High and very high risk of osteoporotic fracture in Colombia, 2003-2022: identifying diagnostic and treatment gaps.

This study examined the clinical characteristics and refracture rates of Colombian patients with high- and very high-risk osteoporosis. This reveals osteoporosis diagnoses and treatment gaps. Only 5.3% of the patients were diagnosed with osteoporosis at discharge and 70.5% had refractures. This finding underscores the need for national policies to enhance osteoporosis prevention and treatment. PURPOSE: This study aimed to assess the clinical features and refracture rates among patients with high- and very-high-risk osteoporosis in Colombia, highlighting diagnostic and treatment gaps. METHODS: A retrospective observational study was conducted using the medical records of patients aged ≥ 50 years who experienced fragility fractures between 2003 and 2022. Clinical and demographic characteristics at the time of the initial fracture were analyzed, as well as the subsequent imminent risk (refracture rate) and the diagnosis and treatment gap. RESULTS: 303.982 fragility fractures occurred, and only 5.3% of patients were diagnosed with osteoporosis upon discharge. The most prevalent index fractures were forearm, vertebral, rib, and hip. Only 17.8% of the cohort had a matched osteoporosis diagnosis, indicating a low healthcare capture. Among the diagnosed patients, 10.08% were classified as high- and very high-risk of fracture, predominantly women with a mean age of 73 years. Comorbidities included diabetes, Sjögren's syndrome, and heart failure. The prevalence of osteoporosis has increased significantly from 2004 to 2022, possibly due to improved detection methods, an aging population, or a combination of both. Despite this increase, treatment delay was evident. Refractures affected 70.5% of the patients, with forearm, hip, humerus, and vertebral fractures being the most common, with a mean time of refracture of 7 months. CONCLUSION: Significant delays were observed in the diagnosis and treatment of fragility fractures. Colombia's government and health system must address osteoporosis by implementing national policies that prioritize osteoporosis and fragility fracture prevention and reduce delays in diagnosis and treatment.

First report of KPC variants conferring ceftazidime-avibactam resistance in Colombia: introducing KPC-197.

Resistance to ceftazidime-avibactam (CZA) due to Klebsiella pneumoniae carbapenemase (KPC) variants is increasing worldwide. We characterized two CZA-resistant clinical Klebsiella pneumoniae strains by antimicrobial susceptibility test, conjugation assays, and WGS. Isolates belonged to ST258 and ST45, and produced a KPC-31 and a novel variant KPC-197, respectively. The novel KPC variant presents a deletion of two amino acids on the Ω-loop (del_168-169_EL) and an insertion of two amino acids in position 274 (Ins_274_DS). Continued surveillance of KPC variants conferring CZA resistance in Colombia is warranted. IMPORTANCE: Latin America and the Caribbean is an endemic region for carbapenemases. Increasingly high rates of Klebsiella pneumoniae carbapenemase (KPC) have established ceftazidime-avibactam (CZA) as an essential antimicrobial for the treatment of infections due to MDR Gram-negative pathogens. Although other countries in the region have reported the emergence of CZA-resistant KPC variants, this is the first description of such enzymes in Colombia. This finding warrants active surveillance, as dissemination of these variants could have devastating public health consequences.

A Rare Case of Single-Organ Vasculitis of the Hepatic Artery in a Female Patient: Diagnosis and Management Challenges.

This case report describes a rare occurrence of isolated vasculitis of the hepatic artery in a female patient. The patient presented with abdominal pain, fever, and weight loss, and a diagnosis was made through a combination of imaging studies and serological evaluation of systemic vasculitis. The management of this case was challenging because of the involvement of the hepatic artery without any other clinical manifestations of the systemic disease, apart from the presence of rheumatoid factor and anti-citrullinated cyclic peptide. The authors highlight the importance of considering vasculitis as a potential diagnosis in patients with unexplained abdominal pain and fever and the need for a multidisciplinary approach to the management of these patients. This case also emphasizes the potential complications of vasculitis, including aneurysm formation, and the need for close monitoring and follow-up of these patients.

