiology professionals: A Latin American Survey.

BACKGROUND: Gender-based differences among cardiology professionals have been reported in North America and Europe. However, the perspective of Latin American cardiologists remains unexplored. OBJECTIVES: The objectives of the study were to analyze the gender gap perspective among cardiologists from Latin America. METHODS: A cross-sectional study using an online survey directed to Latin American cardiologists from five different cardiology societies. The survey included questions on demographic data, professional development in the field of cardiology, and perceived barriers in clinical practice. RESULTS: A total of 240 professionals were surveyed, of which 41.7% were women (100) and 58.3% were men (140). The majority of women tend to work in the subfields of clinical cardiology and cardiovascular imaging. Women were underrepresented as heads of departments, earn less, and report less work satisfaction than men. The barriers that female cardiologists face at their workplace include labor discrimination, sexual harassment, family-related concerns, and lack of career development. CONCLUSIONS: The survey points toward the prevalence of a gender gap among cardiologists in Latin America, which is primarily driven by labor discrimination, sexual harassment, family-related concerns, and lack of career development among female cardiologists. Actions aimed at addressing this issue should be considered by different parties.

ANTECEDENTES: Existen diferencias de género entre los profesionales en cardiología en Europa y Norteamérica. La perspectiva de este suceso en América Latina permanece inexplorado. OBJECTIVOS: Analizar la perspectiva de la diferencia de género entre cardiólogos en América Latina. METODOS: Estudio transversal en el que se usó un cuestionario en línea dirigido a profesionales en cardiología en América Latina. El cuestionario incluía datos demográficos, desarrollo profesional en el campo de la campo de la cardiología y la percepción de las barreras en la práctica clínica. RESULTADOS: un total de 240 profesionales fueron analizados, de los cuales 41.7% (100) fueron mujeres y 58.3% (140) fueron hombres. La mayoría de las mujeres suelen trabajar en el área de imagen cardiovascular. Se encontró subrepresentación del género femenino en jefaturas de departamento, tienen un menor salario y reportan menor satisfacción laboral en comparación con los hombres. Las barreas que enfrentan en su lugar de trabajo fueron discriminación laboral, acoso sexual y falta de desarrollo profesional. CONCLUSIONES: El cuestionario señala la prevalencia de la diferencia de género en América Latina, principalmente por discriminación laboral, acoso sexual y falta de desarrollo profesional. Se necesita tomar acciones interinstitucionales que vayan dirigidas a reducir y eliminar esta brecha.

COVID-19 in solid organ transplant recipients: A systematic review and meta-analysis of current literature.

Severe acute respiratory virus syndrome 2 (SARS-CoV-2) has led to a worldwide pandemic. Early studies in solid organ transplant (SOT) recipients suggested a wide variety of presentations, however, there remains a paucity of robust data in this population. We conducted a systematic review and meta-analysis of SOT recipients with SARS-CoV-2 infection from January 1st t October 9th, 2020. Pooled incidence of symptoms, treatments and outcomes were assessed. Two hundred and fifteen studies were included for systematic review and 60 for meta-analysis. We identified 2,772 unique SOT recipients including 1,500 kidney, 505 liver, 141 heart and 97 lung. Most common presenting symptoms were fever and cough in 70.2% and 63.8% respectively. Majority (81%) required hospital admission. Immunosuppressive medications, especially antimetabolites, were decreased in 76.2%. Hydroxychloroquine and interleukin six antagonists were administered in59.5% and 14.9% respectively, while only few patients received remdesivir and convalescent plasma. Intensive care unit admission was 29% from amongst hospitalized patients. Only few studies reported secondary infections. Overall mortality was 18.6%. Our analysis shows a high incidence of hospital admission in SOT recipients with SARS-CoV-2 infection. As management of SARS-CoV-2 continues to evolve, long-term outcomes among SOT recipients should be assessed in future studies.

Evaluation of pharmacoinvasive strategy versus percutaneous coronary intervention in patients with acute myocardial infarction with ST-segment elevation at the National Institute of Cardiology (PHASE-MX).

