Disseminated cryptococcosis by biological therapy: We must manage the risk / Criptococosis diseminada por terapia biológica, se debe gestionar el riesgo

Introduction: Multiple adverse effects have been described for the biological therapy in autoimmune diseases including many secondary to immunosuppression producing bacterial, fungal, or viral infections. Clinical case: We present the case of a 64-year-old female patient with proven disseminated cryptococcosis secondary to the use of tofacitinib. Other possible causes of immunosuppression such as the human immunodeficiency virus (HIV) were ruled out. The patient had been in treatment for rheumatoid arthritis diagnosed three years before. This drug is a biological agent that inhibits JAK enzymes. Very few cases of pulmonary and meningeal cryptococcosis in this type of patient have been described in the literature. Conclusion: This case report should be useful for other clinicians to bear in mind the possibility of this type of invasive fungal infection associated with biological therapy and to take a risk-management approach.

Introducción. Se han descrito múltiples efectos adversos con el uso de la terapia biológica para enfermedades autoinmunitarias, muchos de ellos secundarios al estado de inmunosupresión, como las infecciones bacterianas, fúngicas o virales. Caso clínico. Se presenta el caso de una mujer de 64 años con diagnóstico comprobado de criptococosis diseminada secundaria al uso de tofacitinib. Se descartaron otras causas de inmunosupresión, como infección por el virus de la inmunodeficiencia humana (HIV). Tres años antes se le había diagnosticado artritis reumatoide y se encontraba en tratamiento farmacológico con un agente biológico que inhibe las enzimas JAK. Se han descrito muy pocos casos de criptococosis pulmonar y meníngea en este tipo de pacientes. Conclusión. Este reporte de caso es útil para que otros médicos tratantes tengan presente la posibilidad de este tipo de infección fúngica invasora asociada con la terapia biológica y el enfoque de gestión de riesgo.

Criptococosis diseminada por terapia biológica, se debe gestionar el riesgo / Disseminated cryptococcosis by biological therapy: We must manage the risk

Introducción. Se han descrito múltiples efectos adversos con el uso de la terapia biológica para enfermedades autoinmunitarias, muchos de ellos secundarios al estado de inmunosupresión, como las infecciones bacterianas, fúngicas o virales. Caso clínico. Se presenta el caso de una mujer de 64 años con diagnóstico comprobado de criptococosis diseminada secundaria al uso de tofacitinib. Se descartaron otras causas de inmunosupresión, como infección por el virus de la inmunodeficiencia humana (HIV). Tres años antes se le había diagnosticado artritis reumatoide y se encontraba en tratamiento farmacológico con un agente biológico que inhibe las enzimas JAK. Se han descrito muy pocos casos de criptococosis pulmonar y meníngea en este tipo de pacientes. Conclusión. Este reporte de caso es útil para que otros médicos tratantes tengan presente la posibilidad de este tipo de infección fúngica invasora asociada con la terapia biológica y el enfoque de gestión de riesgo.

Introduction: Multiple adverse effects have been described for the biological therapy in autoimmune diseases including many secondary to immunosuppression producing bacterial, fungal, or viral infections. Clinical case: We present the case of a 64-year-old female patient with proven disseminated cryptococcosis secondary to the use of tofacitinib. Other possible causes of immunosuppression such as the human immunodeficiency virus (HIV) were ruled out. The patient had been in treatment for rheumatoid arthritis diagnosed three years before. This drug is a biological agent that inhibits JAK enzymes. Very few cases of pulmonary and meningeal cryptococcosis in this type of patient have been described in the literature. Conclusion: This case report should be useful for other clinicians to bear in mind the possibility of this type of invasive fungal infection associated with biological therapy and to take a risk-management approach.

[Integrated Care Protocol: Hypertension]. / Protocolo de Atención Integral: hipertensión arterial sistémica.

Background: Hypertension is the most common cardiovascular risk factor that is responsible for complications such as cerebrovascular events, heart failure, acute myocardial infarction, kidney failure, arrhythmias and blindness. About 30% of the adult population older than 20 years is a carrier. 40% of carriers are unaware of suffering from it since its onset is generally asymptomatic. Unfortunately, of those who are already known to be hypertensive, only half take drug treatment and of these, only half achieve control figures (<14/90 mmHg). For several decades it has not been possible to forcefully modify the natural history of this disease despite the advancement of therapeutic drugs. The Mexican Institute of Social Security launches the initiative of the Integrated Care Protocols (PAI) of the main diseases. This protocol shows how the three levels of medical care are concatenated, the role of each of the members of the multidisciplinary team for medical care, including: doctor, nurse, social work, psychologist, nutritionist, among others and, to patient sharing. The main changes in diagnostic criteria, in-office and out-of-office blood pressure measurement, drug therapy (monotherapy, dual therapy and triple therapy) and non-drug therapy, and follow-up are presented. The diagnostic-therapeutic approach using algorithm as well as the diagnostic approach to secondary hypertension and special forms of hypertension such as in pregnancy, hypertensive crisis, hypertension in the elderly, ischemic or nephropathy patients.

