FGF23 as a Potential Pathophysiological Factor in Peripheral Arterial Disease Associated with Chronic Kidney Disease.

Fibroblast growth factor 23 (FGF23) levels are often elevated in chronic kidney disease (CKD). FGF23 and inflammation are common characteristics in CKD, and both are associated with worse disease progression and the occurrence of complications. The existence of an interaction between FGF23 and inflammation has been suggested, each of which influences the expression and activity of the other, leading to a vicious feedback loop with adverse outcomes, including cardiovascular disease and mortality. In this work, we determined circulating FGF23 levels in a group of patients with CKD stages 3 and 4 subjected to elective femoral endarterectomy due to established peripheral artery disease (PAD), a condition resulting from an athero-inflammatory process, and we studied its associations with different inflammatory markers and mediators. We evaluated its association with serum tumor necrosis factor (TNF)α, interleukin (IL) 6, and IL10, as well as with the gene expression levels of these parameters and A disintegrin and metalloproteinase domain-containing protein (ADAM) 17 in femoral vascular tissue and peripheral blood circulating cells (PBCCs). We also analyzed its association with serum concentrations of C-reactive protein (CRP), the systemic immune inflammation index (SII), and the neutrophil-to-lymphocyte ratio (NLR). Finally, we determined the vascular immunoreactivity of protein TNFα in a subgroup of patients. FGF23 concentrations were independently associated with circulating and PBCC mRNA levels of TNFα. Worst kidney function and diabetes were also found to be contributing to FGF23 levels. Patients with higher levels of FGF23 also had greater vascular immunoreactivity for TNFα.

Acute flaccid myelitis: cause, diagnosis, and management.

Acute flaccid myelitis (AFM) is a disabling, polio-like illness mainly affecting children. Outbreaks of AFM have occurred across multiple global regions since 2012, and the disease appears to be caused by non-polio enterovirus infection, posing a major public health challenge. The clinical presentation of flaccid and often profound muscle weakness (which can invoke respiratory failure and other critical complications) can mimic several other acute neurological illnesses. There is no single sensitive and specific test for AFM, and the diagnosis relies on identification of several important clinical, neuroimaging, and cerebrospinal fluid characteristics. Following the acute phase of AFM, patients typically have substantial residual disability and unique long-term rehabilitation needs. In this Review we describe the epidemiology, clinical features, course, and outcomes of AFM to help to guide diagnosis, management, and rehabilitation. Future research directions include further studies evaluating host and pathogen factors, including investigations into genetic, viral, and immunological features of affected patients, host-virus interactions, and investigations of targeted therapeutic approaches to improve the long-term outcomes in this population.

Acute Flaccid Myelitis Associated with Enterovirus D68 in Children, Argentina, 2016.

After a 2014 outbreak of severe respiratory illness caused by enterovirus D68 in the United States, sporadic cases of acute flaccid myelitis have been reported worldwide. We describe a cluster of acute flaccid myelitis cases in Argentina in 2016, adding data to the evidence of association between enterovirus D68 and this polio-like illness.

Soluble levels and endogenous vascular gene expression of KLOTHO are related to inflammation in human atherosclerotic disease.

Atherosclerosis is a chronic inflammatory disorder affecting the artery wall. Klotho, an anti-aging factor expressed in the vessel walls that participates in the maintenance of vascular homeostasis, can be down-regulated by inflammation. In this proof-of-concept work we seek to characterize the arterial KLOTHO expression in the vascular wall, as well as the serum concentration of this protein, in a group of patients with clinical atherosclerotic disease. In addition, we aim to analyze the relationship between Klotho and inflammation. Vascular samples were obtained from 27 patients with atherosclerotic disease under an elective vascular surgery procedure, and from 11 control subjects (cadaveric organ donation programme). qRT-PCR was performed to analyze the gene expression of KLOTHO, TNF-α, IL-6, and IL-10 Serum levels of soluble KLOTHO were measured by ELISA. As compared with control subjects, serum concentrations and vascular expression of Klotho were lower in patients with atherosclerotic vascular disease, whereas inflammatory status was significantly higher. There was a negative and significant correlation between inflammatory parameters and Klotho. After controlling for the effect of other variables, partial correlation showed a direct relationship between vascular KLOTHO gene expression and IL-10 mRNA levels, whereas there was a negative association with serum LDL concentrations and vascular TNF-α expression. Our study indicates an inverse interrelationship between inflammation and Klotho in atherosclerosis. Further studies are necessary to elucidate whether the inflammatory state causes Klotho deficiency or, on the contrary, reduction of Klotho could be responsible for greater inflammation, and finally, to investigate the potential clinical relevance of this association.