Objective: The objective of PHASE-MX registry is to validate the efficacy and safety of the pharmacoinvasive strategy in comparison with percutaneous coronary intervention (PCI) in patients with acute myocardial infarction with ST segment elevation (STEMI) in a metropolitan region of Mexico. The primary outcome will consist of the composite of cardiovascular death, re-infarction, stroke and cardiogenic shock. Methods: The PHASE-MX registry will include a prospective cohort of patients with STEMI who received reperfusion treatment (mechanical of pharmacological) in the first 12 h after the onset of symptoms. The registry is designed to compare the efficacy and safety of primary PCI and pharmacoinvasive strategy. The simple size was calculated in 344 patients divided into two groups, with an estimated loss rate of 10%. Patients included in the PHASE-MX cohort will be followed for up to one year. Conclusion: In Mexico, only 5 out of 10 patients with STEMI have access to reperfusion therapy. Pharmacoinvasive strategy is takes advantage of the accessibility of fibrinolysis and the effectiveness of PCI. The present research protocol aims to provide information that serves as a link between information derived from controlled clinical trials and records derived from real world experience.

Objetivo: El objetivo del registro PHASE-MX es validar la eficacia y seguridad de la estrategia farmacoinvasiva en comparación con la angioplastia coronaria transluminal percutánea primaria (ACTPp) en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en una región metropolitana de México. El desenlace primario es el compuesto de muerte cardiovascular, reinfarto, accidente vascular cerebral y choque cardiogénico. Métodos: El registro PHASE-MX es una cohorte prospectiva de pacientes con IAMCEST que recibieron tratamiento de reperfusión (mecánico o farmacológico) en las primeras 12 horas desde el inicio de los síntomas, atendidos en el Instituto Nacional de Cardiología Ignacio Chávez. El análisis estadístico se basa en la no inferioridad de la estrategia farmacoinvasiva en comparación con la ACTPp. Se calcula un tamaño de muestra de 344 pacientes divididos en dos grupos (angioplastia primaria y estrategia farmacoinvasiva), considerada una tasa de pérdidas de 10%. Los pacientes incluidos en la cohorte PHASE-MX se seguirán durante un año. Discusión: En México, sólo 5 de cada 10 pacientes con IAMCEST tienen acceso al tratamiento de reperfusión. La estrategia farmacoinvasiva aprovecha la accesibilidad de la fibrinólisis y la efectividad de la ACTPp, por lo que podría resultar el método de elección en el tratamiento del IAMCEST en la mayoría de los casos. El presente protocolo de investigación pretende aportar información que sirva como enlace entre la información derivada de los estudios clínicos controlados y los registros derivados de la experiencia del mundo real.

Evaluation of pharmacoinvasive strategy versus percutaneous coronary intervention in patients with acute myocardial infarction with ST segment elevation at the National Institute of Cardiology (PHASE-MX).

Objective: The objective of PHASE-MX registry is to validate the efficacy and safety of the pharmacoinvasive strategy in comparison with percutaneous coronary intervention (PCI) in patients with acute myocardial infarction with ST segment elevation (STEMI) in a metropolitan region of Mexico. The primary outcome will consist of the composite of cardiovascular death, re-infarction, stroke and cardiogenic shock. Methods: The PHASE-MX registry will include a prospective cohort of patients with STEMI who received reperfusion treatment (mechanical of pharmacological) in the first 12 h after the onset of symptoms. The registry is designed to compare the efficacy and safety of primary PCI and pharmacoinvasive strategy. The simple size was calculated in 344 patients divided into two groups, with an estimated loss rate of 10%. Patients included in the PHASE-MX cohort will be followed for up to one year. Conclusion: In Mexico, only 5 out of 10 patients with STEMI have access to reperfusion therapy. Pharmacoinvasive strategy is takes advantage of the accessibility of fibrinolysis and the effectiveness of PCI. The present research protocol aims to provide information that serves as a link between information derived from controlled clinical trials and records derived from real world experience.

