Electroencephalography signals and neurodevelopment after Kawasaki disease: A pilot study.

BACKGROUND: Acute Kawasaki disease (KD) induces central nervous system inflammation and excessive irritability. Long-term impacts on children's neurodevelopment have only been studied marginally. This pilot study aimed to describe the neuropsychological profile of primary school-aged children with a history of KD and to explore the impacts of KD on electroencephalography (EEG) markers associated with attention and brain maturation. METHODS: Fifteen children (8.8 ± 2.5 years) were recruited 4.9 ± 2.7 years after KD onset. Intellectual abilities, long-term memory, and auditory sustained attention were evaluated. Parents completed standardized questionnaires assessing (1) executive functioning; (2) internalizing and externalizing difficulties; (3) attention deficit hyperactivity disorder symptoms; and (4) autism spectrum disorder symptoms. Theta/beta ratio (TBR) and alpha peak (AP) were extracted from resting-state EEG and compared with 32 controls (8.9 ± 2.1 years). The alpha band was analyzed using a feature reduction algorithm to detect potential groupings. RESULTS: Performances showed preserved intellectual abilities and memory. Sustained attention performance was within the lower range for 4/14 participants (29%), with considerable parental reports of inattention (43%), working memory difficulties (50%), and hyperactivity-impulsivity (36%). No alterations in the TBR were found but the KD group presented a significantly lower AP amplitude ratio. A clear separation of KD cohort into two clusters showed that acute irritability is associated with a weaker AP. CONCLUSIONS: Despite overall preserved cognitive functions, there is a possible association between KD and attention deficit concerns. This first EEG-based study indicates alpha peak abnormality after KD, predominantly in children with acute irritability. Longitudinal studies are warranted to better characterize patients' neurodevelopmental trajectory.

Glycine: The Smallest Anti-Inflammatory Micronutrient.

Glycine is a non-essential amino acid with many functions and effects. Glycine can bind to specific receptors and transporters that are expressed in many types of cells throughout an organism to exert its effects. There have been many studies focused on the anti-inflammatory effects of glycine, including its abilities to decrease pro-inflammatory cytokines and the concentration of free fatty acids, to improve the insulin response, and to mediate other changes. However, the mechanism through which glycine acts is not clear. In this review, we emphasize that glycine exerts its anti-inflammatory effects throughout the modulation of the expression of nuclear factor kappa B (NF-κB) in many cells. Although glycine is a non-essential amino acid, we highlight how dietary glycine supplementation is important in avoiding the development of chronic inflammation.

Kawasaki Disease Arab Initiative [Kawarabi]: Establishment and Results of a Multicenter Survey.

Studies on Kawasaki disease (KD) in Arab countries are scarce, often providing incomplete data. This along with the benefits of multicenter research collaboratives led to the creation of the KD Arab Initiative [Kawarabi] consortium. An anonymous survey was completed among potential collaborative Arab medical institutions to assess burden of KD in those countries and resources available to physicians. An online 32-item survey was distributed to participating institutions after conducting face validity. One survey per institution was collected. Nineteen physicians from 12 countries completed the survey representing 19 out of 20 institutions (response rate of 95%). Fifteen (79%) institutions referred to the 2017 American Heart Association guidelines when managing a patient with KD. Intravenous immunoglobulin (IVIG) is not readily available at 2 institutions (11%) yet available in the country. In one center (5%), IVIG is imported on-demand. The knowledge and awareness among countries' general population was graded (0 to 10) at median/interquartiles (IQR) 3 (2-5) and at median/IQR 7 (6-8) in the medical community outside their institution. Practice variations in KD management and treatment across Arab countries require solid proactive collaboration. The low awareness and knowledge estimates about KD among the general population contrasted with a high level among the medical community. The Kawarabi collaborative will offer a platform to assess disease burden of KD, among Arab population, decrease practice variation and foster population-based knowledge.

Profile of Treatment-Seeking Gaming Disorder Patients: A Network Perspective.