Clinical and cost-effectiveness analysis of early detection of patients at nutrition risk during their hospital stay through the new screening method CIPA: a study protocol.

BACKGROUND: Malnutrition is highly prevalent in hospitalized patients and results in a worsened clinical course as well as an increased length of stay, mortality, and costs. Therefore, simple nutrition screening systems, such as CIPA (control of food intake, protein, anthropometry), may be implemented to facilitate the patient's recovery process. The aim of this study is to evaluate the effectiveness and cost-effectiveness of implementing such screening tool in a tertiary hospital, consistent with the lack of similar, published studies on any hospital nutrition screening system. METHODS: The present study is carried out as an open, controlled, randomized study on patients that were admitted to the Internal Medicine and the General and Digestive Surgery ward; the patients were randomized to either a control or an intervention group (n = 824, thereof 412 patients in each of the two study arms). The control group underwent usual inpatient clinical care, while the intervention group was evaluated with the CIPA screening tool for early detection of malnutrition and treated accordingly. CIPA nutrition screening was performed upon hospital admission and classified positive when at least one of the following parameters was met: 72 h food intake control < 50%, serum albumin < 3 g/dL, body mass index < 18.5 kg/m2 (or mid-upper arm circumference ≤ 22.5 cm). In this case, the doctor decided on whether or not providing nutrition support. The following variables will be evaluated: hospital length of stay (primary endpoint), mortality, 3-month readmission, and in-hospital complications. Likewise, the quality of life questionnaires EQ-5D-5 L are being collected for all patients at hospital admission, discharge, and 3 months post-discharge. Analysis of cost-effectiveness will be performed by measuring effectiveness in terms of quality-adjusted life years (QALYs). The cost per patient will be established by identifying health care resource utilization; cost-effectiveness will be determined through the incremental cost-effectiveness ratio (ICER). We will calculate the incremental cost per QALY gained with respect to the intervention. DISCUSSION: This ongoing trial aims to evaluate the cost-effectiveness of implementing the malnutrition screening tool CIPA in a tertiary hospital. TRIAL REGISTRATION: Clinical Trial.gov ( NCT02721706 ). First receivevd: March 1, 2016 Last updated: April 8, 2017 Last verified: April 2017.

Unravelling a Direct Role for Polysaccharide ß-Strands in the Higher Order Structure of Physical Hydrogels.

The mechanical properties of agarose-derived hydrogels depend on the scaffolding of the polysaccharide network. To identify and quantify such higher order structure, we applied Raman optical activity (ROA)-a spectroscopic technique that is highly sensitive toward carbohydrates-on native agarose and chemically modified agarose in the gel phase for the first time. By spectral global fitting, we isolated features that change as a function of backbone carboxylation (28, 40, 50, 60, 80, and 93 %) from other features that remain unchanged. We assigned these spectral features by comparison to ROA spectra calculated for different oligomer models. We found a 60:40 ratio of double- and single-stranded α-helix in the highly rigid hydrogel of native agarose, while the considerably softer hydrogels made from carboxylated agarose use a scaffold of unpaired ß-strands.

[Effectiveness of commercial repellents against Aedes aegypti (L.) in Yucatan, México]. / Efectividad de repelentes comerciales disponibles contra el mosquito Aedes aegypti (L.) en Yucatán, México.

OBJECTIVE: We assessed the efficacy of commercial repellents available in Yucatan against Aedes aegypti, vector of dengue, Chikungunya and Zika. MATERIALS AND METHODS: Protection time was determined based on WHO/CTD/ WHOPES/IC y la NOM-032-SSA2-20I4. RESULTS: Products with DEET (N, N-diethyl-3-methylbenzamide) at 25% met the recommended protection. Efficacy was directly proportional to the concentration of DEET; botanicals repellents resulted no protective. CONCLUSIONS: Repellents with DEET provided more protection against Ae. aegypti and botanical repellents, including impregnated wristbands, provided no protection.