Objetivo: El objetivo del registro PHASE-MX es validar la eficacia y seguridad de la estrategia farmacoinvasiva en comparación con la angioplastia coronaria transluminal percutánea primaria (ACTPp) en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en una región metropolitana de México. El desenlace primario es el compuesto de muerte cardiovascular, reinfarto, accidente vascular cerebral y choque cardiogénico. Métodos: El registro PHASE-MX es una cohorte prospectiva de pacientes con IAMCEST que recibieron tratamiento de reperfusión (mecánico o farmacológico) en las primeras 12 horas desde el inicio de los síntomas, atendidos en el Instituto Nacional de Cardiología Ignacio Chávez. El análisis estadístico se basa en la no inferioridad de la estrategia farmacoinvasiva en comparación con la ACTPp. Se calcula un tamaño de muestra de 344 pacientes divididos en dos grupos (angioplastia primaria y estrategia farmacoinvasiva), considerada una tasa de pérdidas de 10%. Los pacientes incluidos en la cohorte PHASE-MX se seguirán durante un año. Discusión: En México, sólo 5 de cada 10 pacientes con IAMCEST tienen acceso al tratamiento de reperfusión. La estrategia farmacoinvasiva aprovecha la accesibilidad de la fibrinólisis y la efectividad de la ACTPp, por lo que podría resultar el método de elección en el tratamiento del IAMCEST en la mayoría de los casos. El presente protocolo de investigación pretende aportar información que sirva como enlace entre la información derivada de los estudios clínicos controlados y los registros derivados de la experiencia del mundo real.

Genetic individualization of Cannabis sativa by a short tandem repeat multiplex system.

Cannabis sativa is the most frequently used of all illicit drugs in the USA. Cannabis has been used throughout history for its stems in the production of hemp fiber, seed for oil and food, and buds and leaves as a psychoactive drug. Short tandem repeats (STRs) were chosen as molecular markers owing to their distinct advantages over other genetic methods. STRs are codominant, can be standardized such that reproducibility between laboratories can be easily achieved, have a high discrimination power, and can be multiplexed. In this study, six STR markers previously described for C. sativa were multiplexed into one reaction. The multiplex reaction was able to individualize 98 cannabis samples (14 hemp and 84 marijuana, authenticated as originating from 33 of the 50 states of the USA) and detect 29 alleles averaging 4.8 alleles per loci. The data did not relate the samples from the same state to each other. This is the first study to report a single-reaction sixplex and apply it to the analysis of almost 100 cannabis samples of known geographic origin.

Promoting synergistic partnerships in low resource countries: a case study exemplar.

OBJECTIVES/AIMS: The purpose of this discussion is to explore the dynamics of partnership and its impact on both nursing faculty at Hue University of Medicine and Pharmacy (HueUMP) and Health Volunteers Overseas (HVO) volunteers. DESIGN: A case study approach was used to promote understanding of partnerships in global health. DISCUSSION: Collaboration between HueUMP's nursing program and HVO is one of the most dynamic HVO nurse educator programs with five volunteer visits to Vietnam within a two-year period. Volunteer efforts include workshops to meet the diverse needs and interests of nursng faculty. We also emphasize the potential for ongoing strategic program planning integrating components from other nursing partnerships in the Southeast Asian region. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: If we are to continue meeting partnership goals, we must recognize that partnerships should evolve according to the goals of HueUMP nursing faculty and the context of nursing in Vietnam.

Comparison of extracorporeal shock wave therapy with botulinum toxin type A in the treatment of plantar fasciitis.