The increasing presence of gaming disorder in recent years has led to major efforts to identify the specific predictors that have a high impact on the profile of people seeking treatment for this mental condition. The purpose of this study was to explore the network structure of the correlates of gaming disorder considering sociodemographic features and other clinical symptoms. Network analysis was applied to a sample of patients who met clinical criteria for gaming disorder (n = 117, of ages ranging from 15 to 70 yrs-old). Variables considered in the network included sex, age, socioeconomic position, global emotional distress, age of onset and duration of the gaming disorder, personality traits and the presence of other addictive behaviors (tobacco, alcohol and behavioral addictions). The central nodes in the network were global psychological distress, chronological age, and age of onset of gaming related problems. Linkage analysis also identified psychopathological status and age as the variables with the most valuable information in the model. The poorest relevance in the analysis was for the duration of gaming problems and socioeconomic levels. Modularity analysis grouped the nodes within four clusters. Identification of the variables with the highest centrality/linkage can be particularly useful for developing precise management plans to prevent and treat gaming disorder related problems.

BETA-HYDROXYBUTYRATE COUNTERACTS THE DELETERIOUS EFFECTS OF A SATURATED HIGH-FAT DIET ON SYNAPTIC AMPA RECEPTORS AND COGNITIVE PERFORMANCE.

The ketogenic diet, characterized by high fat and low carbohydrates, has gained popularity not only as a strategy for managing body weight but also for its efficacy in delaying cognitive decline associated with neurodegenerative diseases and the aging process. Since this dietary approach stimulates the liver's production of ketone bodies, primarily ß-hydroxybutyrate (BHB), which serves as an alternative energy source for neurons, we investigated whether BHB could mitigate impaired AMPA receptor trafficking, synaptic dysfunction, and cognitive decline induced by metabolic challenges such as saturated fatty acids. Here, we observe that, in cultured primary cortical neurons, exposure to palmitic acid (200µM) decreased surface levels of glutamate GluA1-containing AMPA receptors, whereas unsaturated fatty acids, such as oleic acid and ω-3 docosahexaenoic acid (200µM), and BHB (5mM) increased them. Furthermore, BHB countered the adverse effects of palmitic acid on synaptic GluA1 levels in hippocampal neurons, as well as excitability and plasticity in hippocampal slices. Additionally, daily intragastric administration of BHB (100 mg/kg/day) for two months reversed cognitive impairment induced by a saturated high-fat diet (49% of calories from fat) in a mouse experimental model of obesity. In summary, our findings underscore the significant impact of fatty acids and ketone bodies on AMPA receptors abundance, synaptic function and neuroplasticity, shedding light on the potential use of BHB to delay cognitive impairments associated with metabolic diseases.

Modulator Effect of AT1 Receptor Knockdown on THP-1 Macrophage Proinflammatory Activity.

Currently, it is known that angiotensin II (AngII) induces inflammation, and an AT1R blockade has anti-inflammatory effects. The use of an AT1 receptor antagonist promotes the inhibition of the secretion of multiple proinflammatory cytokines in macrophages, as well as a decrease in the concentration of reactive oxygen species. The aim of this study was to determine the effect of AT1 receptor gene silencing on the modulation of cytokines (e.g., IL-1ß, TNF-α, and IL-10) in THP-1 macrophages and the relation to the gene expression of NF-κB. MATERIALS AND METHODS: We evaluated the gene expression of PPAR-γ in THP-1 macrophages using PMA (60 ng/mL). For the silencing, cells were incubated with the siRNA for 72 h and telmisartan (10 µM) was added to the medium for 24 h. After that, cells were incubated during 1 and 24 h, respectively, with Ang II (1 µM). The gene expression levels of AT1R, NF-κB, and cytokines (IL-1ß, TNF-α, and IL-10) were measured by RT-qPCR. RESULTS: We observed that silencing of the AT1 receptor causes a decrease in the expression of mRNA of proinflammatory cytokines (IL-1ß and TNF-α), NF-κB, and PPAR-γ. CONCLUSIONS: We conclude that AT1R gene silencing is an alternative to modulating the production of proinflammatory cytokines such as TNF-α and IL-1ß via NF-κB in macrophages and having high blood pressure decrease.

