Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain / Mortalidad y riesgo cardiovascular en vasculitis ANCA. Importancia de la hipertension y funcion renal. Experiencia del sur de España

Background: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). Objectives: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. Methods: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). Results: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. Conclusions: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.(AU)

Introducción: La enfermedad cardiovascular (ECV) es una de las principales causas de muerte en las vasculitis asociadas a anticuerpos anticitoplasma de neutrófilos (ANCA) (VAA). Objetivos: Evaluar la mortalidad y sus causas, entre ellas la ECV y sus factores de riesgo vascular (FRV) en pacientes con VAA en Andalucía. Métodos: Se estudió una cohorte multicéntrica de 220 pacientes con VAA seguidos desde 1979 hasta junio de 2020 en Andalucía. La información, incluidos los datos sociodemográficos y clínicos, se registró retrospectivamente a través de la revisión de historias clínicas. Los datos se analizaron mediante Chi2, ANOVA y regresión de riesgos proporcionales de Cox de forma uni y multivariante con un intervalo de confianza (IC) del 95%. Resultados: Durante un seguimiento medio y desviación estándar de 96,79 ± 75,83 meses, 51 pacientes fallecieron y 30 presentaron al menos un ECV. Los factores pronósticos independientes de mortalidad fueron la edad (HR 1,083, p=0,001) y la creatinina basal (HR 4,41, p=0,01). Los factores pronósticos independientes de ECV fueron la edad [hazard ratio (HR) 1,042, p=0,005] y la presencia de hipertensión arterial (HTA) seis meses después del diagnóstico (HR 4,641, p=0,01). La prevalencia de HTA, diabetes e insuficiencia renal fue elevada o muy elevada en comparación con la población general emparentada, todos FRCV determinantes para el pronóstico de estos pacientes. Conclusiones: La edad y la función renal basal son predictores de mortalidad y la edad y la HTA de aparición precoz son predictores independientes de tener ECV. Se recomienda el cribado de FRCV en pacientes con vasculitis ANCA.(AU)

Mortality and cardiovascular risk in vasculitis ANCA. Importance of hypertension and renal function. Experience from southern Spain.

BACKGROUND: Cardiovascular disease (CVD) is one of the principal causes of death in antineutrophil cytoplasmic antibody-(ANCA)-associated vasculitis (AAV). OBJECTIVES: To evaluate the mortality and it's causes and CVD and its vascular risk factors (VRFs) in AAV patients in Andalusia. METHODS: A multicenter cohort of 220 AAV patients followed-up from 1979 until June 2020 was studied in Andalussia, south of Spain. The information, including socio-demographic and clinical data was recorded retrospectively through chart review. Data was analysed using Chi2, ANOVA and Cox proportional hazards regresion as uni and multivariate test with a 95% confidence interval (CI). RESULTS: During a mean ± standard deviation follow-up of 96.79 ± 75.83 months, 51 patients died and 30 presented at least one CVE. Independent prognostic factors of mortality were age (HR 1.083, p=0.001) and baseline creatinine (HR 4.41, p=0.01). Independent prognostic factors of CVE were age [hazard ratio (HR) 1.042, p=0.005] and the presence of hypertension (HTN) six months after diagnosis (HR 4.641, p=0.01). HTN, diabetes and renal failure, all of these important VRFs, are more prevalent in AAV patients than it is described in matched general population. CONCLUSIONS: Age and baseline renal function, but not CVEs, are predictors of mortality and age and early HTN are independent predictors for having a CVE. CVD screening in AAV patients is demanded.

Impact of plasmapheresis on severe COVID-19.

The clinical course of COVID-19 may show severe presentation, potentially involving dynamic cytokine storms and T cell lymphopenia, which are leading causes of death in patients with SARS-CoV-2 infection. Plasma exchange therapy (PLEX) effectively removes pro-inflammatory factors, modulating and restoring innate and adaptive immune responses. This clinical trial aimed to evaluate the impact of PLEX on the survival of patients with severe SARS-CoV-2 and the effect on the cytokine release syndrome. Hospitalized patients diagnosed with SARS-CoV-2 infection and cytokine storm syndrome were selected to receive 2 sessions of PLEX or standard therapy. Primary outcome was all-cause 60-days mortality; secondary outcome was requirement of mechanical ventilation, SOFA, NEWs-2 scores modification, reduction of pro-inflammatory biomarkers and hospitalization time. Twenty patients received PLEX were compared against 40 patients receiving standard therapy. PLEX reduced 60-days mortality (50% vs 20%; OR 0.25, 95%CI 0.071-0.880; p = 0.029), and this effect was independent from demographic variables and drug therapies used. PLEX significantly decreased SOFA, NEWs-2, pro-inflammatory mediators and increased lymphocyte count, accompanied with a trend to reduce affected lung volume, without effect on SatO2/FiO2 indicator or mechanical ventilation requirement. PLEX therapy provided significant benefits of pro-inflammatory clearance and reduction of 60-days mortality in selected patients with COVID-19, without significant adverse events.