Introducción: la hipertensión arterial sistémica (HAS) es el factor de riesgo cardiovascular más común y es responsable de complicaciones como evento cerebrovascular, insuficiencia cardiaca, infarto agudo de miocardio, insuficiencia renal, arritmias y ceguera. Alrededor del 30% de la población adulta mayor de 20 años es portadora. El 40% de los portadores ignoran padecerla ya que su inicio generalmente es asintomático. Desafortunadamente de los que ya se saben hipertensos solo la mitad toma tratamiento farmacológico y de estos, tan solo la mitad logra cifras de control (< 140/90 mmHg). Durante varias décadas no se ha logrado de forma contundente modificar la historia natural de esta enfermedad pese al avance fármaco terapéutico. El Instituto Mexicano del Seguro Social, lanza la iniciativa de los Protocolos de Atención Integral (PAI) de las principales enfermedades. En el presente protocolo se muestra cómo se concatenan los tres niveles de atención médica, el papel de cada uno de los integrantes del equipo multidisciplinario para la atención médica, incluyendo: médico, enfermera, trabajo social, psicólogo, nutricionista, entre otros y, la coparticipación del paciente. Se presentan los principales cambios en criterios diagnósticos, medición de la presión arterial dentro y fuera de consultorio, terapéutica farmacológica (monoterapia, terapia dual y terapia triple), no farmacológica y seguimiento. El Abordaje diagnóstico-terapéutico usando algoritmos, así como también el abordaje diagnóstico de la hipertensión secundaria y formas especiales de hipertensión tales como en el embarazo, crisis hipertensivas, hipertensión en el adulto mayor, pacientes isquémicos o con nefropatía.

[PRIISMA Project: Transformation into a more preventive, resilient, comprehensive, innovative, sustainable, modern and accessible IMSS]. / Proyecto PRIISMA: transformación hacia un IMSS más preventivo, resiliente, integral, innovador, sostenible, moderno y accesible.

Two years after the onset of the COVID-19 pandemic, the Mexican Institute for Social Security (IMSS, according to its initials in Spanish) rethought new projects focused on the new needs of the population and social security organizations and institutions. The Institute, as a cornerstone in the search for the wellbeing of Mexicans, aligned with the National Development Plan and the Strategic Health for Wellbeing Program, sought to direct its transformation towards a preventive, resilient, comprehensive, innovative, sustainable, modern and accessible IMSS. For this reason, the Medical Services Director designed the PRIISMA Project, as the one that over the next three years could make possible to innovate and improve its medical care processes, starting with the recovery of medical services and identifying those groups of beneficiaries who experience the most vulnerable circumstances. The PRIISMA project consisted of five sub-projects: 1. Vulnerable groups; 2. Efficient and effective care; 3. Prevent IMSS plus; 4 IMSS University and 5. Recovery of medical services. The strategies of each project seek to improve medical care for all IMSS beneficiaries and users with a human rights perspective and by priority groups; the goal is reducing the gaps in access to health care, leaving no one behind and leaving no one out; and to surpass the goals for medical services provided before the pandemic. This document provides an overview of strategies and progress of the PRIISMA sub-projects achieved during 2022.

Después de dos años del inicio de la pandemia por COVID-19, el Instituto Mexicano del Seguro Social (IMSS) se replanteó nuevos proyectos enfocados a las nuevas necesidades de la población y de las organizaciones e instituciones de salud y seguridad social. El Instituto, como piedra angular de la búsqueda del bienestar de las mexicanas y mexicanos, alineado al Plan Nacional de Desarrollo y al Programa Estratégico de Salud para el Bienestar, buscó dirigir su transformación hacia un IMSS más preventivo, resiliente, integral, innovador, sostenible, moderno y accesible. Por ello la Dirección de Prestaciones Médicas diseñó el Proyecto PRIISMA, el cual durante los próximos tres años permitirá innovar y mejorar sus procesos de atención médica, comenzando con la recuperación de los servicios médicos y la identificación de aquellos grupos de derechohabientes que experimentan mayores circunstancias en situación de vulnerabilidad. El Proyecto PRIISMA está constituido por cinco subproyectos: 1) grupos en situación de vulnerabilidad; 2) atención eficiente y eficaz; 3) PrevenIMSS más; 4) Universidad IMSS, y 5) recuperación de servicios médicos. Las estrategias de cada proyecto buscan mejorar la atención médica de todos los derechohabientes y usuarios del IMSS con perspectiva de derechos humanos y por grupos prioritarios; se trata de reducir las brechas para el acceso a la salud sin dejar a nadie atrás y a nadie fuera; además, con ellas se busca superar las metas de atención de servicios médicos otorgados antes de la pandemia. El presente documento da a conocer los porqués, las estrategias y los avances de los subproyectos PRIISMA logrados durante el 2022.