Feeding the Brain: Effect of Nutrients on Cognition, Synaptic Function, and AMPA Receptors.

In recent decades, traditional eating habits have been replaced by a more globalized diet, rich in saturated fatty acids and simple sugars. Extensive evidence shows that these dietary factors contribute to cognitive health impairment as well as increase the incidence of metabolic diseases such as obesity and diabetes. However, how these nutrients modulate synaptic function and neuroplasticity is poorly understood. We review the Western, ketogenic, and paleolithic diets for their effects on cognition and correlations with synaptic changes, focusing mainly (but not exclusively) on animal model studies aimed at tracing molecular alterations that may contribute to impaired human cognition. We observe that memory and learning deficits mediated by high-fat/high-sugar diets, even over short exposure times, are associated with reduced arborization, widened synaptic cleft, narrowed post-synaptic zone, and decreased activity-dependent synaptic plasticity in the hippocampus, and also observe that these alterations correlate with deregulation of the AMPA-type glutamate ionotropic receptors (AMPARs) that are crucial to neuroplasticity. Furthermore, we explored which diet-mediated mechanisms modulate synaptic AMPARs and whether certain supplements or nutritional interventions could reverse deleterious effects, contributing to improved learning and memory in older people and patients with Alzheimer's disease.

Glycine Effect on the Expression Profile of Orphan Receptors GPR21, GPR26, GPR39, GPR82 and GPR6 in a Model of Inflammation in 3T3-L1 Cells.

BACKGROUND: Chronic or low-grade inflammation is a process where various immune cells are recruited from the periphery into adipose tissue. This event gives rise to localised inflammation, in addition to having a close interaction with cardiometabolic pathologies where the mediation of orphan receptors is observed. The aim of this study was to analyse the participation of the orphan receptors GPR21, GPR39, GPR82 and GPR6 in a chronic inflammatory process in 3T3-L1 cells. The 3T3-L1 cells were stimulated with TNF-α (5 ng/mL) for 60 min as an inflammatory model. Gene expression was measured by RT-qPCR. RESULTS: We showed that the inflammatory stimulus of TNF-α in adipocytes decreased the expression of the orphan receptors GPR21, GPR26, GPR39, GPR82 and GPR6, which are related to low-grade inflammation. CONCLUSIONS: Our results suggest that GPR21 and GPR82 are modulated by glycine, it shows a possible protective role in the presence of an inflammatory environment in adipocytes, and they could be a therapeutic target to decrease the inflammation in some diseases related to low-grade inflammation such as diabetes, obesity and metabolic syndrome.

[SARS-COV-2 infection in patients with hematological malignancies and transplants]. / Infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y trasplantes.

SARS-CoV-2 infection in patients with hematological malignancies and hematopoietic stem cell transplants (HSCT) can be severe and with significant mortality. We carried out a prospective and observational study to describe the clinical and epidemiological characteristics and outcome of SARS-CoV-2 infection in patients with hematological malignancies and HSCT. Twenty adult patients were included with a median age of 58 years and a median Charlson score of 3. Infections were community-acquired and nosocomial in 60% and 40%, respectively, and 30% of the patients had a history of contact with a SARS-CoV-2 infected person. Sixty-five percent had pulmonary infiltrates, mostly with a ground-glass pattern on CT scan. Almost half of the patients had a severe and critical illness, and a high proportion received convalescent plasma as treatment. Twenty percent and 15% had complications and hospital infections, respectively, and had prolonged hospitalization expressed as median days of it. The 30-day mortality was 10%. SARS-CoV-2 infection in our population had a considerable clinical and epidemiological impact.

La infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y trasplantes de células progenitoras hematopoyéticas (TCPH) puede ser grave y con importante mortalidad. Llevamos a cabo un estudio prospectivo y observacional que tuvo como objetivo describir las características clínicas, epidemiológicas y la evolución de la infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y TCPH. Se incluyeron 20 pacientes adultos con una mediana de edad de 58 años y una mediana de score de Charlson de 3. Las infecciones fueron de adquisición comunitaria y nosocomial en el 60% y 40% respectivamente, y el 30% de los pacientes tenía antecedente de contacto con una persona infectada por SARS-CoV-2. El 65% presentó infiltrados pulmonares, mayormente con patrón de vidrio esmerilado en la tomografía computarizada de tórax. Casi la mitad de los pacientes tuvo enfermedad grave y crítica, y una alta proporción recibió plasma de convalecientes como tratamiento. Presentaron complicaciones e infecciones hospitalarias el 20% y 15% respectivamente, y tuvieron una mediana de días de internación prolongada. La mortalidad a 30 días fue del 10%. La infección por SARS-CoV-2 en nuestra población tuvo considerable impacto clínico y epidemiológico.

Antibiotic Consumption and Its Relationship with Bacterial Resistance Profiles in ESKAPE Pathogens in a Peruvian Hospital.

A descriptive design was carried out studying the correlation between antimicrobial consumption and resistance profiles of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) in a Peruvian hospital, including the surgical, clinical areas and the intensive care unit (ICU) during the time period between 2015 and 2018. There was a significant correlation between using ceftazidime and the increase of carbapenem-resistant Pseudomonas aeruginosa isolations (R = 0.97; p < 0.05) and the resistance to piperacillin/tazobactam in Enterobacter spp. and ciprofloxacin usage (R = 0.97; p < 0.05) in the medical wards. The Pseudomonas aeruginosa resistance to piperacillin/tazobactam and amikacin in the intensive care unit (ICU) had a significant reduction from 2015 to 2018 (67% vs. 28.6%, 65% vs. 34.9%, p < 0.001). These findings give valuable information about the rates and dynamics in the relationship between antibiotic usage and antimicrobial resistance patterns in a Peruvian hospital and reinforce the need for continuous support and assessment of antimicrobial stewardship strategies, including microbiological indicators and antimicrobial consumption patterns.

Factors related to the dual condition of gambling and gaming disorders: A path analysis model.

BACKGROUND AND AIMS: Gaming disorder has experienced rapid growth in the last decade among youth and adult populations, in parallel to the expansion of the videogame industry. The objective of this study was to explore the underlying process to explain the dual diagnosis of gaming with gambling disorder. METHODS: The sample included n = 117 patients who met clinical criteria for gaming disorder, recruited from a tertiary care unit specialized in the treatment of behavioral addictions. Path analysis (implemented through structural equation modeling) assessed the direct and mediational mechanisms between the dual condition of gaming + gambling disorder and sociodemographic variables and personality traits. RESULTS: The comorbid gaming + gambling disorder was met for 14.5% of the participants (additionally, 6.0% of the sample also met criteria for problematic gambling). The dual diagnosis was directly related to an older age at onset of the addiction problems, a higher level of the novelty seeking trait and being in active work. Employment status also mediated the relationship between persistence levels and chronological age. Greater psychopathological distress was related to females, higher levels of harm avoidance and persistence and lower levels of self-directedness. CONCLUSIONS: The results of this study provide empirical evidence for the specific factors that increase the likelihood of the dual gaming + gambling disorder. Clinical settings should consider these features to improve gaming diagnosis and treatment. Preventive programs should also be focused on the most vulnerable groups to prevent onset and progression of this comorbid condition.

Effect of allergen-specific immunotherapy with purified Alt a1 on AMP responsiveness, exhaled nitric oxide and exhaled breath condensate pH: a randomized double blind study.