Cost-effectiveness analysis of the pediatric 20-valent pneumococcal conjugate vaccine compared with lower-valent alternatives in Argentina.

OBJECTIVES: The 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina's national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina's pediatric NIP. METHODS: A decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty. RESULTS: Compared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments. CONCLUSION: Over a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options.

Cost-Effectiveness of 20-Valent Pneumococcal Conjugate Vaccine in Argentinean Adults.

INTRODUCTION: In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23; PCV13 → PPSV23) has been recommended for all adults aged ≥ 65 years and younger adults with chronic medical ("moderate-risk") or immunocompromising ("high-risk") conditions since 2017. With the approval of a 20-valent PCV (PCV20), we evaluated the cost-effectiveness of PCV20 versus current recommendations for moderate-/high-risk adults aged 18-64 years and all adults 65-99 years. METHODS: A probabilistic cohort model was used to project lifetime outcomes and costs associated with invasive pneumococcal disease (IPD) and all-cause non-bacteremic pneumonia (NBP), and the expected impact of vaccination. Clinical outcomes were projected annually based on Argentinean data. Economic costs were estimated based on cases and corresponding medical costs (adjusted to 2023 USD) and costs of vaccine and administration. Cost-effectiveness of PCV20 was evaluated versus the current strategy, PCV13 → PPSV23, and alternatively, versus sequentially administered 15-valent PCV and PPSV23 (PCV15 → PPSV23), and presented as cost per quality-adjusted life year gained; a healthcare system perspective was used. Costs and benefits were discounted at 3%/year. RESULTS: PCV20 in lieu of PCV13 → PPSV23 among moderate-/high-risk adults aged 18-64 years and all adults 65-99 years (N = 13.4M) prevented 3838 IPD, 4377 inpatient NBP, and 6003 outpatient NBP cases, and 1865 disease-related deaths; relative to PCV15 → PPSV23 the corresponding reductions were 2775, 3285, 4518, and 1348. PCV20 was projected to be the dominant strategy versus PCV13 → PPSV23 and PCV15 → PPSV23 as overall costs were lower by $87.6M and $80.8M, respectively. In probabilistic sensitivity analyses, PCV20 was dominant (i.e., more effective, less costly) in 100% of 1000 simulations. CONCLUSIONS: Analyses suggest implementing a PCV20 vaccination program in moderate-/high-risk adults aged 18-64 years and all adults ≥ 65 years-in lieu of PCV13 → PPSV23-would yield substantial reductions in pneumococcal disease and would be cost saving to the Argentinean healthcare system.

Pneumococcal pneumonia has a high disease burden in both children and adults. Older adults and those with certain underlying conditions are more susceptible to severe pneumococcal disease resulting in considerable economic burden on the healthcare system. In Argentina, vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) a year later is recommended for all adults aged ≥ 65 years and adults aged 18­64 years with underlying risk conditions. Despite vaccination efforts, prevalence of pneumococcal disease remains high. Two higher-valent PCVs­15-valent PCV (PCV15) and 20-valent PCV (PCV20)­are available for use in adults with PCV20 offering additional serotype coverage. This study assessed the cost-effectiveness of replacing current (PCV13 → PPSV23) and alternative (PCV15 → PPSV23) vaccination strategies with PCV20 alone. The use of PCV20 was evaluated among Argentinean adults aged 18­64 years with underlying risk conditions and all adults aged 65­99 years (N = 13 million). Over a lifetime time horizon, compared to PCV13 → PPSV23, PCV20 use would avert 14,218 cases and 1865 deaths, and increase quality-adjusted life years by 8655. Compared to PCV15 → PPSV23, PCV20 reduced cases and deaths by 10,578 and 1348, respectively, and increased quality-adjusted life years by 6341. In both comparisons, PCV20 use was cost saving with $87.6 million and $80.8 million lower costs compared to PCV13 → PPSV23 and PCV15 → PPSV23, respectively. Results of the cost-effectiveness analyses suggest that the use of PCV20 is a cost-saving strategy, reducing overall costs to the healthcare system and improving public health.

Pediatric COVID-19 in Argentina: a comprehensive analysis of disease and economic burden through official data and a systematic literature review.