Update of antimicrobial resistance in level III and IV health institutions in Colombia between January 2018 and December 2021 / Actualización sobre la resistencia antimicrobiana en instituciones de salud de nivel III y IV en Colombia entre enero del 2018 y diciembre del 2021

Introduction: Antimicrobial resistance surveillance is a fundamental tool for the development, improvement, and adjustment of antimicrobial stewardship programs, therapeutic guidelines, and universal precautions to limit the cross-transmission of resistant bacteria between patients. Since the beginning of 2020, the SARS-CoV-2 pandemic profoundly challenged the health system and, according to some reports, increased the rates of antimicrobial resistance. Objective: To describe the behavior of antimicrobial resistance of the most frequent bacterial pathogens in twenty Colombian hospitals from January 2018 to December 2021. Materials and methods: We conducted a descriptive study based on the microbiological information recorded from January 2018 to December 2021 in twenty levels III and IV health institutions in twelve Colombian cities. We identified the species of the ten most frequent bacteria along with their resistance profile to the antibiotic markers after analyzing the data through WHONET. Results: We found no statistically significant changes in most pathogens' resistance profiles from January 2018 to December 2021. Only Pseudomonas aeruginosa had a statistically significant increase in its resistance profile, particularly to piperacillin/tazobactam and carbapenems. Conclusions: The changes in antimicrobial resistance in these four years were not statistically significant except for P. aeruginosa to piperacillin/tazobactam and carbapenems.

Introducción: El comportamiento de la resistencia antimicrobiana es fundamental en el mejoramiento y ajuste de los programas de optimización de uso de antimicrobianos, la implementación de las guías terapéuticas y las precauciones que limitan la transmisión cruzada de bacterias resistentes entre pacientes. Desde el inicio del 2020, la pandemia del SARS-CoV-2 desafió profundamente al sistema de salud y, según algunos reportes, aumentó las tasas de resistencia antimicrobiana. OBJETIVO: Describir el comportamiento de la resistencia antimicrobiana en los microrganismos más frecuentes en veinte hospitales colombianos durante el periodo 2018-2021. Materiales y métodos: Se trata de un estudio descriptivo basado en la información microbiológica reportada por veinte instituciones de salud de nivel III y IV, entre enero de 2018 y diciembre de 2021, en doce ciudades de Colombia, las cuales hacen parte del "Grupo para el estudio de la resistencia nosocomial en Colombia", liderado por la Universidad El Bosque. La identificación de género y especie de los microorganismos más frecuentes, junto con su perfil de resistencia frente a antibióticos marcadores, se determinaron mediante el análisis de los datos vía WHONET. RESULTADOS: En general, los 10 microorganismos más frecuentes analizados a lo largo de los 4 años no presentaron cambios estadísticamente significativos en sus perfiles de resistencia durante los cuatro años del periodo evaluado, de 2018 a 2021. En contraste, Pseudomonas aeruginosa aumentó su resistencia frente a piperacilina-tazobactam y carbapenémicos, lo cual fue estadísticamente significativo. CONCLUSIONES: Los cambios en la resistencia antimicrobiana en estos años no han sido estadísticamente significativos, excepto para P. aeruginosa, bacteria que mostró un incremento en las tasas de resistencia a piperacilina-tazobactam y carbapenémicos.

Actualización sobre la resistencia antimicrobiana en instituciones de salud de nivel III y IV en Colombia entre enero del 2018 y diciembre del 2021 / Update of antimicrobial resistance in level III and IV health institutions in Colombia between January 2018 and December 2021

Introducción. El comportamiento de la resistencia antimicrobiana es fundamental en el mejoramiento y ajuste de los programas de optimización de uso de antimicrobianos, la implementación de las guías terapéuticas y las precauciones que limitan la transmisión cruzada de bacterias resistentes entre pacientes. Desde el inicio del 2020, la pandemia del SARS-CoV-2 desafió profundamente al sistema de salud y, según algunos reportes, aumentó las tasas de resistencia antimicrobiana. Objetivo. Describir el comportamiento de la resistencia antimicrobiana en los microrganismos más frecuentes en veinte hospitales colombianos durante el periodo 2018-2021. Materiales y métodos. Se trata de un estudio descriptivo basado en la información microbiológica reportada por veinte instituciones de salud de nivel III y IV, entre enero de 2018 y diciembre de 2021, en doce ciudades de Colombia, las cuales hacen parte del "Grupo para el estudio de la resistencia nosocomial en Colombia", liderado por la Universidad El Bosque. La identificación de género y especie de los microorganismos más frecuentes, junto con su perfil de resistencia frente a antibióticos marcadores, se determinaron mediante el análisis de los datos vía WHONET. Resultados. En general, los 10 microorganismos más frecuentes analizados a lo largo de los 4 años no presentaron cambios estadísticamente significativos en sus perfiles de resistencia durante los cuatro años del periodo evaluado, de 2018 a 2021. En contraste, Pseudomonas aeruginosa aumentó su resistencia frente a piperacilinatazobactam y carbapenémicos, lo cual fue estadísticamente significativo. Conclusiones. Los cambios en la resistencia antimicrobiana en estos años no han sido estadísticamente significativos, excepto para P. aeruginosa, bacteria que mostró un incremento en las tasas de resistencia a piperacilina-tazobactam y carbapenémicos.