Stability of the Antimicrobial Capacity of Human Milk Against Cronobacter Sakazakii During Handling.

BACKGROUND: Neonatal infections with Cronobacter sakazakii have recently been associated with the consumption of expressed human milk. STUDY AIMS: (1) To evaluate whether human milk has antimicrobial capacity against C. sakazakii and (2) to determine the stability of its capacity when it is subjected to various treatments. METHODS: The antimicrobial capacity of human milk against C. sakazakii was evaluated using an observational, cross-sectional, comparative design. Mature human milk samples (N = 29) were subjected to different treatments. After incubation at 37°C for 72 hr, samples were compared with fresh milk on the stability of their antimicrobial capacity. Two-way analysis of variance (ANOVA) was performed. RESULTS: In fresh milk, counts of C. sakazakii were reduced by 47.26% (SD = 6.74) compared to controls. In treated milk, reductions were: refrigeration at 4°C for 72 hr (M = 33.84, SD = 13.84), freezing at -20°C for 1, 2, and 3 months (M = 40.31, SD = 9.10; M = 35.96, SD = 9.39; M = 26.20, SD = 13.55, respectively), Holder pasteurization (M = 23.56, SD = 15.61), and human milk bank treatment with (M = 14.37, SD = 18.02) and without bovine fortifier (M = 3.70, SD = 23.83). There were significant differences (p < .05) between fresh and treated milk. CONCLUSIONS: Human milk has antimicrobial capacity against C. sakazakii. However, its capacity is negatively influenced by common preservation and hygienization methods. Milk should be stored refrigerated for a maximum of 72 hr or frozen for a short period of time.

Guía de práctica clínica multidisciplinar española sobre la enfermedad de Anderson-Fabry en adultos. I: Método y recomendaciones / Spanish multidisciplinary clinical practice guidelines for Anderson-Fabry Disease in Adults. I. Method and recommendations

La enfermedad de Anderson-Fabry es una afección multisistémica progresiva y grave de origen genético que afecta tanto a hombres como a mujeres y que reduce sus expectativas y calidad de vida. La gran variabilidad en su expresión clínica, las dificultades para su diagnóstico y la disponibilidad actual de varias alternativas para su tratamiento suponen un gran reto que justifica la realización de una guía de práctica clínica basada en la evidencia que pueda ayudar a los profesionales sanitarios en la toma de decisiones en el manejo de estos pacientes. Para elaborarla se ha realizado una búsqueda sistemática en las principales bases de datos bibliográficas mediante estrategias adaptadas a cada una de las 32 preguntas clínicas consideradas. Se confeccionaron fichas para la síntesis y evaluación de la calidad de las evidencias para cada una de las preguntas. La metodología empleada se basa en el Manual metodológico español para la elaboración de guías de práctica clínica e incorpora en la evaluación de la evidencia científica y en la elaboración de las recomendaciones la metodología GRADE, considerando la calidad de la evidencia, el balance entre beneficios y riesgos, valores y preferencias de los pacientes, equidad y uso de recursos. Para la elaboración definitiva de las recomendaciones se llevó a cabo un proceso de consenso estructurado basado en la metodología Delphi-RAND en 2 rondas, con un panel de expertos propuesto por diferentes sociedades científicas, centros de investigación y asociaciones de pacientes. Finalmente, se han elaborado 92 recomendaciones específicas para el manejo de la enfermedad de Fabry

Anderson-Fabry disease is a severe progressive multisystem condition of genetic origin that affects men and women, reducing their life expectancy and quality of life. The considerable variability in its clinical expression, the difficulties in diagnosing the condition and the current availability of several alternatives for its treatment represent a considerable challenge that justifies the development of evidence-based clinical practice guidelines that can help health professionals in the decision-making process for managing these patients. To develop these guidelines, we conducted a systematic search of the main reference databases using strategies adapted to each of the 32 clinical questions considered. We prepared documents to synthesise the evidence and assess its quality for each of the questions. The methodology employed is based on the Spanish methodology manual for preparing clinical practice guidelines, incorporating the GRADE methodology in the assessment of the scientific evidence and the preparation of the recommendations, considering the quality of the evidence, the risk-benefit balance, patient values and preferences, equity and use of resources. For the definitive preparation of the recommendations, we conducted a structured consensus process based on the Delphi-RAND methodology in 2 rounds, with an expert panel proposed by various scientific societies, research centres and patient associations. Ultimately, we developed 92 specific recommendations for managing Fabry disease