Background: Limited data are available on the clinical impact and economic burden of COVID-19 in the pediatric population in Argentina. We aimed to estimate the disease and economic burden of COVID-19 on children and adolescents. Methods: We analyzed official national databases and conducted a supplemental systematic review of the published literature with meta-analysis in children aged 0-18. The period of interest was from March 2020 to August 2021, before the introduction of vaccination in this age group as a national strategic plan. In addition, we used a cost of illness analysis to estimate the direct medical costs associated with COVID-19. All costs are reported in US dollars 2023. Results: A total of 450,503 confirmed COVID-19 cases and 180 multisystem inflammatory syndrome (MIS-C) were reported in Argentina in the study period. Fourteen observational clinical studies were identified. The meta-analyses of severity level from hospital patients showed that according to different studies 15%-28% of cases were asymptomatic, 68%-88% were mild or moderate, and 3%-10% were severe or critical. About 28% of children had an underlying disease. In addition, the estimated economic burden associated with COVID-19 was 80 million dollars and 4 million dollars corresponded to MISC. Conclusion: Significant impact of COVID-19 on the healthcare system and substantial economic implications for the pediatric population in Argentina were identified. The findings should help policymakers to make informed decisions and allocate resources effectively.

Narrative Review of the Evolution of COVID-19 Vaccination Recommendations in Countries in Latin America, Africa and the Middle East, and Asia.

The rapid rollout of vaccines to combat the coronavirus disease 2019 (COVID-19) pandemic over the past 2 years has resulted in the use of various vaccine platforms and regional differences in COVID-19 vaccine implementation strategies. The aim of this narrative review was to summarize evolving COVID-19 vaccine recommendations in countries in Latin America, Asia, and Africa and the Middle East across various vaccine platforms, age groups, and specific subpopulations. Nuances in primary and booster vaccination schedules were evaluated, and the preliminary impact of such diverse vaccination strategies are discussed, including key vaccine effectiveness data in the era of Omicron-lineage variants. Primary vaccination rates for included Latin American countries were 71-94% for adults and between 41% and 98% for adolescents and children; rates for first booster in adults were 36-85%. Primary vaccination rates for adults in the included Asian countries ranged from 64% in the Philippines to 98% in Malaysia, with corresponding booster rates varying from 9% in India to 78% in Singapore; for adolescents and children, primary vaccination rates ranged from 29% in the Philippines to 93% in Malaysia. Across included African and Middle Eastern countries, primary vaccination rates in adults varied widely from 32% in South Africa to 99% in the United Arab Emirates; booster rates ranged from 5% in South Africa to 60% in Bahrain. Evidence from the regions studied indicates preference of using an mRNA vaccine as a booster on the basis of safety and effectiveness of observed real-world data, especially during circulation of Omicron lineages. Vaccination against COVID-19 remains of paramount importance to reduce the burden of disease; strategies to overcome vaccine inequity, fatigue, hesitancy, and misinformation and to ensure adequate access and supply are also important.

Klotho expression in peripheral blood circulating cells is associated with vascular and systemic inflammation in atherosclerotic vascular disease.

Cardiovascular disease is the leading cause of death worldwide. New therapeutic strategies are aimed to modulate the athero-inflammatory process that partially orchestrates underlying vascular damage. Peripheral blood circulating cells include different immune cells with a central role in the development of the atherogenic inflammatory response. The anti-aging protein α-Klotho has been related to protective effects against CVD. KL is expressed in monocytes, macrophages, and lymphocytes where it exerts anti-inflammatory effects. In this work, we analyse the relationships of the levels of inflammatory markers with the expression of the KL gene in PBCCs and with the serum levels of soluble KL in atherosclerotic vascular disease. For this, we conducted a cross-sectional single-center case-control study including a study group of 76 CVD patients and a control group of 16 cadaveric organ donors without medical antecedent or study indicating CVD. Vascular artery fragments and whole blood and serum samples were obtained during elective or organ retrieval surgery. Serum levels of sKL, TNFα and IL10, and gene expression levels of KL, TNF, IL10, NFKB1, DNMT1, and DNMT3A in PBCCs were measured. In these cells, we also determined KL promoter methylation percentage. Histological and immunohistochemical analyses were employed to visualize atherosclerotic lesions and to measure IL10 and TNFα levels in vascular fragments. Patients with CVD presented higher values of proinflammatory markers both at systemic and in the vasculature and in the PBCCs, compared to the control group. In PBCCs, CVD patients also presented lower gene expression levels of KL gene (56.4% difference, P < 0.001), higher gene expression levels of DNMT1 and DNMT3A (P < 0.0001, for both) and a higher methylation status of in the promoter region of KL (34.1 ± 4.1% vs. 14.6 ± 3.4%, P < 0.01). In PBCCs and vasculature, KL gene expression correlated inversely with pro-inflammatory markers and directly with anti-inflammatory markers. sKL serum levels presented similar associations with the expression levels of pro- and anti-inflammatory markers in PBCCs. The differences in KL expression levels in PBCCs and in serum sKL levels with respect to control group was even greater in those CVD patients with macroscopically observable atheromatous plaques. We conclude that promoter methylation-mediated downregulation of KL gene expression in PBCCs is associated with the pro-inflammatory status in atherosclerotic vascular disease.