OBJECTIVE: To compare the efficacy of extracorporeal shock wave therapy (ESWT) with botulinum toxin type A (BoNT-A) in the treatment of plantar fasciitis (PF). DESIGN: Open label, prospective, randomized study. RESULTS: A total of 72 patients were included. In all participants the median (and interquartile range) of the visual analog scale (VAS) of pain result, when taking the first steps, was 8 (6-9) points before treatment and 6 (4-8) points after treatment (p < 0.001). In the group of patients that received ESWT, the median (and interquartile range) of improvement in the VAS of pain result, when taking the first steps, was 2 (1-4) points, and in the group of patients that received BoNT-A the same result was 1 (0-2) points (p = 0.009). In the group of patients that received ESWT, the median (and interquartile range) of improvement in the Roles and Maudsley scale of pain result was 1 (0-1) points, and in the group of patients that received BoNT-A the same result was 0 (0-1) points (p = 0.006). In a multivariate analysis use of ESWT and lower weight were associated with improvement of pain with treatment in at least one of the three VAS of pain scales used in the study. CONCLUSION: ESWT was superior to BoNT-A in the control of pain in patients with PF. Implications for Rehabilitation Plantar fasciitis is characterized by pain at the calcaneal origin of the plantar fascia, exacerbated by weight bearing after prolonged periods of rest. Although studies comparing extracorporeal shock wave therapy or botulinum toxin type A to placebo suggest a superiority of the first one, no reliable data exist about it. Extracorporeal shock wave therapy was superior to botulinum toxin type A in the control of pain in patients with PF.

Evaluation of pharmacoinvasive strategy versus percutaneous coronary intervention in patients with acute myocardial infarction with ST-segment elevation at the National Institute of Cardiology (PHASE-MX) / Evaluación de la estrategia farmacoinvasiva versus angioplastia coronaria transluminal percutánea primaria en pacientes con infarto agudo de miocardio con elevación del segmento ST en el Instituto Nacional de Cardiología (PHASE-MX)

Abstract Objective: The objective of PHASE-MX registry is to validate the efficacy and safety of the pharmacoinvasive strategy in comparison with percutaneous coronary intervention (PCI) in patients with acute myocardial infarction with ST segment elevation (STEMI) in a metropolitan region of Mexico. The primary outcome will consist of the composite of cardiovascular death, re-infarction, stroke and cardiogenic shock. Methods: The PHASE-MX registry will include a prospective cohort of patients with STEMI who received reperfusion treatment (mechanical of pharmacological) in the first 12 h after the onset of symptoms. The registry is designed to compare the efficacy and safety of primary PCI and pharmacoinvasive strategy. The simple size was calculated in 344 patients divided into two groups, with an estimated loss rate of 10%. Patients included in the PHASE-MX cohort will be followed for up to one year. Conclusion: In Mexico, only 5 out of 10 patients with STEMI have access to reperfusion therapy. Pharmacoinvasive strategy is takes advantage of the accessibility of fibrinolysis and the effectiveness of PCI. The present research protocol aims to provide information that serves as a link between information derived from controlled clinical trials and records derived from real world experience.

Resumen Objetivo: El objetivo del registro PHASE-MX es validar la eficacia y seguridad de la estrategia farmacoinvasiva en comparación con la angioplastia coronaria transluminal percutánea primaria (ACTPp) en pacientes con infarto agudo de miocardio con elevación del segmento ST (IAMCEST) en una región metropolitana de México. El desenlace primario es el compuesto de muerte cardiovascular, reinfarto, accidente vascular cerebral y choque cardiogénico. Métodos: El registro PHASE-MX es una cohorte prospectiva de pacientes con IAMCEST que recibieron tratamiento de reperfusión (mecánico o farmacológico) en las primeras 12 horas desde el inicio de los síntomas, atendidos en el Instituto Nacional de Cardiología Ignacio Chávez. El análisis estadístico se basa en la no inferioridad de la estrategia farmacoinvasiva en comparación con la ACTPp. Se calcula un tamaño de muestra de 344 pacientes divididos en dos grupos (angioplastia primaria y estrategia farmacoinvasiva), considerada una tasa de pérdidas de 10%. Los pacientes incluidos en la cohorte PHASE-MX se seguirán durante un año. Discusión: En México, sólo 5 de cada 10 pacientes con IAMCEST tienen acceso al tratamiento de reperfusión. La estrategia farmacoinvasiva aprovecha la accesibilidad de la fibrinólisis y la efectividad de la ACTPp, por lo que podría resultar el método de elección en el tratamiento del IAMCEST en la mayoría de los casos. El presente protocolo de investigación pretende aportar información que sirva como enlace entre la información derivada de los estudios clínicos controlados y los registros derivados de la experiencia del mundo real.