Spanish multidisciplinary clinical practice guidelines for Anderson-Fabry Disease in Adults. I. Method and recommendations. / Guía de práctica clínica multidisciplinar española sobre la enfermedad de Anderson-Fabry en adultos. I: Método y recomendaciones.

Anderson-Fabry disease is a severe progressive multisystem condition of genetic origin that affects men and women, reducing their life expectancy and quality of life. The considerable variability in its clinical expression, the difficulties in diagnosing the condition and the current availability of several alternatives for its treatment represent a considerable challenge that justifies the development of evidence-based clinical practice guidelines that can help health professionals in the decision-making process for managing these patients. To develop these guidelines, we conducted a systematic search of the main reference databases using strategies adapted to each of the 32 clinical questions considered. We prepared documents to synthesise the evidence and assess its quality for each of the questions. The methodology employed is based on the Spanish methodology manual for preparing clinical practice guidelines, incorporating the GRADE methodology in the assessment of the scientific evidence and the preparation of the recommendations, considering the quality of the evidence, the risk-benefit balance, patient values and preferences, equity and use of resources. For the definitive preparation of the recommendations, we conducted a structured consensus process based on the Delphi-RAND methodology in 2 rounds, with an expert panel proposed by various scientific societies, research centres and patient associations. Ultimately, we developed 92 specific recommendations for managing Fabry disease.

Determination of lipolytic and proteolytic activities of mycoflora isolated from dry-cured teruel ham.

Fungi play a key role in dry-cured ham production because of their lipolytic and proteolytic activities. In the present study, 74 fungal strains from dry-cured Teruel hams and air chambers were tested for proteolytic and lipolytic activities, with a view to their possible use as starter cultures. Lipolytic activity of fungi was studied against lauric, palmitic, stearic and oleic acids, whereas proteolytic activity was studied against casein and myosin. Of the 74 fungal strains tested, most of them demonstrated lipolytic activity (94.59 %). Lipolytic activity against lauric and oleic acids was stronger than against palmitic and stearic acids. 39 strains (52.70 %) demonstrated proteolytic activity against casein and the 6 highest proteolytic strains were also tested for pork myosin proteolysis. Some strains belonging to Penicillium commune, Penicillium chrysogenum, Penicillium nalgiovense and Cladosporium cladosporioides were selected because of their significant proteolytic and lipolytic activities and could be suitable to use as starters in dry-cured ham.

Mycobiota and toxigenic Penicillium species on two Spanish dry-cured ham manufacturing plants.

The present study reports the natural mycobiota occurring in dry-cured hams, and in particular on the incidence of mycotoxin-producing fungi. A total of 338 fungal colonies were isolated from three stages of production, these being the post-salting, ripening and aging stages in two manufacturing plants. The results show that fungi were more frequently isolated from the aging stage and that the predominant filamentous fungal genus isolated was Penicillium. Seventy-four of the 338 fungal strains were selected for identification at the species level by using morphological criteria and internal transcribed spacers sequencing. Of the 74 fungal strains, 59 were Penicillium strains. Sixteen Penicillium species were identified, with P. commune (24 strains) and P. chrysogenum (13 strains) being the most abundant. The potential ability to produce cyclopiazonic acid (CPA) and ochratoxin A (OTA) was studied by isolating the culture followed by HPLC analysis of these mycotoxins in the culture extracts. The results indicated that 25 (33.7%) of the 74 fungal strains produced CPA. Worth noting is the high percentage of CPA-producing strains of P. commune (66.6%) of which some strains were highly toxigenic. P. polonicum strains were also highly toxigenic. With respect to OTA-producing fungi, a low percentage of fungal strains (9.5%) were able to produce OTA at moderate levels. OTA-producing fungi belonged to different Penicillium species including P. chrysogenum, P. commune, P. polonicum and P. verrucosum. These results indicate that there is a possible risk factor posed by CPA and OTA contamination of dry-cured hams.

Efficacy of low-dose tylvalosin for the control of clostridiosis in broilers and its effect on productive parameters.