Introduction. Antimicrobial resistance surveillance is a fundamental tool for the development, improvement, and adjustment of antimicrobial stewardship programs, therapeutic guidelines, and universal precautions to limit the cross-transmission of resistant bacteria between patients. Since the beginning of 2020, the SARS-CoV-2 pandemic profoundly challenged the health system and, according to some reports, increased the rates of antimicrobial resistance. Objective. To describe the behavior of antimicrobial resistance of the most frequent bacterial pathogens in twenty Colombian hospitals from January 2018 to December 2021. Materials and methods. We conducted a descriptive study based on the microbiological information recorded from January 2018 to December 2021 in twenty levels III and IV health institutions in twelve Colombian cities. We identified the species of the ten most frequent bacteria along with their resistance profile to the antibiotic markers after analyzing the data through WHONET. Results. We found no statistically significant changes in most pathogens' resistance profiles from January 2018 to December 2021. Only Pseudomonas aeruginosa had a statistically significant increase in its resistance profile, particularly to piperacillin/ tazobactam and carbapenems. Conclusions. The changes in antimicrobial resistance in these four years were not statistically significant except for P. aeruginosa to piperacillin/tazobactam and carbapenems.

Epithelial Dual Oxidase 2 Shapes the Mucosal Microbiome and Contributes to Inflammatory Susceptibility.

Reactive oxygen species (ROS) are highly reactive molecules formed from diatomic oxygen. They act as cellular signals, exert antibiotic activity towards invading microorganisms, but can also damage host cells. Dual oxidase 2 (DUOX2) is the main ROS-producing enzyme in the intestine, regulated by cues of the commensal microbiota and functions in pathogen defense. DUOX2 plays multiple roles in different organs and cell types, complicating the functional analysis using systemic deletion models. Here, we interrogate the precise role of epithelial DUOX2 for intestinal homeostasis and host-microbiome interactions. Conditional Duox2∆IEC mice lacking DUOX2, specifically in intestinal epithelial cells, were generated, and their intestinal mucosal immune phenotype and microbiome were analyzed. Inflammatory susceptibility was evaluated by challenging Duox2∆IEC mice in the dextran sodium sulfate (DSS) colitis model. DUOX2-microbiome interactions in humans were investigated by paired analyses of mucosal DUOX2 expression and fecal microbiome data in patients with intestinal inflammation. Under unchallenged conditions, we did not observe any obvious phenotype of Duox2∆IEC mice, although intestinal epithelial ROS production was drastically decreased, and the mucosal microbiome composition was altered. When challenged with DSS, Duox2∆IEC mice were protected from colitis, possibly by inhibiting ROS-mediated damage and fostering epithelial regenerative responses. Finally, in patients with intestinal inflammation, DUOX2 expression was increased in inflamed tissue, and high DUOX2 levels were linked to a dysbiotic microbiome. Our findings demonstrate that bidirectional DUOX2-microbiome interactions contribute to mucosal homeostasis, and their dysregulation may drive disease development, thus highlighting this axis as a therapeutic target to treat intestinal inflammation.

Antimicrobial Stewardship Programs in Latin America and the Caribbean: A Story of Perseverance, Challenges, and Goals.

Antimicrobial resistance is one of the major global health threats. Antimicrobial stewardship (AMS) has been set as a priority within international action plans to combat this issue. The region of Latin America and the Caribbean are recognized for their high antimicrobial resistance rates; nevertheless, a low number of studies describing implemented interventions for this topic have been published. This review aims to provide an overview of the status of AMS in our region, focusing on the main progress achieved and describing the different published efforts made by countries towards the implementation of antimicrobial stewardship programs (ASP). Common areas of intervention included were (a) education approaches, (b) antimicrobial guideline implementation and monitoring, (c) diagnostic stewardship, (d) technological tools: electronic clinical decision support systems in AMS, (e) pharmacy-driven protocols and collaborative practice agreements, and (f) economic impact. The search demonstrated the varied interventions implemented in diverse healthcare settings; the results accentuate their influence on antimicrobial consumption, antimicrobial resistance, clinical outcomes, and direct economic impact. The integration of multiple strategies within each hospital was highlighted as an essential key to ASP success. Even though the literature found demonstrated clear progress, there is still a special need for strengthening leadership from the top down, defining goals based on needs, and gaining support through policy and financing in LAC.

Antimicrobial stewardship programs in seven Latin American countries: facing the challenges.

