An Emergent Change in Epidemiologic and Microbiological Characteristics of Bloodstream Infections in Adults With Febrile Neutropenia Resulting From Chemotherapy for Acute Leukemia and Lymphoma at Reference Centers in Chile, Ecuador, and Peru.

Background: Febrile neutropenia is a life-threatening condition commonly observed in patients with hematologic malignancies. The aim of this article is to provide updated knowledge about bloodstream infections in febrile neutropenia episodes within the Andean region of Latin America. Method: This retrospective study was based in 6 hospitals in Chile, Ecuador, and Peru and included adult patients with acute leukemia or lymphoma and febrile neutropenia between January 2019 and December 2020. Results: Of the 416 febrile neutropenia episodes, 38.7% had a bloodstream infection, 86% of which were caused by gram-negative rods, with Klebsiella pneumoniae, Escherichia coli, and Pseudomonas aeruginosa being the most frequently identified bacteria. K pneumoniae isolates were more frequently resistant than E coli to cefotaxime (65% vs 39.6%), piperacillin-tazobactam (56.7% vs 27.1%), and imipenem (35% vs 2.1%) and were more frequently multidrug resistant (61.7% vs 12.5%). Among P aeruginosa, 26.7% were resistant to ceftazidime, piperacillin-tazobactam, and imipenem, and 23.3% were multidrug resistant. Overall 30-day mortality was 19.8%, being higher with vs without a bloodstream infection (26.7% vs 15.3%, P = .005). Fever duration was also significantly longer, as well as periods of neutropenia and length of hospital stay for patients with bloodstream infection. Additionally, the 30-day mortality rate was higher for episodes with inappropriate vs appropriate empirical antibiotic therapy (41.2% vs 26.6%, P = .139). Conclusions: Considering the high rates of bacteria-resistant infection and 30-day mortality, it is imperative to establish strategies that reduce the frequency of bloodstream infections, increasing early identification of patients at higher risks of multidrug bacteria resistance, and updating existing empirical antibiotic recommendations.

A Kinase Interacting Protein 1 regulates mitochondrial protein levels in energy metabolism and promotes mitochondrial turnover after exercise.

A Kinase Interacting Protein 1 (AKIP1) is a signalling adaptor that promotes mitochondrial respiration and attenuates mitochondrial oxidative stress in cultured cardiomyocytes. We sought to determine whether AKIP1 influences mitochondrial function and the mitochondrial adaptation in response to exercise in vivo. We assessed mitochondrial respiratory capacity, as well as electron microscopy and mitochondrial targeted-proteomics in hearts from mice with cardiomyocyte-specific overexpression of AKIP1 (AKIP1-TG) and their wild type (WT) littermates. These parameters were also assessed after four weeks of voluntary wheel running. In contrast to our previous in vitro study, respiratory capacity measured as state 3 respiration on palmitoyl carnitine was significantly lower in AKIP1-TG compared to WT mice, whereas state 3 respiration on pyruvate remained unaltered. Similar findings were observed for maximal respiration, after addition of FCCP. Mitochondrial DNA damage and oxidative stress markers were not elevated in AKIP1-TG mice and gross mitochondrial morphology was similar. Mitochondrial targeted-proteomics did reveal reductions in mitochondrial proteins involved in energy metabolism. Exercise performance was comparable between genotypes, whereas exercise-induced cardiac hypertrophy was significantly increased in AKIP1-TG mice. After exercise, mitochondrial state 3 respiration on pyruvate substrates was significantly lower in AKIP1-TG compared with WT mice, while respiration on palmitoyl carnitine was not further decreased. This was associated with increased mitochondrial fission on electron microscopy, and the activation of pathways associated with mitochondrial fission and mitophagy. This study suggests that AKIP1 regulates the mitochondrial proteome involved in energy metabolism and promotes mitochondrial turnover after exercise. Future studies are required to unravel the mechanistic underpinnings and whether the mitochondrial changes are required for the AKIP1-induced physiological cardiac growth.

The role of seasonality in shaping the interactions of honeybees with other taxa.