Combination of Tocilizumab and Steroids to Improve Mortality in Patients with Severe COVID-19 Infection: A Spanish, Multicenter, Cohort Study.

BACKGROUND: We aimed to determine the impact of tocilizumab use on severe COVID-19 (coronavirus disease 19) pneumonia mortality. METHODS: We performed a multicentre retrospective cohort study in 18 tertiary hospitals in Spain from March to April 2020. Consecutive patients admitted with severe COVID-19 treated with tocilizumab were compared to patients not treated with tocilizumab, adjusting by inverse probability of the treatment weights (IPTW). Tocilizumab's effect in patients receiving steroids during the 48 h following inclusion was analysed. RESULTS: During the study period, 506 patients with severe COVID-19 fulfilled the inclusion criteria. Among them, 268 were treated with tocilizumab and 238 patients were not. Median time to tocilizumab treatment from onset of symptoms was 11 days [interquartile range (IQR) 8-14]. Global mortality was 23.7%. Mortality was lower in patients treated with tocilizumab than in controls: 16.8% versus 31.5%, hazard ratio (HR) 0.514 [95% confidence interval (95% CI) 0.355-0.744], p < 0.001; weighted HR 0.741 (95% CI 0.619-0.887), p = 0.001. Tocilizumab treatment reduced mortality by 14.7% relative to no tocilizumab treatment [relative risk reduction (RRR) 46.7%]. We calculated a number necessary to treat of 7. Among patients treated with steroids, mortality was lower in those treated with tocilizumab than in those treated with steroids alone [10.9% versus 40.2%, HR 0.511 (95% CI 0.352-0.741), p = 0.036; weighted HR 0.6 (95% CI 0.449-0.804), p < 0.001] (interaction p = 0.094). CONCLUSIONS: These results show that survival of patients with severe COVID-19 is higher in those treated with tocilizumab than in those not treated and that tocilizumab's effect adds to that of steroids administered to non-intubated patients with COVID-19 during the first 48 h of presenting with respiratory failure despite oxygen therapy. Randomised controlled studies are needed to confirm these results. TRIAL REGISTRATION: European Union electronic Register of Post-Authorization Studies (EU PAS Register) identifier, EUPAS34415.

Inflammatory Targets in Diabetic Nephropathy.

One of the most frequent complications in patients with diabetes mellitus is diabetic nephropathy (DN). At present, it constitutes the first cause of end stage renal disease, and the main cause of cardiovascular morbidity and mortality in these patients. Therefore, it is clear that new strategies are required to delay the development and the progression of this pathology. This new approach should look beyond the control of traditional risk factors such as hyperglycemia and hypertension. Currently, inflammation has been recognized as one of the underlying processes involved in the development and progression of kidney disease in the diabetic population. Understanding the cascade of signals and mechanisms that trigger this maladaptive immune response, which eventually leads to the development of DN, is crucial. This knowledge will allow the identification of new targets and facilitate the design of innovative therapeutic strategies. In this review, we focus on the pathogenesis of proinflammatory molecules and mechanisms related to the development and progression of DN, and discuss the potential utility of new strategies based on agents that target inflammation.

Cost-effectiveness of the hospital nutrition screening tool CIPA.