BACKGROUND: Studies have shown that more than 50% of the antibiotics used in hospitals are unnecessary or inappropriate and, that antimicrobial resistance may cost up to 20 billion USD in excess medical costs each year. On the other hand, Antimicrobial Stewardship Programs (ASP) significantly reduce inappropriate antimicrobial use, emergence of antimicrobial resistance, healthcare associated infections, and costs in hospital settings. OBJECTIVE: To evaluate the development of ASP and antibiotic savings in 7 Latin American hospitals using standardized quantitative indicators in all the participating health care institutions. METHODS: An interventional study was conducted, where pre- and post- evaluations were performed using a standardized score tool adapted from the Joint Commission International accreditation standards and, the Colombian Institute of Technical Standards and Certification. We evaluated ASP from 7 Latin American hospitals between 2019 and 2020. A pre-intervention evaluation was done in each hospital to quantify the degree of development of the ASP (ASP Development score). Based on these results, tailored on-site training was implemented in each hospital, followed by a post-intervention evaluation to quantify improvement of ASP-development indicators. In addition, monetary savings in antimicrobials derived from the ASP intervention were estimated. RESULTS: In the pre-intervention evaluation, the average ASP development score for the 7 institutions was 65.8% (40-94.3%). The items with the lowest development score were those related to monitoring and communicating the ASP progress and success. For the post-intervention evaluation, 2 institutions couldn't participate due to the pressure imposed by the COVID-19 pandemic. For the remaining 5/7 hospitals, the average ASP development score was 82.3% with an increase of 12.0% when compared to the pre-intervention measurement of the same institutions (average pre-intervention score 70.3% (48.2%-94.3%) The items with a significant increase were key performance indicators, AMS education and training of the prescribers. Three of the seven (3/7) hospitals reported antibiotic monetary savings associated to the ASP intervention. CONCLUSIONS: The use of the tool described shown to be useful to evaluate specific areas of ASP-development that were lacking and tailor interventions for the participating hospitals, consequently, it helped improve ASP-development in the institutions that underwent pre- intervention and post-intervention analysis. In addition, the strategies showed monetary savings on antimicrobial costs when measured.

Efficient production of bispecific antibody by FAST-IgTM and its application to NXT007 for the treatment of hemophilia A.

Efficient production of bispecific antibodies (BsAbs) in single mammalian cells is essential for basic research and industrial manufacturing. However, preventing unwanted pairing of heavy chains (HCs) and light chains (LCs) is a challenging task. To address this, we created an engineering technology for preferential cognate HC/LC and HC/HC paring called FAST-Ig (Four-chain Assembly by electrostatic Steering Technology - Immunoglobulin), and applied it to NXT007, a BsAb for the treatment of hemophilia A. We introduced charged amino-acid substitutions at the HC/LC interface to facilitate the proper assembly for manufacturing a standard IgG-type BsAb. We generated CH1/CL interface-engineered antibody variants that achieved > 95% correct HC/LC pairing efficiency with favorable pharmacological properties and developability. Among these, we selected a design (C3) that allowed us to separate the mis-paired species with an unintended pharmacological profile using ion-exchange chromatography. Crystal structure analysis demonstrated that the C3 design did not affect the overall structure of both Fabs. To determine the final design for HCs-heterodimerization, we compared the stability of charge-based and knobs into hole-based Fc formats in acidic conditions and selected the more stable charge-based format. FAST-Ig was also applicable to stable CHO cell lines for industrial production and demonstrated robust chain pairing with different subclasses of parent BsAbs. Thus, it can be applied to a wide variety of BsAbs both preclinically and clinically.

Molecular Mechanisms of Resistance to Ceftazidime/Avibactam in Clinical Isolates of Enterobacterales and Pseudomonas aeruginosa in Latin American Hospitals.