No Association Between Bone Mineral Density and Breast Arterial Calcification Among Postmenopausal Women.

CONTEXT: The association between bone mineral density (BMD) and breast arterial calcification (BAC) remains poorly understood and controversial. OBJECTIVE: The objective of this article is to examine the association between BMD and BAC in a large cohort of postmenopausal women undergoing routine mammography. DESIGN: A cross-sectional analysis of baseline data from a multiethnic cohort was performed. SETTING: The setting for this analysis is an integrated health care delivery system in Northern California in the United States. PATIENTS: A total of 1273 women age 60 to 79 years (mean age, 67 years) were recruited within 12 months of screening mammography. MAIN OUTCOME MEASURE: A BAC score (mg) was obtained from digital mammograms using a novel densitometry method. BAC presence was defined as a BAC score greater than 0 mg, and severe BAC as a BAC score greater than 20 mg. RESULTS: Overall, 53% of women had osteopenia and 21% had osteoporosis. The prevalence of BAC greater than 0 mg was 29%, 30%, and 29% among women with normal BMD, osteopenia, and osteoporosis, respectively (P = 0.98). The prevalence of BAC greater than 20 mg was 5%, 3%, and 5% among women with normal BMD, osteopenia and osteoporosis, respectively (P = .65). The odds ratios (ORs) of BAC greater than 0 mg vs BAC = 0 mg after multivariable adjustment were 1.09 (95% CI, 0.81-1.48; P = .54) for osteopenia and 0.99 (95% CI, 0.69-1.48; P = .98) for osteoporosis. The adjusted ORs for BAC greater than 20 mg vs BAC 20 mg or less were 1.03 (95% CI, 0.52-2.01; P = .93) for osteopenia and 1.89 (95 CI, 0.81-4.47; P = .14) for osteoporosis. CONCLUSION: Our findings do not support an association of either osteopenia or osteoporosis with BAC presence or severity among postmenopausal women.

Vertical flow wetlands and hybrid systems for the treatment of landfill leachate.

Landfill leachates contain a variety of toxic compounds, which makes them one of the most difficult types of wastewater to be treated. An alternative "green" technology for leachate treatment is the use of constructed wetlands (CWs). The aims of this study were to select macrophytes and substrates to be used in vertical flow wetlands (VFWs) and to evaluate the performance of hybrid systems composed by a VFW and a horizontal subsurface flow (HSSW) or a free water surface flow (FWSW) wetlands for the treatment of a high ammonium concentration landfill leachate. In microcosms scale experiments, Typha domingensis, Scirpus californicus, and Iris pseudacorus were studied to assess their tolerance to raw and diluted leachate. Substrate selection for VFWs was evaluated using different layers of light expanded clay aggregate (LECA), coarse sand, fine sand, and gravel. Contaminant removals were higher in planted than in unplanted wetlands. Plants did not tolerate the raw effluent but showed a positive effect on plant growth when exposed to the diluted leachate. T. domingensis and I. pseudacorus showed higher contaminant removal ability and tolerance to landfill leachate than S. californicus. VFW with LECA + coarse sand showed the best performance in removal efficiencies. Hybrid system composed by VFW-FWSW planted with T. domingensis presented the best performance for the treatment of landfill leachate with high concentrations of ammonium.

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.

MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease: cohort recruitment and baseline characteristics.