INTRODUCTION: Hospital malnutrition is very common and worsens the clinical course of patients while increasing costs. Lacking clinical-economic studies on the implementation of nutrition screening encouraged the evaluation of the CIPA (Control of Food Intake, Protein, Anthropometry) tool. MATERIAL AND METHODS: An open, non-randomized, controlled clinical trial was conducted on patients admitted to internal medicine and general and digestive surgery wards, who were either assigned to a control (standard hospital clinical care) or to an intervention, CIPA-performing ward (412 and 411, respectively; n = 823). Length of stay, mortality, readmission, in-hospital complications, and quality of life were evaluated. Cost-effectiveness was analysed in terms of cost per quality-adjusted life years (QALYs). RESULTS: The mean length of stay was higher in the CIPA group, though not significantly (+ 0.95 days; p = 0.230). On the surgical ward, more patients from the control group moved to critical care units (p = 0.014); the other clinical variables did not vary. Quality of life at discharge was similar (p = 0.53), although slightly higher in the CIPA group at 3 months (p = 0.089). Patients under CIPA screening had a higher mean cost of € 691.6 and a mean QALY gain over a 3-month period of 0.0042. While the cost per QALY for the internal medicine patients was € 642 282, the results for surgical patients suggest that the screening tool is both less costly and more effective. CONCLUSIONS: The CIPA nutrition screening tool is likely to be cost-effective in surgical but not in internal medicine patients.

Association between serum levels of Klotho and inflammatory cytokines in cardiovascular disease: a case-control study.

Decrease in soluble anti-aging Klotho protein levels is associated to cardiovascular disease (CVD). Diverse studies have shown a bidirectional relationship between Klotho and inflammation, a risk factor for the development of CVD. In this work we aimed to evaluate the association between Klotho and inflammatory cytokines levels in the context of human CVD.The study included 110 patients with established CVD and preserved renal function, and a control group of 22 individuals without previous history of cardiovascular events. Serum Klotho and IL10 levels were significantly lower in the CVD group. Inflammatory status, marked by the TNFα/IL10 ratio and the C-reactive protein (CRP) levels, was significantly increased in the group of patients with established CVD. Soluble Klotho levels were directly correlated with eGFR (r=0.217) and IL10 (r=0.209) and inversely correlated with age (r=-0.261), CRP (r=-0.203), and TNFα/IL10 (r=-0.219). This association with TNFα/IL10 remained significant in age-matched subgroups. Multiple logistic regression analysis showed that age, smoking and the neutrophil-to-lymphocyte ratio (NLR) constituted risk factors for the presence of CVD, while Klotho was a protective factor.In conclusion, in patients with established CVD, the reduction in soluble Klotho is associated with a pro-inflammatory status marked by lower IL10 concentrations and higher TNFα/IL10 ratio and CRP levels.

[Pediatric pyomyositis: Experience in a Pediatric Reference Center in Argentina]. / Piomiositis en niños: experiencia en un hospital pediátrico de referencia en Argentina.

BACKGROUND: Pyomyositis is the infection of skeletal muscle, a rare pathology in children. Aim To describe the characteristics of pyomyositis in pediatric patients. METHODS: Prospective analytical study of hospitalized children diagnosed with pyomyositis from May 2016 to April 2017 at the Ricardo Gutiérrez Children's Hospital, Buenos Aires, Argentina. RESULTS: Twenty-one patients with pyomyositis were identified. Annual rate: 21.5/10,000 admissions (95% CI 4.65-71.43). The median age was 5.4 years (range 1.25-11.6). The lower limbs were the most affected site. C-reactive protein (CRP) was elevated in all patients, with a mean of 124 mg/L (SD 96), being significantly higher in patients with bacteremia: 206 (DS 101) vs 98 (DS 81), p = 0.02. Bacterial cultures were positive in 17/21 (80.9%): 15 methicillin-resistant Staphylococcus aureus (MRSA), and 2 Streptococcus pyogenes. Blood cultures were positive in 5 (23.8%). CONCLUSION: MRSA-community acquired is the predominant pathogen in our setting. In the selection of the appropriate empirical treatment, the local resistance pattern and the CRP value should be taken into account.

[Dengue outbreak in Buenos Aires, Argentina, 2016: Clinical and hematological features in children]. / Brote epidémico de dengue en la Ciudad de Buenos Aires, 2016: características clínicas y hematológicas de la infección en una población pediátrica.