Valoración del Estrés en Toros Brasileros y Venezolanos Mediante la Evaluación de las Concentraciones de Cortisol y el Recuento Leucocitario / Assessment of stress in Brazilian and Venezuelan Bulls by the evaluation of cortisol concentrations and leucocytes count

A fin de valorar el estrés en toros, se seleccionaron al azar de un matadero de la región centro occidental de Venezuela, un total de 40 toros mestizos Brahman (16 de Brasil y 24 de Venezuela). Se tomaron muestras de sangre para realizar el recuento leucocitario. Igualmente, se determinó la concentración de cortisol mediante la técnica del ELISA competitivo. Los datos fueron analizados usando la prueba no paramétrica U de Mann Whitney. Los resultados del estudio muestran que hubo un incremento no estadísticamente significativo en el recuento diferencial de neutrófilos (53,13% y 43,19%) en toros venezolanos y brasileños, respectivamente. Al mismo tiempo, los toros venezolanos arrojaron un valor de cortisol que fue superior (59,44 ng/dL) y estadísticamente significativo (P≤0,05), cuando se comparó con el de los toros brasileños (40,50 ng/dL). Además, se produjo una disminución no significativa, en el recuento diferencial de eosinófilos (eosinopenia) en ambos grupos, con un promedio de 0,78%. Por otra parte, el recuento diferencial de linfocitos solamente disminuyó significativamente (P≤0,05), en los toros venezolanos (43,25%), mientras que el porcentaje correspondiente a linfocitos de los toros brasileños, se ubicó dentro de los valores normales para la especie (56,19%). Se concluye que los valores elevados de cortisol y neutrófilos, así como también, la eosinopenia y linfopenia encontradas en los toros venezolanos, sugieren un leucograma de estrés, compatible con la conducta nerviosa observada en esos animales. El estrés en los toros brasileños sólo se asoció con una alteración (aumento) de las concentraciones de cortisol y en los valores de eosinófilos. La procedencia y/o tiempo de transporte afectó por igual las concentraciones de cortisol, especialmente en los toros venezolanos. Los cambios sociales observados en los toros venezolanos y brasileños, sugieren la presencia de estrés agudo en los primeros y de estrés crónico en los segundos.

A study was conducted to assess stress in bulls. A total of 40 crossbred Brahman bulls (16 from Brazil and 24 from Venezuela) were selected at random from a slaughterhouse in the Midwestern region of Venezuela. Blood samples were taken for leukocytes count. Also, the cortisol concentration was determined by competitive ELISA technique. Data were analyzed using the nonparametric Mann Whitney U test. The results of the present study show that there was a non-statistically significant increase in neutrophil count (53.13% and 43.19%) in Venezuelan and Brazilian bulls, respectively. At the same time, Venezuelan bulls showed a higher (59.44 ng / dL) cortisol value that was statistically significant (P≤ 0.05), when compared with the Brazilian bulls (40.50 ng/dL). There was also a non- significant decrease in the differential eosinophil count (eosinopenia) in both groups, with an average of 0.78%. On the other hand, the lymphocytes differential count significantly diminished (P≤0.05) in Venezuelan bulls (43.25%) only, while in Brazilian bulls, the percentage corresponding to lymphocytes, was within the normal range for the species (56.19%). It is concluded that that the elevated cortisol and neutrophils levels, as well as the eosinopenia and lymphopenia found in Venezuelan bulls, suggest a stress leukogram, compatible with the nervous behavior observed in those animals. Stress in Brazilian bulls was only associated with an alteration (increase) in cortisol concentrations and in eosinophil values. Both the origin and/or transport time equally affected cortisol concentrations, especially in the Venezuelan bulls. Social changes observed in the Venezuelan and Brazilian bulls, suggest the presence of acute stress in the first and of chronic stress in the latter.