PURPOSE: MultIethNic Study of BrEast ARterial Calcium Gradation and CardioVAscular Disease (MINERVA) was designed to answer the question of whether a novel continuous breast arterial calcification (BAC) mass score improves cardiovascular risk stratification among asymptomatic postmenopausal women. This article describes recruitment and baseline characteristics. METHODS: MINERVA is a multiethnic longitudinal cohort study. The phenotype data include BAC mass by densitometry applied to digital mammograms, sociodemographic factors, self-reported medical history, medications, parental history, reproductive history, smoking, alcohol consumption, physical activity, anthropometry, ankle-brachial index, blood pressure, laboratory panel, breast volumes, cognitive function, bioelectrical impedance, habitual diet, dietary supplements, sleep, psychosocial factors, and sun exposure. RESULTS: A total of 5145 women aged 60 to 79 years with available digital, uncompressed mammograms were recruited from the membership of Kaiser Permanente of Northern California between October 24, 2012 and February 13, 2015 and completed a baseline clinic visit or an abbreviated phone questionnaire. Of those, 4153 underwent phlebotomy and have blood biomarkers. Overall prevalence of BAC was 26%, and it varied by age and race. The mean (SD) BAC mass was 12 (23) mg and the range 0-342 mg. CONCLUSIONS: MINERVA is the first cohort with a continuous measure of BAC. The cohort is large, ethnically diverse, and deeply phenotyped in terms of socioeconomic, behavioral, and clinical factors, and blood biomarkers.

Corexit, oil and marine microgels.

Corexit, an EPA-approved chemical dispersant, was intensively used during the 2010 Deepwater Horizon Oil Spill in the Gulf of Mexico. Current studies surrounding Corexit have mainly focused on its toxicity and oil removal capacity. The potential impact of Corexit on the surface ocean carbon dynamics has remained largely unknown. The spontaneous assembly of DOM (dissolved organic matter) polymers into microgels (POM, particulate organic matter) was demonstrated previously that it can influence various critical processes, such as colloidal pump, microbial loops, and nutrition availability in the surface ocean. Here, we report that Corexit alone can significantly inhibit DOM microgel formation and reduce the stability of pre-existing microgels. However, Corexit and oil, Chemically Enhanced Water Accommodated Fraction (CEWAF), could effectively facilitate DOM microgel formation. The unanticipated disturbance of Corexit and oil spills on the critical DOM-POM continuum warrant particular caution and thus should be considered for future application of Corexit during oil spills.

Dysfunctional immunometabolic effects of vitamin D deficiency, increased cardiometabolic risk. Potential epidemiological alert in America? / Efectos inmunometabólicos disfuncionales de la deficiencia de vitamina D y aumento de riesgo cardiometabólico. ¿Potencial alerta epidemiológica en América?

Vitamin D deficiency is a serious public health problem worldwide that affects not only skeletal health, but also a wide range of acute and chronic diseases. However, there is still skepticism because of the lack of randomized, controlled trials to support association studies on the benefits of vitamin D for non-skeletal health. This review was based on articles published during the 1980-2015 obtained from the Cochrane Central Register of controlled trials, MEDLINE and PubMed, and focuses on recent challenges with regard to the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D levels from dietary sources, supplements, and sun exposure. The effect of vitamin D on epigenetic fetal programming and regulation of genes that may potentially explain why vitamin D could have such lifelong comprehensive health benefits is reviewed. Optimization of vitamin D levels in children and adults around the world has potential benefits to improve skeletal health and to reduce the risk of chronic diseases, including some types of cancer, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, and severe cardiovascular disorders such as atherothrombosis, neurocognitive disorders, and mortality.

Efectos inmunometabólicos disfuncionales de la deficiencia de vitamina D y aumento de riesgo cardiometabólico. ¿Potencial alerta epidemiológica en América? / Dysfunctional immunometabolic effects of vitamin D deficiency, increased cardiometabolic risk. Potential epidemiological alert in America?

La deficiencia de vitamina D es un problema grave de salud pública en todo el mundo y que afecta no solo la salud músculo-esquelética sino también una amplia gama de enfermedades agudas y crónicas, incluyendo las no trasmisibles de riesgo cardiovascular, algunas enfermedades autoinmunes, metabólicas y mecanismos fisiopatológicos en obesidad. Sin embargo, subsiste el escepticismo de la falta de ensayos controlados aleatorizados para apoyar los estudios de asociación sobre los beneficios de salud no esqueléticos de vitamina D. Los artículos en los que se basó esta revisión fueron obtenidos de las bases de datos de MEDLINE, PubMed de 1980-2015 con respecto a la definición de deficiencia de vitamina D y su participación en trastornos proinflamatorios, inmunometabólicos y factores de riesgo cardiovascular. Se revisan las acciones de la vitamina D sobre la programación epigenética fetal y regulación de los genes que potencialmente podrían explicar por qué la vitamina D podría tener tales beneficios para la salud a lo largo de la vida en el humano. Hay potencialmente una ventaja en optimizar los niveles de la vitamina D de niños y adultos mayores en todo el mundo para mejorar no solo la salud músculo-esquelética, sino también para reducir el riesgo de enfermedades crónicas, incluyendo algunos factores de riesgo cardiovascular, así como ciertos tipos de cáncer, enfermedades autoinmunes, enfermedades infecciosas, diabetes mellitus tipo 2, trastornos cardiovasculares, incluyendo aterotrombosis, alteraciones neurocognitivas y, como consecuencia sobre la morbimortalidad global (AU)