The Eltonian niche of a species is defined as its set of interactions with other taxa. How this set varies with biotic, abiotic and human influences is a core question of modern ecology. In seasonal environments, the realized Eltonian niche is likely to vary due to periodic changes in the occurrence and abundance of interaction partners and changes in species behavior and preferences. Also, human management decisions may leave strong imprints on species interactions. To compare the impact of seasonality to that of management effects, honeybees provide an excellent model system. Based on DNA traces of interaction partners archived in honey, we can infer honeybee interactions with floral resources and microbes in the surrounding habitats, their hives, and themselves. Here, we resolved seasonal and management-based impacts on honeybee interactions by sampling beehives repeatedly during the honey-storing period of honeybees in Finland. We then use a genome-skimming approach to identify the taxonomic contents of the DNA in the samples. To compare the effects of the season to the effects of location, management, and the colony itself in shaping honeybee interactions, we used joint species distribution modeling. We found that honeybee interactions with other taxa varied greatly among taxonomic and functional groups. Against a backdrop of wide variation in the interactions documented in the DNA content of honey from bees from different hives, regions, and beekeepers, the imprint of the season remained relatively small. Overall, a honey-based approach offers unique insights into seasonal variation in the identity and abundance of interaction partners among honeybees. During the summer, the availability and use of different interaction partners changed substantially, but hive- and taxon-specific patterns were largely idiosyncratic as modified by hive management. Thus, the beekeeper and colony identity are as important determinants of the honeybee's realized Eltonian niche as is seasonality.

Little directional change in the timing of Arctic spring phenology over the past 25 years.

With the global change in climate, the Arctic has been pinpointed as the region experiencing the fastest rates of change. As a result, Arctic biological responses-such as shifts in phenology-are expected to outpace those at lower latitudes. 15 years ago, a decade-long dataset from Zackenberg in High Arctic Greenland revealed rapid rates of phenological change.1 To explore how the timing of spring phenology has developed since, we revisit the Zackenberg time series on flowering plants, arthropods, and birds. Drawing on the full 25-year period of 1996-2020, we find little directional change in the timing of events despite ongoing climatic change. We attribute this finding to a shift in the temporal patterns of climate conditions, from previous directional change to current high inter-annual variability. Additionally, some taxa appear to have reached the limits of their phenological responses, resulting in a leveling off in their phenological responses in warm years. Our findings demonstrate the importance of long-term monitoring of taxa from across trophic levels within the community, allowing for detecting shifts in sensitivities and responses and thus for updated inference in the light of added information.

A Kinase Interacting Protein 1 (AKIP1) promotes cardiomyocyte elongation and physiological cardiac remodelling.

A Kinase Interacting Protein 1 (AKIP1) is a signalling adaptor that promotes physiological hypertrophy in vitro. The purpose of this study is to determine if AKIP1 promotes physiological cardiomyocyte hypertrophy in vivo. Therefore, adult male mice with cardiomyocyte-specific overexpression of AKIP1 (AKIP1-TG) and wild type (WT) littermates were caged individually for four weeks in the presence or absence of a running wheel. Exercise performance, heart weight to tibia length (HW/TL), MRI, histology, and left ventricular (LV) molecular markers were evaluated. While exercise parameters were comparable between genotypes, exercise-induced cardiac hypertrophy was augmented in AKIP1-TG vs. WT mice as evidenced by an increase in HW/TL by weighing scale and in LV mass on MRI. AKIP1-induced hypertrophy was predominantly determined by an increase in cardiomyocyte length, which was associated with reductions in p90 ribosomal S6 kinase 3 (RSK3), increments of phosphatase 2A catalytic subunit (PP2Ac) and dephosphorylation of serum response factor (SRF). With electron microscopy, we detected clusters of AKIP1 protein in the cardiomyocyte nucleus, which can potentially influence signalosome formation and predispose a switch in transcription upon exercise. Mechanistically, AKIP1 promoted exercise-induced activation of protein kinase B (Akt), downregulation of CCAAT Enhancer Binding Protein Beta (C/EBPß) and de-repression of Cbp/p300 interacting transactivator with Glu/Asp rich carboxy-terminal domain 4 (CITED4). Concludingly, we identified AKIP1 as a novel regulator of cardiomyocyte elongation and physiological cardiac remodelling with activation of the RSK3-PP2Ac-SRF and Akt-C/EBPß-CITED4 pathway. These findings suggest that AKIP1 may serve as a nodal point for physiological reprogramming of cardiac remodelling.