BACKGROUND: Little information is available on the effect of allergen-specific immunotherapy on airway responsiveness and markers in exhaled air. The aims of this study were to assess the safety of immunotherapy with purified natural Alt a1 and its effect on airway responsiveness to direct and indirect bronchoconstrictor agents and markers in exhaled air. METHODS: This was a randomized double-blind trial. Subjects with allergic rhinitis with or without mild/moderate asthma sensitized to A alternata and who also had a positive skin prick test to Alt a1 were randomized to treatment with placebo (n = 18) or purified natural Alt a1 (n = 22) subcutaneously for 12 months. Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine, exhaled nitric oxide (ENO), exhaled breath condensate (EBC) pH, and serum Alt a1-specific IgG4 antibodies were measured at baseline and after 6 and 12 months of treatment. Local and systemic adverse events were also registered. RESULTS: The mean (95% CI) allergen-specific IgG4 value for the active treatment group increased from 0.07 µg/mL (0.03-0.11) at baseline to 1.21 µg/mL (0.69-1.73, P < 0.001) at 6 months and to 1.62 µg/mL (1.02-2.22, P < 0.001) at 12 months of treatment. In the placebo group, IgG4 value increased nonsignificantly from 0.09 µg/mL (0.06-0.12) at baseline to 0.13 µg/mL (0.07-0.18) at 6 months and to 0.11 µg/mL (0.07-0.15) at 12 months of treatment. Changes in the active treatment group were significantly higher than in the placebo group both at 6 months (P < 0.001) and at 12 months of treatment (P < 0.0001). However, changes in AMP and methacholine responsiveness, ENO and EBC pH levels were not significantly different between treatment groups. The overall incidence of adverse events was comparable between the treatment groups. CONCLUSION: Although allergen-specific immunotherapy with purified natural Alt a1 is well tolerated and induces an allergen-specific IgG4 response, treatment is not associated with changes in AMP or methacholine responsiveness or with significant improvements in markers of inflammation in exhaled air. These findings suggest dissociation between the immunotherapy-induced increase in IgG4 levels and its effect on airway responsiveness and inflammation.

Development and Validation of the Social Network Addiction Scale (SNAddS-6S).

The use of social networks has increased exponentially, especially among youth. These tools offer many advantages but also carry some risks such as addiction. This points to the need for a valid multifactorial instrument to measure social network addiction, focusing on the core components of addiction that can serve researchers and practitioners. This study set out to validate a reliable multidimensional social network addiction scale based on the six core components of addiction (SNAddS-6S) by using and adapting the Bergen Facebook Addiction Scale. A total of 369 users of social networks completed a questionnaire. Exploratory and confirmatory factor analyses were performed, and different competing models were explored. The external validity of the scale was tested across its relations with different measures. Evidence for the validity and reliability of both the multidimensional SNAddS-6S and the unidimensional Short SNAddS-6S was provided. The SNAddS-6S was composed of 18 items and five different factors (time-management, mood modification, relapse, withdrawal, and conflict), with the time-management factor as a higher-order factor integrated by salience and tolerance as sub-factors. The Short SNAddS-6S was composed of six items and a unifactorial structure. This scale could be of relevance for researchers and practitioners to assess the extent to which individuals suffer from social network addiction and to study the potential predictors and risks of such addiction.

Differences in the response to methacholine between the tidal breathing and dosimeter methods: influence of the dose of bronchoconstrictor agent delivered to the mouth.