Ceftazidime-avibactam (CZA) is the combination of a third-generation cephalosporin and a new non-ß-lactam ß-lactamase inhibitor capable of inactivating class A, C, and some D ß-lactamases. From a collection of 2,727 clinical isolates of Enterobacterales (n = 2,235) and P. aeruginosa (n = 492) that were collected between 2016 and 2017 from five Latin American countries, we investigated the molecular resistance mechanisms to CZA of 127 (18/2,235 [0.8%] Enterobacterales and 109/492 [22.1%] P. aeruginosa). First, by qPCR for the presence of genes encoding KPC, NDM, VIM, IMP, OXA-48-like, and SPM-1 carbapenemases, and second, by whole-genome sequencing (WGS). From the CZA-resistant isolates, MBL-encoding genes were detected in all 18 Enterobacterales and 42/109 P. aeruginosa isolates, explaining their resistant phenotype. Resistant isolates that yielded a negative qPCR result for any of the MBL encoding genes were subjected to WGS. The WGS analysis of the 67 remaining P. aeruginosa isolates showed mutations in genes previously associated with reduced susceptibility to CZA, such as those involved in the MexAB-OprM efflux pump and AmpC (PDC) hyperproduction, PoxB (blaOXA-50-like), FtsI (PBP3), DacB (PBP4), and OprD. The results presented here offer a snapshot of the molecular epidemiological landscape for CZA resistance before the introduction of this antibiotic into the Latin American market. Therefore, these results serve as a valuable comparison tool to trace the evolution of the resistance to CZA in this carbapenemase-endemic geographical region. IMPORTANCE In this manuscript, we determine the molecular mechanisms of ceftazidime-avibactam resistance in Enterobacterales and P. aeruginosa isolates from five Latin American countries. Our results reveal a low rate of resistance to ceftazidime-avibactam among Enterobacterales; in contrast, resistance in P. aeruginosa has proven to be more complex, as it might involve multiple known and possibly unknown resistance mechanisms.

Identification of mcr-1 Genes and Characterization of Resistance Mechanisms to Colistin in Escherichia coli Isolates from Colombian Hospitals.

We report the presence of the mcr-1 gene among 880 Escherichia coli clinical isolates collected in 13 hospitals from 12 Colombian cities between 2016 and 2019. Seven (0.8%) isolates were colistin resistant (MIC ≥ 4 µg/mL). These colistin-resistant isolates were screened for the presence of the mcr-1 gene; five carried the gene. These five isolates were subjected to whole genome sequencing (WGS) to identify additional resistomes and their ST. In addition, antimicrobial susceptibility testing revealed that all E. coli isolates carrying mcr-1 were susceptible to third generation-cephalosporin and carbapenems, except one, which carried an extended-spectrum ß-lactamase (CTX-M-55), along with the fosfomycin resistance encoding gene, fosA. WGS indicated that these isolates belonged to four distinct sequence types (ST58, ST46, ST393, and a newly described ST14315) and to phylogroups B1, A, and D. In this geographic region, the spread of mcr-1 in E. coli is low and has not been inserted into high-risk clones such as ST131, which has been present in the country longer.

Randomized Trial of Anticoagulation Strategies for Noncritically Ill Patients Hospitalized With COVID-19.

BACKGROUND: Prior studies of therapeutic-dose anticoagulation in patients with COVID-19 have reported conflicting results. OBJECTIVES: We sought to determine the safety and effectiveness of therapeutic-dose anticoagulation in noncritically ill patients with COVID-19. METHODS: Patients hospitalized with COVID-19 not requiring intensive care unit treatment were randomized to prophylactic-dose enoxaparin, therapeutic-dose enoxaparin, or therapeutic-dose apixaban. The primary outcome was the 30-day composite of all-cause mortality, requirement for intensive care unit-level of care, systemic thromboembolism, or ischemic stroke assessed in the combined therapeutic-dose groups compared with the prophylactic-dose group. RESULTS: Between August 26, 2020, and September 19, 2022, 3,398 noncritically ill patients hospitalized with COVID-19 were randomized to prophylactic-dose enoxaparin (n = 1,141), therapeutic-dose enoxaparin (n = 1,136), or therapeutic-dose apixaban (n = 1,121) at 76 centers in 10 countries. The 30-day primary outcome occurred in 13.2% of patients in the prophylactic-dose group and 11.3% of patients in the combined therapeutic-dose groups (HR: 0.85; 95% CI: 0.69-1.04; P = 0.11). All-cause mortality occurred in 7.0% of patients treated with prophylactic-dose enoxaparin and 4.9% of patients treated with therapeutic-dose anticoagulation (HR: 0.70; 95% CI: 0.52-0.93; P = 0.01), and intubation was required in 8.4% vs 6.4% of patients, respectively (HR: 0.75; 95% CI: 0.58-0.98; P = 0.03). Results were similar in the 2 therapeutic-dose groups, and major bleeding in all 3 groups was infrequent. CONCLUSIONS: Among noncritically ill patients hospitalized with COVID-19, the 30-day primary composite outcome was not significantly reduced with therapeutic-dose anticoagulation compared with prophylactic-dose anticoagulation. However, fewer patients who were treated with therapeutic-dose anticoagulation required intubation and fewer died (FREEDOM COVID [FREEDOM COVID Anticoagulation Strategy]; NCT04512079).