Urea Reduction in Acute Kidney Injury and Mortality Risk.

INTRODUCTION: Urea is a toxin present in acute kidney injury (AKI). We hypothesize that reduction in serum urea levels might improve clinical outcomes. We examined the association between the reduction in urea and mortality. METHODS: Patients with AKI admitted to the Hospital Civil de Guadalajara were enrolled in this retrospective cohort study. We create 4 groups of urea reduction ratio (UXR) stratified by their decrease in urea from the highest index value in comparison to the value on day 10 (0%, 1-25%, 26-50%, and >50%), or at the time of death or discharge if prior to 10 days. Our primary endpoint was to observe the association between UXR and mortality. Secondary observations included determination of which types of patients achieved a UXR >50%, whether the modality of kidney replacement therapy (KRT) effected changes in UXR, and if serum creatinine (sCr) value changes were similarly associated with patient mortality. RESULTS: A total of 651 AKI patients were enrolled. The mean age was 54.1 years, and 58.6% were male. AKI 3 was present in 58.5%; the mean admission urea was 154 mg/dL. KRT was started in 32.4%, and 18.9% died. A trend toward decreased risk of death was observed in association with the magnitude of UXR. The best survival (94.3%) was observed in patients with a UXR >50%, and the highest mortality (72.1%) was observed in patients achieving a UXR of 0%. After adjusting for age, sex, diabetes mellitus, CKD, antibiotics, sepsis, hypovolemia, cardio-renal syndrome, shock, and AKI stage, the 10-day mortality was higher in groups that did not achieve a UXR of at least 25% (OR: 1.20). Patients achieving a UXR >50% were most likely initiated on dialysis due to a diagnosis of the uremic syndrome or had a diagnosis of obstructive nephropathy. Percentage change in sCr was also associated with increased mortality risk. CONCLUSIONS: In our retrospective cohort of AKI patients, the percent decrease in UXR from admission was associated with a stratified risk of death. Patients with a UXR >25% had the best associated outcomes. Overall, a greater magnitude in UXR was associated with improved patient survival.

IGF-1 boosts mitochondrial function by a Ca2+ uptake-dependent mechanism in cultured human and rat cardiomyocytes.

A physiological increase in cardiac workload results in adaptive cardiac remodeling, characterized by increased oxidative metabolism and improvements in cardiac performance. Insulin-like growth factor-1 (IGF-1) has been identified as a critical regulator of physiological cardiac growth, but its precise role in cardiometabolic adaptations to physiological stress remains unresolved. Mitochondrial calcium (Ca2+) handling has been proposed to be required for sustaining key mitochondrial dehydrogenase activity and energy production during increased workload conditions, thus ensuring the adaptive cardiac response. We hypothesized that IGF-1 enhances mitochondrial energy production through a Ca2+-dependent mechanism to ensure adaptive cardiomyocyte growth. We found that stimulation with IGF-1 resulted in increased mitochondrial Ca2+ uptake in neonatal rat ventricular myocytes and human embryonic stem cell-derived cardiomyocytes, estimated by fluorescence microscopy and indirectly by a reduction in the pyruvate dehydrogenase phosphorylation. We showed that IGF-1 modulated the expression of mitochondrial Ca2+ uniporter (MCU) complex subunits and increased the mitochondrial membrane potential; consistent with higher MCU-mediated Ca2+ transport. Finally, we showed that IGF-1 improved mitochondrial respiration through a mechanism dependent on MCU-mediated Ca2+ transport. In conclusion, IGF-1-induced mitochondrial Ca2+ uptake is required to boost oxidative metabolism during cardiomyocyte adaptive growth.