BACKGROUND: It has been postulated that differences in provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) values between the dosimeter method and tidal breathing method might be due to differences in the dose of agonist delivered to the mouth. The aim of the present study was to determine the influence of the dose of aerosol delivered to the mouth on differences in the response obtained with each challenge method. METHODS: This study measured airway responsiveness to methacholine by dosimeter method and tidal breathing method in 27 subjects with suspected asthma. The dosimeter was modified to deliver an identical volume to that obtained with the tidal breathing method. Concentration-response curves were characterized by the PC20. RESULTS: The dosimeter method PC20 was significantly higher than the tidal breathing method PC20, with geometric mean values of 4.03 (95% confidence interval [CI], 1.86 to 8.78 mg/mL) and 2.19 (95% CI, 1.32 to 3.64 mg/mL; p = 0.04), respectively. The mean difference in the PC20 value detected with each method was similar in subjects with tidal breathing method PC20 values > or = 2 mg/mL (0.77 doubling concentrations) and in those with PC20 values < 2 mg/mL (0.96 doubling concentrations; p = 0.83). CONCLUSIONS: The tidal breathing method produces PC20 values significantly lower than a modified dosimeter method, which delivers the same volume of aerosol. These results suggest that the discordant PC20 values obtained with the two methods are not due to differences in the dose of agonist delivered to the mouth.

Ceftazidima/avibactam frente a otros antimicrobianos para el tratamiento de bacteriemias por Enterobacterales productores de carbapenemasa KPC: datos de la vida real en un hospital universitario de Argentina / Ceftazidime/avibactam versus other antibiotics for the treatment of KPC carbapenemase-producing Enterobacterales bacteremia: real-life data from a university hospital in Argentina

INTRODUCCIÓN: Las bacteriemias por Enterobacterales productores de carbapenemasa KPC (EPC-KPC) presentan una mortalidad elevada y opciones terapéuticas limitadas. OBJETIVOS: Describir y comparar la evolución de los pacientes con bacteriemia por EPC-KPC tratados con ceftazidima/avibactam (CA) frente a otros antimicrobianos (OA). PACIENTES Y MÉTODOS: Estudio prospectivo y retrospectivo de casos y controles. Se incluyeron pacientes adultos con bacteriemia por EPC-KPC, con una proporción entre casos tratados con CA y controles tratados con OA. de 1:2. Se analizaron variables clínicas, epidemiológicas y de evolución. RESULTADOS: Se incluyeron 48 pacientes (16 CA y 32 OA). Los casos se encontraban más frecuentemente neutropénicos (50 vs.16%, p = 0,012); asimismo, presentaron medianas de score de APACHE II más altas y de score de Pitt más bajas. El 65% de la cohorte total presentó un foco clínico y Klebsiellapneumoniae fue el microorganismo más frecuentemente aislado. Los casos recibieron una mayor proporción de tratamiento antimicrobiano empírico adecuado (81 vs. 53%, p = 0,05). La antibioterapia dirigida en casos y controles fue combinada en 38 y 91%, p = 0,009. Los casos presentaron menor mortalidad al día 7 y al día 30 relacionada a infección (0 vs. 22%, p = 0,04 y 0 vs. 34%, p = 0,008). Solo los controles desarrollaron shock, ingresaron a la unidad de cuidados intensivos y presentaron bacteriemia de brecha. CONCLUSIÓN: CA mostró beneficio clínico frente a OA para el tratamiento de pacientes con bacteriemia por EPC-KPC.

BACKGROUND: KPC-producing Enterobacterales bacteremia (KPCCPE) is associated with a high mortality rate and limited therapeutic options. AIM: To describe and compare the outcome of patients with KPC-CPE bacteremia treated with ceftazidime/avibactam (CA) versus other antibiotics (OA). METHODS: Prospective and retrospective cases and control study performed in adult patients with KPC-CPE bacteremia, with a 1:2 ratio between cases treated with CA. and controls treated with OA. Clinical, epidemiological, and outcome variables were analyzed. RESULTS: Forty-eight patients (16 CA and 32 OA) were included. Cases were more frequently neutropenic (50 vs. 16%, p = 0.012), presented higher median APACHE II score and lower Pitt score. Of the total cohort, 65% had a clinical source, and Klebsiella pneumoniae was the most frequently isolated microorganism. Cases received more adequate empirical antibiotic treatment (81 vs. 53%, p = 0.05). Targeted antibiotic therapy in cases and controls was combined in 38 and 91%, p = 0.009. Cases had a lower 7-day mortality and 30-day infection-related mortality (0 vs. 22%, p = 0.04 and 0 vs. 34%, p = 0.008). Only controls developed shock, were admitted to the intensive care unit, and had breakthrough bacteremia. CONCLUSION: CA. showed clinical benefit over OA in the treatment of patients with EPC-KPC bacteremia.