The study was carried out under field conditions in a commercial farm, and 1,440 as-hatched Ross-308 broilers were included. Broilers were randomly distributed into 24 experimental 4-m(2) pens (60 broilers/pen). Pens were randomized to the 3 treatment groups: a) tylvalosin 10 mg/kg of live BW during 2 d, b) positive control (tylosin during 2 d), and c) negative control (no treatment). The drugs were provided in the water supply. Mortality, individual BW, and feed intake were assessed. Clostridium presence was assessed in fecal and cecal samples, coccidian oocyst counts were assessed in fecal samples, and bacterial diversity was assessed in ileal content. Live BW at 42 d old was significantly better in the tylvalosin group than in tylosin and no-treatment groups, with tylvalosin-treated broilers reaching 80 to 100 g higher final live weight. Average daily gain results mirrored BW findings. The improvement of feed conversion rate with tylvalosin amounted to 0.13 and to 0.10 versus tylosin and no-treatment, respectively, with mortality being similar in all groups. Significantly reduced sulfite-reducing Clostridium and Clostridium perfringens counts in tylvalosin and tylosin groups versus the no-treatment group were observed in cecum content samples. In conclusion, according to the present study results, tylvalosin, at doses substantially lower than registered for poultry in Europe, has proven effective in controlling the colonization of the cecum by Clostridium ssp. in broilers, improving some productive performances.

Microbiological sampling of carcasses by excision or swabbing with three types of sponge or gauze.

Fifty-five bovine, 50 equine, 60 ovine, and 50 porcine carcasses were sampled in a slaughterhouse in eastern Spain. Two samples were taken from each carcass, one using the excision method and the other using the swabbing method. Four different materials were used for swabbing: cellulose, polyurethane, or viscose sponges, and medical gauze. Samples were collected at the end of the process by four different people before the carcasses were taken to the cooler. The samples were examined for total viable bacteria counts (TVCs) and Enterobacteriaceae counts (ECs). The mean TVC for all species sampled by excision was 4.50 log CFU/cm(2), which was significantly higher than the 3.53 log CFU/cm(2) obtained by swabbing. The TVCs obtained using gauze and the cellulose and polyurethane sponges were significantly higher (P < 0.05) than the corresponding TVCs obtained using viscose sponges. Animal species, the person who collected the samples, and microbiological load also had a significant effect on TVC. ECs were obtained from 82.8% of excision samples, from larger percentages of samples obtained using cellulose or polyurethane sponges or gauze swabs, but from smaller percentages of samples obtained using viscose sponges. The Enterobacteriaceae load significantly influenced the EC. In contrast, animal species and the person who collected the samples had no significant effect. The cellulose sponge, polyurethane sponge, and gauze gave high mean log counts of aerobic bacteria and Enterobacteriaceae, which makes these swab types suitable for use in slaughterhouses for the purpose of assessing production process hygiene.

Treatment of anemia in renal transplantation: impact of a stricter application of hemoglobin targets.

OBJECTIVE: The CREATE and CHOIR studies showed a higher risk for cardiovascular events associated with hemoglobin (Hb) values >13 g/dL in patients with stage 3-4 chronic kidney disease. In 2007, a stricter policy on the use of erythropoietin (EPO) was adopted at our center, with an Hb target of 11 to 12 g/dL and withdrawal or reduction of EPO when Hb was >12.5 to 13 g/dL. This study was designed to evaluate this new approach. MATERIALS AND METHODS: The study included patients under follow-up at the transplant outpatient clinic on December 31, 2006 (n = 725), and December 31, 2007 (n = 768). Data were compared between the study populations concerning renal function, Hb, use of EPO, and associated costs. RESULTS: No significant differences in creatinine or Hb values were observed between the 2 groups (1.47 +/- 0.6 vs 1.42 +/- 0.9 mg/dL and 13.7 +/- 1.5 vs 13.7 +/- 1.6 g/dL, respectively). After implementation of the new protocol, the frequency of severe anemia (Hb <11 g/dL) increased (2% vs 4%; P = .10), the use of EPO decreased (22.1% vs 17.2%; P = .017), and the mean Hb of EPO-treated patients decreased (12.5 +/- 1.4 vs 11.9 +/- 1.0; P < .001). The Hb target (11-12 g/dL) was met in fewer than one third of patients, with no significant differences between the 2 study times. CONCLUSIONS: A strict policy on EPO application reduces its use and the rate of patients with "excessive" Hb values (which are associated with increased cardiovascular risks), with an acceptable slight increase in severe anemia cases.