Serum Potassium Trajectory during Acute Kidney Injury and Mortality Risk.

BACKGROUND: The association between potassium (sK) level trajectory and mortality or the need for kidney replacement therapy (KRT) during acute kidney injury (AKI) has not been adequately explored. METHODS: In this prospective cohort, AKI patients admitted to the Hospital Civil de Guadalajara were enrolled. Eight groups based on the sK (mEq/L) level trajectories during 10 days of hospitalization were created (1) normokalemia (normoK), defined as sK between 3.5-5.5; (2) hyperkalemia to normoK; (3) hypokalemia to normoK; (4) fluctuating potassium; (5) persistent hypoK; (6) normoK to hypoK; (7) normoK to hyperK; (8) persistent hyperK. We assessed the association of sK trajectories with mortality and the need for KRT. RESULTS: A total of 311 AKI patients were included. The mean age was 52.6 years, and 58.6% were male. AKI stage 3 was present in 63.9%. KRT started in 36% patients, and 21.2% died. After adjusting for confounders, 10-day hospital mortality was significantly higher in groups 7 and 8 (OR, 1.35 and 1.61, p < 0.05, for both, respectively), and KRT initiation was higher only in group 8 (OR 1.38, p < 0.05) compared with group 1. Mortality in different subgroups of patients in group 8 did not change the primary results. CONCLUSION: In our prospective cohort, most patients with AKI had alterations in sK+. NormoK to hyperK and persistent hyperK were associated with death, while only persistent hyperK was correlated with the need for KRT.

Comprehensive Phenotyping in Inflammatory Bowel Disease: Search for Biomarker Algorithms in the Transkingdom Interactions Context.

Inflammatory bowel disease (IBD) is the most common form of intestinal inflammation associated with a dysregulated immune system response to the commensal microbiota in a genetically susceptible host. IBD includes ulcerative colitis (UC) and Crohn's disease (CD), both of which are remarkably heterogeneous in their clinical presentation and response to treatment. This translates into a notable diagnostic challenge, especially in underdeveloped countries where IBD is on the rise and access to diagnosis or treatment is not always accessible for chronic diseases. The present work characterized, for the first time in our region, epigenetic biomarkers and gut microbial profiles associated with UC and CD patients in the Buenos Aires Metropolitan area and revealed differences between non-IBD controls and IBD patients. General metabolic functions associated with the gut microbiota, as well as core microorganisms within groups, were also analyzed. Additionally, the gut microbiota analysis was integrated with relevant clinical, biochemical and epigenetic markers considered in the follow-up of patients with IBD, with the aim of generating more powerful diagnostic tools to discriminate phenotypes. Overall, our study provides new insights into data analysis algorithms to promote comprehensive phenotyping tools using quantitative and qualitative analysis in a transkingdom interactions network context.

Portable sauna stimulated-diaphoresis for the treatment of fluid-overload in peritoneal dialysis patients: A pilot study.

Background: Fluid overload (FO) is a common problem in patients with peritoneal dialysis (PD), it is associated with adverse outcomes and may persist despite adjustements in PD therapy. Objective: To evaluate the feasibility and safety of stimulated diaphoresis to reduce FO with the use of a portable sauna bath. Methods: Open-label pilot study in patients on continuous ambulatory peritoneal dialysis (CAPD) and FO. The primary outcome was the treatment-related adverse events; secondary outcomes were changes in over-hydration (OH), body weight and blood pressure, FO symptoms, and sleep quality. Dialysis prescription and daily data were recorded. The intervention period consisted in a 30-min, 45°C sauna bath, daily for 10 days, using a portable sauna bath. Results: Fifty-one out of 54 total sauna bath sessions were well tolerated. In three (5.5%) sessions adverse effects were reported: transient dizziness in two cases, and a second-degree skin burn in a patient with advanced diabetic neuropathy. OH (6.3 ± 1.2 L vs. 5.5 ± 1.3 L, p = 0.05), body weight (67.7 ± 11.4 vs. 66.8 ± 3.8 kg, p = 0.003), diastolic blood pressure (92 ± 13.5 vs. 83 ± 13.3 mmHg, P = 0.003) and PSQI score (7.3 ± 3.7 vs. 5.1 ± 3.2, p = 0.02) improved significantly between the control and intervention period, respectively. Conclusions: Stimulated diaphoresis with a portable sauna bath could be a novel, safe, and effective alternative way to reduce FO in CAPD patients. Larger studies are needed to confirm our results. Clinical trial registration: ClinicalTrials.gov, identifier: NCT03563898.