Prevention, control, and elimination of neglected diseases in the Americas: pathways to integrated, inter-programmatic, inter-sectoral action for health and development.

BACKGROUND: In the Latin America and Caribbean region over 210 million people live below the poverty line. These impoverished and marginalized populations are heavily burdened with neglected communicable diseases. These diseases continue to enact a toll, not only on families and communities, but on the economically constrained countries themselves. DISCUSSION: As national public health priorities, neglected communicable diseases typically maintain a low profile and are often left out when public health agendas are formulated. While many of the neglected diseases do not directly cause high rates of mortality, they contribute to an enormous rate of morbidity and a drastic reduction in income for the most poverty-stricken families and communities. The persistence of this "vicious cycle" between poverty and poor health demonstrates the importance of linking the activities of the health sector with those of other sectors such as education, housing, water and sanitation, labor, public works, transportation, agriculture, industry, and economic development. SUMMARY: The purpose of this paper is three fold. First, it focuses on a need for integrated "pro-poor" approaches and policies to be developed in order to more adequately address the multi-faceted nature of neglected diseases. This represents a move away from traditional disease-centered approaches to a holistic approach that looks at the overarching causes and mechanisms that influence the health and well being of communities. The second objective of the paper outlines the need for a specific strategy for addressing these diseases and offers several programmatic entry points in the context of broad public health measures involving multiple sectors. Finally, the paper presents several current Pan American Health Organization and other institutional initiatives that already document the importance of integrated, inter-programmatic, and inter-sectoral approaches. They provide the framework for a renewed effort toward the efficient use of resources and the development of a comprehensive integrated solution to neglected communicable diseases found in the context of poverty, and tailored to the needs of local communities.

The effect of challenge method on sensitivity and reactivity to adenosine 5'-monophosphate in subjects with suspected asthma.

BACKGROUND: The following two methods of inhalation challenge have been used to determine the airway responsiveness: the tidal-breathing method; and the dosimeter method. The objective of the study was to determine the influence of the challenge method on the response to adenosine 5'-monophosphate (AMP). METHODS: This study measured airway responsiveness to AMP by dosimeter and tidal-breathing methods in 25 subjects with suspected asthma. The two AMP challenges were conducted in random order, on separate days, at the same time of day, at intervals of 1 to 5 days. Concentration-response curves were characterized by the provocative concentration of a substance causing a 20% fall in FEV1 (PC20) and slope. RESULTS: The dosimeter PC20 values were significantly higher than the tidal-breathing PC20 values, with geometric mean (95% confidence interval [CI]) values of 50.35 mg/mL (95% CI, 19.50 to 129.72 mg/mL) and 28.97 mg/mL (95% CI, 11.99 to 69.98 mg/mL; p = 0.02), respectively. The mean difference in the PC20 values obtained with each method was 0.80 doubling concentrations (95% CI, 0.16 to 1.44 doubling concentrations). The mean values for the slope were 17.0%/log mg/mL (95% CI, 12.5 to 21.5 mg/mL) with the tidal breathing method and 13.8%/log mg/mL (95% CI, 9.0 to 18.7 mg/mL; p = 0.03) with the dosimeter. CONCLUSIONS: The tidal-breathing method produces AMP PC20 values that are significantly lower than the dosimeter method and slope values that are significantly higher than the dosimeter method. These data suggest that the results obtained with each method of testing may not be comparable.