Methane Emission, Carbon Footprint and Productivity of Specialized Dairy Cows Supplemented with Bitter Cassava (Manihot esculenta Crantz).

The objective of this research was to determine the effect of cassava (Manihot esculenta Crantz) supplementation on enteric methane (CH4) emissions, carbon footprint, and production parameters in dairy cows. Daily concentrate supply for Jersey and Jersey * Holstein breeds was evaluated in four treatments (T): T1: 100% commercial concentrate; T2: 70% concentrate + 30% cassava leaves; T3: 70% concentrate + 30% cassava roots; and T4: 70% concentrate + 15% cassava leaves + 15% cassava root chips. Measurements of CH4 emissions were performed using the polytunnel technique. Average daily dry matter intake ranged from 7.8 to 8.5 kg dry matter (DM). Cassava leaves were characterized by a high crude protein (CP) content (171 g CP/kg DM), with 5 times more neutral detergent fiber (NDF) content than cassava root (587 vs. 108 g NDF/kg DM). Average enteric CH4 emissions per animal ranged from 194 to 234 g/d (p > 0.05). The carbon footprint was reduced by replacing 30% of the concentrate with cassava leaves and/or roots. Energy-corrected milk production was 1.15 times higher in Jersey * Holstein animals than Jersey cows (47 vs. 55 kg). Therefore, supplementation with cassava leaves and/or roots is a nutritionally and environmentally sustainable strategy.

Molecular mechanisms leading to ceftolozane/tazobactam resistance in clinical isolates of Pseudomonas aeruginosa from five Latin American countries.

Objectives: Identify molecular mechanisms responsible for the in vitro non-susceptibility to ceftolozane/tazobactam (TOL) in a group of 158 clinical isolates of Pseudomonas aeruginosa from five Latin American countries collected before the introduction of TOL into the clinical practice. Methods: Clinical isolates of P. aeruginosa (n = 504) were collected between January 2016 and October 2017 from 20 hospitals located in Argentina, Brazil, Chile, Colombia, and Mexico. Minimum inhibitory concentrations (MICs) to TOL were determined by standard broth microdilution and interpreted according to CLSI breakpoints. Initially, production of carbapenemases in TOL non-susceptible isolates was assessed by Rapidec® followed by qPCR to detect bla KPC, bla NDM-1, bla VIM, and bla IMP. Illumina® WGS was performed for isolates in which non-susceptibility to TOL was not mediated by carbapenemases. Results: A total of 158 (31.3%) isolates were non-susceptible to TOL. In 74 (46.8%) of these isolates, non-susceptibility to TOL was explained by the production of at least one carbapenemase. WGS revealed that some isolates carried ESBLs, mutated bla PDC and ampD, associated with decreased susceptibility to TOL. Conclusion: Substitutions found in PDC and carbapenemase production were the most common presumed mechanisms of resistance to TOL detected in this study. This study shows that epidemiological surveillance is warranted to monitor the emergence of novel mechanisms of resistance to TOL that might compromise its clinical utility.

Hypertrophic cardiomyopathy in a patient with secondary hypoparathyroidism: A case report.

Parathyroid hormone (PTH) has direct and indirect actions on cardiovascular cells. The effects of chronic hypoparathyroidism on cardiac morphology, function, and conduction are still unclear. Low PTH states are associated with multiple manifestations in the heart, acute or chronic. Acute hypocalcemic cardiomyopathy is a transient dilated cardiomyopathy with reduced ejection fraction and diffuse left ventricular hypokinesia. Chronic hypoparathyroidism-associated cardiomyopathy is a rare disease that may cause reduced myocardial tension, cardiac cavity enlargement, arrhythmias, and congestive heart failure. Here, we describe a 73-year-old woman with chronic hypoparathyroidism and hypocalcemia, who developed a hypertrophic cardiomyopathy, and not a dilated hypocalcemia-associated cardiomyopathy, which would be usually the case.

Comparative In Vitro Activity of Ceftolozane/Tazobactam against Clinical Isolates of Pseudomonas aeruginosa and Enterobacterales from Five Latin American Countries.