Discoidin domain receptor 1 regulates ErbB2/ErbB3 signaling in mammary epithelial cells.

The ErbB2 receptor tyrosine kinase plays a key role in mammary gland development. It forms large clusters which serve as signaling platforms for integration of extracellular information. The discoidin domain receptor (DDR) family are collagen receptor tyrosine kinases which, together with ErbB2, are involved in many physiological and pathological processes. Here, we investigated the interaction of ErbB2 and DDR1 receptors in breast cancer cells. In contrast to beta1-integrin, DDR1 colocalizes with ErbB2 in membrane clusters regardless of their expression levels. We demonstrated that this spatial coexistence is a consequence of the physical interaction between these receptors. In addition, these receptors are coexpressed in the normal mammary gland but not in breast tumor samples. Together, these results present DDR1 as a novel modulator of the ErbB2/ErbB3 signaling pathway.

Registro prospectivo de pacientes que presentan paro cardiorrespiratorio extrahospitalario en Santiago, Chile / A registry of out-of-hospital cardiac arrest in Chile

BACKGROUND: The rate of survival to hospital discharge is less than 10% for out-of-hospital cardiac arrest (OHCA). AIM: To develop and implement a Chilean prospective, standardized cardiac arrest registry following the Utstein criteria. MATERIAL AND METHODS: We conducted a prospective registry for patients presenting at an urban, academic, high complexity emergency department (ED) after having an OHCA. The facility serves approximately 10% of the national population. Data were registered and analyzed following the Utstein criteria for reporting OHCA. RESULTS: For three years, 289 patients aged 59 ± 19 years (63% men) were included. Fifty seven percent of patients were taken to a health care facility for the first medical assessment by relatives or witnesses and 34% was assisted and transferred by prehospital personnel. In the subgroup of non-traumatic OHCA, 28% (n = 54) received bystander cardiopulmonary resuscitation (CPR). The registered cardiac rhythms were asystole (61%), pulseless electrical activity (PEA) (25%) and ventricular tachycardia (VT) or ventricular fibrillation (VF) (11%). The overall survival rate to discharge from the hospital was 10%, while survival with mRankin score 0-1 was 5%. The median hospitalization length of stay was 18 days among those who survived, compared with five days for the group of patients that died during the hospital stay. CONCLUSIONS: OHCA is an important cause of death in Chile. The development of a national registry that follows the International Liaison Committee on Resuscitation guidelines is the first step to assess the profile of OHCA in the region. It will provide crucial information to identify prognostic factors and variables that can help develop standards of care and set up the basis to optimize cardiac arrest management within our country and region.

Could SGLT2 Inhibitors Improve Exercise Intolerance in Chronic Heart Failure?

Despite the constant improvement of therapeutical options, heart failure (HF) remains associated with high mortality and morbidity. While new developments in guideline-recommended therapies can prolong survival and postpone HF hospitalizations, impaired exercise capacity remains one of the most debilitating symptoms of HF. Exercise intolerance in HF is multifactorial in origin, as the underlying cardiovascular pathology and reactive changes in skeletal muscle composition and metabolism both contribute. Recently, sodium-related glucose transporter 2 (SGLT2) inhibitors were found to improve cardiovascular outcomes significantly. Whilst much effort has been devoted to untangling the mechanisms responsible for these cardiovascular benefits of SGLT2 inhibitors, little is known about the effect of SGLT2 inhibitors on exercise performance in HF. This review provides an overview of the pathophysiological mechanisms that are responsible for exercise intolerance in HF, elaborates on the potential SGLT2-inhibitor-mediated effects on these phenomena, and provides an up-to-date overview of existing studies on the effect of SGLT2 inhibitors on clinical outcome parameters that are relevant to the assessment of exercise capacity. Finally, current gaps in the evidence and potential future perspectives on the effects of SGLT2 inhibitors on exercise intolerance in chronic HF are discussed.