Dengue is the human arbovirus with the highest morbidity and mortality in the world. The largest outbreak of dengue in Buenos Aires, Argentina, occurred during 2016. OBJECTIVE: To describe clinical and hematological features in children with confirmed dengue infection. METHODS: Cross sectional study that included children attended since January 18th to April 15th 2016 at Hospital de Niños "Dr. Ricardo Gutiérrez". RESULTS: among 156 registered cases, 82 confirmed cases by virology test; 130 (83 %) autochthonous cases. The most frequent clinical manifestations were fever, headache and retro-ocular pain. Laboratory abnormalities were leukopenia, thrombocytopenia and increased liver enzymes. Thirty-five children were hospitalized (23 %), 25 (16 %) with warning signs. In our study, no cases of severe dengue occurred. CONCLUSIONS: early recognition of warning signs and hematological monitoring is essential in order to detect patients at risk and offer them adequate early treatment.

El dengue es la arbovirosis humana que más morbimortalidad ocasiona mundialmente. Durante 2016, se registró, en la Ciudad de Buenos Aires, Argentina, la mayor epidemia de esta enfermedad. Objetivo: describir las características clínicas y hematológicas en una población pediátrica. Métodos: estudio de corte transversal que incluyó a pacientes atendidos del 18-1-16 al 15-4-16 en el Hospital de Niños "Dr. Ricardo Gutiérrez". Resultados: se registraron 156 casos, 82 confirmados por virología; 130 (83 %), autóctonos. Las manifestaciones clínicas más frecuentes fueron fiebre, cefalea y dolor retroocular. Las alteraciones del laboratorio significativas fueron leucopenia, plaquetopenia y aumento de transaminasas. Se internaron 35 pacientes (23 %), 25 (16 %) con signos de alarma. No se presentó ningún caso de dengue grave. Conclusiones: el reconocimiento oportuno de los signos de alarma y el control hematológico resultan fundamentales para detectar a los niños en riesgo y ofrecerles tratamiento de soporte en forma precoz.

Pentoxifylline for Renal Protection in Diabetic Kidney Disease. A Model of Old Drugs for New Horizons.

Diabetic kidney disease is one of the most relevant complications in diabetes mellitus patients, which constitutes the main cause of end-stage renal disease in the western world. Delaying the progression of this pathology requires new strategies that, in addition to the control of traditional risk factors (glycemia and blood pressure), specifically target the primary pathogenic mechanisms. Nowadays, inflammation is recognized as a critical novel pathogenic factor in the development and progression of renal injury in diabetes mellitus. Pentoxifylline is a nonspecific phosphodiesterase inhibitor with rheologic properties clinically used for more than 30 years in the treatment of peripheral vascular disease. In addition, this compound also exerts anti-inflammatory actions. In the context of diabetic kidney disease, pentoxifylline has shown significant antiproteinuric effects and a delay in the loss of estimated glomerular filtration rate, although at the present time there is no definitive evidence regarding renal outcomes. Moreover, recent studies have reported that this drug can be associated with a positive impact on new factors related to kidney health, such as Klotho. The use of pentoxifylline as renoprotective therapy for patients with diabetic kidney disease represents a new example of drug repositioning.

Fibroblast growth factor 23 expression in human calcified vascular tissues.

Vascular calcification is a major risk for cardiovascular disease and implies the transformation of smooth muscle cells to an osteoblastic phenotype as a consequence of dysregulation of calcium and phosphate metabolism. Fibroblast growth factor (FGF) 23 is the most potent phosphate regulator. Observational studies suggest that high levels of FGF23 are related to cardiovascular morbidity and mortality. In this work, we determined the levels of both the intact and the carboxi-terminal fragments of circulating FGF23 in 133 patients with established cardiovascular disease, the expression of FGF23, its receptors 1 and 3, and its co-receptor Klotho in vascular fragments of aorta, carotid and femoral in 43 out of this group of patients, and in a control group of 20 organ donors. Patients with atherosclerosis and vascular calcification presented increased levels of FGF23 respect to the control group. Vascular immunoreactivity for FGF23 was also significantly increased in patients with vascular calcification as compared to patients without calcification and to controls. Finally, gene expression of FGF23 and RUNX2 were also higher and directly related in vascular samples with calcification. Conversely, expression of Klotho was reduced in patients with cardiovascular disease when comparing to controls. In conclusion, our findings link the calcification of the vascular tissue with the expression of FGF23 in the vessels and with the elevation of circulating levels this hormone.