Factor deficiency in the anemia of renal transplant patients with grade III-IV chronic kidney disease: baseline results of the ARES Study.

ARES is a multicenter, prospective study of the prevalence, management, and repercussions on the quality of life of anemia in renal transplant patients with a reduced renal function (creatinine clearance according to Cockcroft-Gault: 15 mL/min). The frequency of factor deficiency and its relationship with anemia were analyzed at the baseline time of the study. Of the 500 patients included in the main study, valid data were available for iron metabolism in n = 419 microg/dL; folic acid, n = 205 ng/mL; and vitamin B12, n = 210 pg/mL. Anemia was defined as hemoglobin

Prevalence and management of potential candidates for simultaneous pancreas-kidney transplantation in a provincial setting.

INTRODUCTION: Simultaneous pancreas-kidney (SPK) transplantation is the best therapeutic option for correctly selected diabetic patients with advanced chronic kidney disease (CKD). OBJECTIVES: The objectives of this study were to quantify in a Spanish province the prevalence and incidence of type 1 and 2 diabetics with stage IV-V CKD who are potential candidates for SPK, and to analyze the selection for SPK in clinical practice. MATERIALS AND METHODS: All patients with diabetic neuropathy (DN) in predialysis, hemodialysis, or peritoneal dialysis (PD) in our transplantation referral area (population, 1.8 million; data collection ended December 7, 2005) were examined for basic SPK criteria (NTO 2005 Consensus). A new assessment was performed 9 months later, including new possible recipients, and patients were classified as: follows in study, excluded after study, added to SPK waiting list, or SPK-transplanted. RESULTS: In 2005, there were 1371 patients in dialysis or predialysis, including 179 (13%) with DN (41 type 1 and 138 type 2 DM); only 16 of these patients (8.9% of DN patients), 8.9 per million population (PMP), met the basic criteria for SPK transplantation. There were 68 with DN in predialysis, including 8 (11.7%) possible SPK candidates; 7 with DN in PD, no candidates for SPK; and 104 patients with DN in hemodialysis, including 8 (7.2%) SPK candidates. After 9 months, 7 new potential candidates were identified (incidence of 5.1 PMP/y). Of 23 possible candidates, 3 refused SPK, 7 awaited completion of study, 8 were excluded after study, 1 was on the SPK waiting list, and 7 underwent SPK transplantation. CONCLUSIONS: In our setting, approximately 9% of DN patients with stage IV-V CKD were potential SPK candidates in 2005 and 2006. After completion of studies, less than half were eventually included on the waiting list, generating an effective demand for SPK of 2-4 new patients PMP/y.

Influence of the current management of renal transplant recipients on the prevalence of anemia and related costs.

The use of mycophenolate mofetil (MMF) and renin-angiotensin system blockers (RAB) to prevent and treat chronic graft nephropathy may affect the incidence of anemia in renal transplant recipients. We compared 2 sets of cadaver-donor recipients, namely those followed at the end of 1995 (group 1; n = 252) versus 2003 (group 2; n = 530) in terms of general characteristics, incidence of anemia (hemoglobin [Hb] < or =13 g/L males, 12 g/L females) or severe anemia (Hb < or =11 g/L males, 10 g/L females) and use cost of treatment with erythropoietin (EPO). Group 2 was significantly older, heavier and longer since grafting. Fifty-seven percent received MMF, 21% received azathioprine, and 5% received rapamycin. In group 1, 83% were given azathioprine. RAB were administered to 35.1% in group 2 versus 14.7% in group 1 (P < .001). Mean blood pressure was identical in the 2 groups, but graft function was worse in group 2 (Cockroft, 62 vs 74 mL/min; P < .001). Mean Hb levels (13.66 + - 3.1 vs 13.82 + - 1.7 g/L) and prevalence of anemia (36.9% vs 34.5%) for groups 1 and 2, respectively, were similar. The rate of severe anemia, however, was lower in group 2 (2.3% vs 8.7%; P < .001). The use of EPO increased from 2.8% (group 1) to 8.7% (group 2; P < .01). In 2003, the cost of EPO was calculated at 1982 Euros/patient-year and 91,150 Euros per year for the whole patient group. Despite accumulation of predisposing factors, the control of anemia in our patients has improved due to the expanded use of EPO. Along with its high cost, EPO therapy has potential positive repercussions on the quality of life and patient prognosis. Therefore, we need to precisely define the optimal use of EPO in renal transplant recipients.