Infección por SARS-COV-2 en pacientes con neoplasias hematológicas y trasplantes / SARS-COV-2 infection in patients with hematological malignancies and transplants

Resumen La infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y trasplantes de células progenitoras hematopoyéticas (TCPH) puede ser grave y con importante mortalidad. Llevamos a cabo un estudio prospectivo y observacional que tuvo como objetivo describir las características clínicas, epide miológicas y la evolución de la infección por SARS-CoV-2 en pacientes con neoplasias hematológicas y TCPH. Se incluyeron 20 pacientes adultos con una mediana de edad de 58 años y una mediana de score de Charlson de 3. Las infecciones fueron de adquisición comunitaria y nosocomial en el 60% y 40% respectivamente, y el 30% de los pacientes tenía antecedente de contacto con una persona infectada por SARS-CoV-2. El 65% pre sentó infiltrados pulmonares, mayormente con patrón de vidrio esmerilado en la tomografía computarizada de tórax. Casi la mitad de los pacientes tuvo enfermedad grave y crítica, y una alta proporción recibió plasma de convalecientes como tratamiento. Presentaron complicaciones e infecciones hospitalarias el 20% y 15% respec tivamente, y tuvieron una mediana de días de internación prolongada. La mortalidad a 30 días fue del 10%. La infección por SARS-CoV-2 en nuestra población tuvo considerable impacto clínico y epidemiológico.

Abstract. SARS-CoV-2 infection in patients with hematological malignancies and hematopoietic stem cell transplants (HSCT) can be severe and with significant mortality. We carried out a prospective and observational study to describe the clinical and epidemiological characteristics and outcome of SARS-CoV-2 infection in patients with hematological malignancies and HSCT. Twenty adult patients were included with a median age of 58 years and a median Charlson score of 3. Infections were community-acquired and nosocomial in 60% and 40%, respectively, and 30% of the patients had a history of contact with a SARS-CoV-2 infected person. Sixty-five percent had pulmonary infiltrates, mostly with a ground-glass pattern on CT scan. Almost half of the patients had a severe and critical illness, and a high proportion received convalescent plasma as treatment. Twenty percent and 15% had complications and hospital infections, respectively, and had prolonged hospitalization expressed as median days of it. The 30-day mortality was 10%. SARS-CoV-2 infection in our population had a considerable clinical and epidemiological impact.

Impacto clínico y epidemiológico de la infección por SARS-CoV-2 en pacientes adultos con tumores sólidos / Clinical and epidemiological impact of SARS-CoV-2 infection in adult patients with solid tumors

La infección por SARS-CoV-2 en pacientes con cáncer puede ser severa y con importante mortalidad. Diseñamos un estudio prospectivo observacional que tuvo como objetivo describir el impacto clínico y epidemiológico de la infección por SARS-CoV-2 en pacientes con tumores sólidos. Se incluyeron 27 pacientes con neoplasias activas, con una mediana de edad de 72 años, y mediana de score de Charlson de 6. Las infecciones fueron de adquisición nosocomial en 18,5% de los pacientes, y el 74% tuvo infiltrados pulmonares, con una alta proporción de patrón mixto y consolidativo en imágenes. Casi la mitad de los pacientes tuvo enfermedad severa y crítica. Presentaron complicaciones e infecciones hospitalarias el 26% y 14,8% respectivamente. La mortalidad a 30 días fue de 25,9%, mayormente relacionada al COVID-19. La infección por SARS-CoV-2 en nuestra población tuvo considerable impacto clínico y epidemiológico

SARS-CoV-2 infection in cancer patients can be severe, and with significant mortality. We performed a prospective observational study to describe the clinical and epidemiological impact of SARS-CoV-2 infection in solid tumors patients. Twenty-seven patients with active neoplasms were included, with a median age of 72 and a median Charlson score of 6. Infections were nosocomially acquired in 18.5% of the patients, and 74% had pulmonary infiltrates, with a high proportion of mixed and consolidative pattern in images. Almost half of the patients had a severe and critical illness. Twenty-six percent and 14.8% had complications and hospital infections, respectively. The 30-day mortality was 25.9%, mostly related to COVID-19. SARS-CoV-2 infection in our population had a considerable clinical and epidemiological impacto