Vitamin D deficiency is a serious public health problem worldwide that affects not only skeletal health, but also a wide range of acute and chronic diseases. However, there is still skepticism because of the lack of randomized, controlled trials to support association studies on the benefits of vitamin D for non-skeletal health. This review was based on articles published during the 1980-2015 obtained from the Cochrane Central Register of controlled trials, MEDLINE and PubMed, and focuses on recent challenges with regard to the definition of vitamin D deficiency and how to achieve optimal serum 25-hydroxyvitamin D levels from dietary sources, supplements, and sun exposure. The effect of vitamin D on epigenetic fetal programming and regulation of genes that may potentially explain why vitamin D could have such lifelong comprehensive health benefits is reviewed. Optimization of vitamin D levels in children and adults around the world has potential benefits to improve skeletal health and to reduce the risk of chronic diseases, including some types of cancer, autoimmune diseases, infectious diseases, type 2 diabetes mellitus, and severe cardiovascular disorders such as atherothrombosis, neurocognitive disorders, and mortality (AU)

Characterization of systemic and pneumonic murine models of plague infection using a conditionally virulent strain.

Yersinia pestis causes bubonic and pneumonic plague in humans. The pneumonic infection is the most severe and invariably fatal if untreated. Because of its high virulence, ease of delivery and precedent of use in warfare, Y. pestis is considered as a potential bioterror agent. No licensed plague vaccine is currently available in the US. Laboratory research with virulent strains requires appropriate biocontainment (i.e., Biosafety Level 3 (BSL-3) for procedures that generate aerosol/droplets) and secure facilities that comply with federal select agent regulations. To assist in the identification of promising vaccine candidates during the early phases of development, we characterized mouse models of systemic and pneumonic plague infection using the Y. pestis strain EV76, an attenuated human vaccine strain that can be rendered virulent in mice under in vivo iron supplementation. Mice inoculated intranasally or intravenously with Y. pestis EV76 in the presence of iron developed a systemic and pneumonic plague infection that resulted in disease and lethality. Bacteria replicated and severely compromised the spleen, liver and lungs. Susceptibility was age dependent, with younger mice being more vulnerable to pneumonic infection. We used these models of infection to assess the protective capacity of newly developed Salmonella-based plague vaccines. The protective outcome varied depending on the route and dose of infection. Protection was associated with the induction of specific immunological effectors in systemic/mucosal compartments. The models of infection described could serve as safe and practical tools for identifying promising vaccine candidates that warrant further potency evaluation using fully virulent strains in BSL-3 settings.

Prevalence of osteonecrosis of the jaw in patients with oral bisphosphonate exposure.

PURPOSE: Osteonecrosis of the jaw (ONJ) is a serious complication associated with bisphosphonate therapy, but its epidemiology in the setting of oral bisphosphonate therapy is poorly understood. The present study examined the prevalence of ONJ in patients receiving chronic oral bisphosphonate therapy. MATERIALS AND METHODS: We mailed a survey to 13,946 members who had received chronic oral bisphosphonate therapy as of 2006 within a large integrated health care delivery system in Northern California. Respondents who reported ONJ, exposed bone or gingival sores, moderate periodontal disease, persistent symptoms, or complications after dental procedures were invited for examination or to have their dental records reviewed. ONJ was defined as exposed bone (of >8 weeks' duration) in the maxillofacial region in the absence of previous radiotherapy. RESULTS: Of the 8,572 survey respondents (71 +/- 9 years, 93% women), 2,159 (25%) reported pertinent dental symptoms. Of these 2,159 patients, 1,005 were examined and an additional 536 provided dental records. Nine ONJ cases were identified, representing a prevalence of 0.10% (95% confidence interval 0.05% to 0.20%) among the survey respondents. Of the 9 cases, 5 had occurred spontaneously (3 in palatal tori) and 4 occurred in previous extraction sites. An additional 3 patients had mandibular osteomyelitis (2 after extraction and 1 with implant failure) but without exposed bone. Finally, 7 other patients had bone exposure that did not fulfill the criteria for ONJ. CONCLUSIONS: ONJ occurred in 1 of 952 survey respondents with oral bisphosphonate exposure (minimum prevalence of 1 in 1,537 of the entire mailed cohort). A similar number had select features concerning for ONJ that did not meet the criteria. The results of the present study provide important data on the spectrum of jaw complications among patients with oral bisphosphonate exposure.