A Two-Time Point Analysis of Gut Microbiota in the General Population of Buenos Aires and Its Variation Due to Preventive and Compulsory Social Isolation During the COVID-19 Pandemic.

The COVID-19 pandemic poses a great challenge to global public health. The extraordinary daily use of household disinfectants and cleaning products, social distancing and the loss of everyday situations that allow contact between individuals, have a direct impact on the transfer of microorganisms within the population. Together, these changes, in addition to those that occur in eating habits, can affect the composition and diversity of the gut microbiota. A two-time point analysis of the fecal microbiota of 23 Metropolitan Buenos Aires (BA) inhabitants was carried out, to compare pre-pandemic data and its variation during preventive and compulsory social isolation (PCSI) in 2020. To this end, 23 healthy subjects, who were previously studied by our group in 2016, were recruited for a second time during the COVID-19 pandemic, and stool samples were collected from each subject at each time point (n = 46). The hypervariable region V3-V4 of the 16S rRNA gene was high-throughput sequenced. We found significant differences in the estimated number of observed features (p < 0.001), Shannon entropy index (p = 0.026) and in Faith phylogenetic diversity (p < 0.001) between pre-pandemic group (PPG) vs. pandemic group (PG), being significantly lower in the PG. Although no strong change was observed in the core microbiota between the groups in this study, a significant decrease was observed during PCSI in the phylum Verrucomicrobia, which contributes to intestinal health and glucose homeostasis. Microbial community structure (beta diversity) was also compared between PPG and PG. The differences observed in the microbiota structure by unweighted UniFrac PCoA could be explained by six differential abundant genera that were absent during PCSI. Furthermore, putative functional genes prediction using PICRUSt infers a smaller predicted prevalence of genes in the intestinal tryptophan, glycine-betaine, taurine, benzoate degradation, as well as in the synthesis of vitamin B12 during PCSI. This data supports the hypothesis that the microbiome of the inhabitants of BA changed in the context of isolation during PCSI. Therefore, these results could increase the knowledge necessary to propose strategic nutraceutical, functional food, probiotics or similar interventions that contribute to improving public health in the post-pandemic era.

Covidex: An ultrafast and accurate tool for SARS-CoV-2 subtyping.

The epidemiological surveillance of SARS-CoV-2 by means of whole-genome sequencing has revealed the emergence and co-existence of multiple viral lineages or subtypes throughout the world. Moreover, it has been shown that several subtypes of this virus display particular phenotypes, such as increased transmissibility or reduced susceptibility to neutralizing antibodies, leading to the denomination of Variants of Interest (VOI) or Variants of Concern (VOC). Thus, subtyping of SARS-CoV-2 is a crucial step for the surveillance of this pathogen. Here, we present Covidex, an open-source, alignment-free machine learning subtyping tool. It is a shiny web app that allows an ultra-fast and accurate classification of SARS-CoV-2 genome sequences into the three most used nomenclature systems (GISAID, Nextstrain, Pango lineages). It also categorizes input sequences as VOI or VOC, according to current definitions. The program is cross-platform compatible and it is available via Source-Forge https://sourceforge.net/projects/covidex or via the web application http://covidex.unlu.edu.ar.

The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial.

AIM: The main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF). METHODS: In a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion. RESULTS: From July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53). CONCLUSION: In patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

[A registry of out-of-hospital cardiac arrest in Chile]. / Registro prospectivo de pacientes que presentan paro cardiorrespiratorio extrahospitalario en Santiago, Chile.