BACKGROUND: Ceftolozane/tazobactam (C/T) is a combination of an antipseudomonal oxyiminoaminothiazolyl cephalosporin with potent in vitro activity against Pseudomonas aeruginosa and tazobactam, a known ß-lactamase inhibitor. The aim of this study was to evaluate the activity of C/T against clinical isolates of P. aeruginosa and Enterobacterales collected from five Latin American countries between 2016 and 2017, before its clinical use in Latin America, and to compare it with the activity of other available broad-spectrum antimicrobial agents. METHODS: a total of 2760 clinical isolates (508 P. aeruginosa and 2252 Enterobacterales) were consecutively collected from 20 hospitals and susceptibility to C/T and comparator agents was tested and interpreted following the current guidelines. RESULTS: according to the CLSI breakpoints, 68.1% (346/508) of P. aeruginosa and 83.9% (1889/2252) of Enterobacterales isolates were susceptible to C/T. Overall, C/T demonstrated higher in vitro activity than currently available cephalosporins, piperacillin/tazobactam and carbapenems when tested against P. aeruginosa, and its performance in vitro was comparable to fosfomycin. When tested against Enterobacterales, it showed higher activity than cephalosporins and piperacillin/tazobactam, and similar activity to ertapenem. CONCLUSIONS: these results show that C/T is an active ß-lactam agent against clinical isolates of P. aeruginosa and Enterobacterales.

Mitochondrial Function and Microbial Metabolites as Central Regulators of Intestinal Immune Responses and Cancer.

Energy and anabolic metabolism are essential for normal cellular homeostasis but also play an important role in regulating immune responses and cancer development as active immune and cancer cells show an altered metabolic profile. Mitochondria take a prominent position in these metabolic reactions. First, most key energetic reactions take place within or in conjunction with mitochondria. Second, mitochondria react to internal cues from within the cell but also to external cues originating from the microbiota, a vast diversity of associated microorganisms. The impact of the microbiota on host physiology has been largely investigated in the last decade revealing that the microbiota contributes to the extraction of calories from the diet, energy metabolism, maturation of the immune system and cellular differentiation. Thus, changes in the microbiota termed dysbiosis have been associated with disease development including metabolic diseases, inflammation and cancer. Targeting the microbiota to modulate interactions with the mitochondria and cellular metabolism to delay or inhibit disease development and pathogenesis appears an attractive therapeutic approach. Here, we summarize recent advances in developing the therapeutic potential of microbiota-mitochondria interactions for inflammation and cancer.

Sentido Comunitario de la Coherencia en asentamientos informales: aprendizajes y reflexiones desde Medellín (Colombia) / Community Sense of Coherence in slums: learnings and reflections from Medellín (Colombia) / Sentido comunitário da coerência em assentamentos informais: aprendizagens e reflexão desde Medellín (Colômbia)

Resumen Introducción: el modelo de urbanización ha provocado un aumento de las inequidades sociales, transgrediendo los principios éticos de la justicia social y espacial. La Organización Mundial de la Salud ha identificado la urbanización como uno de los principales desafíos de salud pública del siglo XXI. Objetivo: comprender el sentido de la coherencia comunitario generado a través de los activos comunitarios para la salud en el asentamiento informal El Faro al nororiente de la ciudad de Medellín. Materiales y métodos: se realizó una investigación bajo una metodología de estudio de caso de alcance interpretativo, y un análisis narrativo de construcción de la explicación a partir de siete entrevistas semiestructuradas, dos talleres de fotovoz y un mapeo de activos comunitarios para la salud desarrollado entre 26 habitantes de Medellín. Resultados: desde el modelo salutogénico se reconoció el empoderamiento de la comunidad, porque les ha permitido enfrentar las resistencias del contexto, creando prácticas positivas y saludables. Estas prácticas han movilizado sus activos comunitarios, permitiendo el desarrollo de un importante Sentido Comunitario de la Coherencia, con el cual la comunidad enfrenta los desafíos de la vida y construye experiencias coherentes. Conclusiones: los habitantes han buscado encontrar soluciones que respondan a la situación de pobreza, en un proceso de abajo hacia arriba que ha buscado crear espacios significativos, un mayor sentido de pertenencia y una percepción de seguridad de habitar este territorio. Finalmente, cuanto mejor se conoce el entorno, mejor se conocen las comunidades entre sí y se preserva mejor la salud comunitaria y el bienestar social.

Abstract Introduction: The urbanization model has caused an increase in social inequities, transgressing the ethical principles of social and spatial justice. The World Health Organization has identified urbanization as one of the major public health challenges of the 21st century. Objective: To understand the Sense of Community Coherence generated through community assets for health in the informal settlement El Faro in the northeast of the city of Medellin. Materials and methods: This research was conducted under a case study methodology with an interpretive scope, and a narrative analysis of construction of the explanation from seven semi-structured interviews, two photo-voice workshops and a mapping of community assets for health developed between 26 inhabitants of Medellin. Results: From the salutogenic model, the empowerment of the community was recognized because it has allowed them to face the resistance of the context creating positive and healthy practices. These practices have mobilized their community assets, allowing the development of an important Community Sense of Coherence with which the community faces the challenges of life and builds coherent experiences. Conclusions: The inhabitants have sought to find solutions that respond to the situation of poverty in a bottom-up process that has search to create significant spaces, a greater sense of belonging and a perception of security in inhabiting this territory. Finally, the better the environment is known, the better the communities know each other and the better the community health and social well-being are preserved.

Resumo Introdução: o modelo de urbanização tem provocado um aumento das inequidades sociais, transgredindo os princípios éticos da justiça social e espacial. A Organização Mundial da Saúde já identificou a urbanização como um dos principais desafios da saúde pública do século XXI. Objetivo: compreender o sentido da coerência comunitária gerada a través dos ativos comunitários para a saúde no assentamento informal O Faro ao nordeste da cidade de Medellín. Materiais e métodos: realizou-se uma pesquisa baixo uma metodologia de estudo de caso de alcance interpretativo, e uma análise narrativa de construção da explicação a partir de sete entrevistas semi-estruturadas, das oficinas de foto voz e um mapeio de ativos comunitários para a saúde desenvolvendo entre 26 habitantes de Medellín. Resultados: desde o modelo salutogênico se reconheceu o empoderamento da comunidade, porque lhes permitiu enfrentar as resistências do contexto, criando práticas positivas e saudáveis. Estas práticas tem mobilizado seus ativos comunitários, permitindo o desenvolvimento de um importante Sentido Comunitário da Coerência, com o qual a comunidade enfrenta os desafios da vida e constrói experiencias coerentes. Conclusões: os habitantes procuraram encontrar soluções que respondam à situação de pobreza, em um processo de abaixo para arriba que tem buscado criar espaços significativos, um maior sentido de pertinência e uma percepção de segurança de habitar este território. Finalmente, quanto melhor se conhece o entorno, melhor se conhecem as comunidades entre si e se preserva melhor a saúde comunitária e o bem-estar social.

Bilateral striopallidal calcinosis secondary to systemic lupus erythematosus.

Bilateral symmetric striatopallidal calcinosis with or without deposits in dentate nucleus, thalamus, and white matter is reported in patients ranging from asymptomatic, metabolic, toxic, and genetic autosomal dominant, familial or sporadic forms. Of the connective tissue diseases, it has been reported in very few cases in patients with systemic lupus erythematosus, many incorrectly labeled as Fahr syndrome without even having hypoparathyroidism. Here we describe a 30-year-old female patient with neuropsychiatric systemic lupus erythematosus manifested at diagnosis with mood disorders and anxiety, and 1-year later develops Lupus headache; Incidentally, an aneurism of the right middle cerebral artery and bilateral and symmetric calcifications of the caudate and lenticular nuclei were noted; this finding is a rarely reported manifestation of neuropsychiatric systemic lupus erythematosus. A review of the literature based on this case was carried out in electronic databases. There are approximately 29 patients reported in the literature, with calcifications in the basal ganglia associated with systemic lupus erythematosus occurs almost exclusively in young women (96.5%) with a mean age of 33.36 years (2 months-76 years), with a race predilection for Asians (65.5%). Regarding the neuropsychiatric syndromes defined by the American College of Rheumatology, the most frequently associated are movement disorders; followed by cognitive dysfunction, seizure disorders, mood disorders, cerebrovascular disease, psychosis, and acute confusional state, transverse myelitis, and demyelinating syndrome. The mean duration time of the SLE to detection of the basal ganglia calcification is 7.62 years (3 days-31 years).

Analysis of Specific Physical Fitness in High-Level Table Tennis Players-Sex Differences.

Table tennis performance depends on multiple factors such as technique, tactics and fitness. Several studies have focused on investigating different technical-tactical variables. However, research analysing the specific physical qualities of this sport is scarce, particularly in the female sex. The aim of the present study was to assess the physical fitness variables associated with individual performance in elite table tennis players according to sex. Forty-eight elite players divided into males (n = 24; 25.38 ± 4.01 years) and females (n = 24; 22.33 ± 3.83 years) participated in the study. To determine physical fitness, participants performed vertical jump, hand grip strength, ergospirometry and lateral displacement tests (reaction time, displacement time and lateral acceleration). Male players showed higher values in vertical jump, hand grip strength and maximum oxygen consumption (p < 0.001). Likewise, male players moved laterally faster (p < 0.001). On the other hand, female players had a better reaction time towards the dominant side (p < 0.01). Elite male table tennis players showed better physical fitness compared to female players. Due to the scarcity of data on elite table tennis players, these results can serve as reference values for different table tennis practitioners.