BACKGROUND: The rate of survival to hospital discharge is less than 10% for out-of-hospital cardiac arrest (OHCA). AIM: To develop and implement a Chilean prospective, standardized cardiac arrest registry following the Utstein criteria. MATERIAL AND METHODS: We conducted a prospective registry for patients presenting at an urban, academic, high complexity emergency department (ED) after having an OHCA. The facility serves approximately 10% of the national population. Data were registered and analyzed following the Utstein criteria for reporting OHCA. RESULTS: For three years, 289 patients aged 59 ± 19 years (63% men) were included. Fifty seven percent of patients were taken to a health care facility for the first medical assessment by relatives or witnesses and 34% was assisted and transferred by prehospital personnel. In the subgroup of non-traumatic OHCA, 28% (n = 54) received bystander cardiopulmonary resuscitation (CPR). The registered cardiac rhythms were asystole (61%), pulseless electrical activity (PEA) (25%) and ventricular tachycardia (VT) or ventricular fibrillation (VF) (11%). The overall survival rate to discharge from the hospital was 10%, while survival with mRankin score 0-1 was 5%. The median hospitalization length of stay was 18 days among those who survived, compared with five days for the group of patients that died during the hospital stay. CONCLUSIONS: OHCA is an important cause of death in Chile. The development of a national registry that follows the International Liaison Committee on Resuscitation guidelines is the first step to assess the profile of OHCA in the region. It will provide crucial information to identify prognostic factors and variables that can help develop standards of care and set up the basis to optimize cardiac arrest management within our country and region.

Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?

Impaired exercise capacity is the key symptom of heart failure (HF) and is associated with reduced quality of life and higher mortality rates. Unfortunately, current therapies, although generally lifesaving, have only small or marginal effects on exercise capacity. Specific strategies to alleviate exercise intolerance may improve quality of life, while possibly improving prognosis as well. There is overwhelming evidence that physical exercise improves performance in cardiac and skeletal muscles in health and disease. Unravelling the mechanistic underpinnings of exercise-induced improvements in muscle function could provide targets that will allow us to boost exercise performance in HF. With the current review we discuss: (i) recently discovered signalling pathways that govern physiological muscle growth as well as mitochondrial quality control mechanisms that underlie metabolic adaptations to exercise; (ii) the mechanistic underpinnings of exercise intolerance in HF and the benefits of exercise in HF patients on molecular, functional and prognostic levels; and (iii) potential molecular therapeutics to improve exercise performance in HF. We propose that novel molecular therapies to boost adaptive muscle growth and mitochondrial quality control in HF should always be combined with some form of exercise training.

Vascular Access and Clinical Outcomes in Underserved Hemodialysis Patients in Mexico.

INTRODUCTION: Central venous catheter (CVC) as vascular access in hemodialysis (HD) associates with adverse outcomes. Early CVC to fistula or graft conversion improves these outcomes. While socioeconomic disparities between the USA and Mexico exist, little is known about CVC prevalence and conversion rates in uninsured Mexican HD patients. We examined vascular access practice patterns and their effects on survival and hospitalization rates among uninsured Mexican HD patients, in comparison with HD patients who initiated treatment in the USA. METHODS: In this retrospective study of incident HD patients at Hospital Civil (HC; Guadalajara, MX) and the Renal Research Institute (RRI; USA), we categorized patients by the vascular access at the first month of HD and after the following 6 months. Factors associated with continued CVC use were identified by a logistic regression model. We developed multivariate Cox proportional hazards models to investigate the effects of access and conversion on mortality and hospitalization over an 18-month follow-up period. RESULTS: In 1,632 patients from RRI, the CVC prevalence at month 1 was 64% and 97% among 174 HC patients. The conversion rate was 31.7% in RRI and 10.6% in HC. CVC to non-central venous catheter (NON-CVC) conversion reduced the risk of hospitalization in both HC (aHR 0.38 [95% CI: 0.21-0.68], p = 0.001) and RRI (aHR 0.84 [95% CI: 0.73-0.93], p = 0.001). NON-CVC patients had a lower mortality risk in both populations. DISCUSSION/CONCLUSION: CVC prevalence and conversion rates of CVC to NON-CVC differed between the US and Mexican patients. An association exists between vascular access type and hospitalization and mortality risk. Prospective studies are needed to evaluate if accelerated and systematic catheter use reduction would improve outcomes in these populations.