Immune Complex Membranoproliferative Glomerulonephritis Associated with Transjugular Intrahepatic Portosystemic Shunts in Alcoholic Cirrhosis: Two Case Reports.

OBJECTIVE: To report on 2 patients with alcoholic cirrhosis who were treated with transjugular intrahepatic portosystemic shunt (TIPS) placement. CLINICAL PRESENTATION AND INTERVENTION: The 2 patients had a history of alcoholic cirrhosis, and TIPS surgery was performed on them. In both cases, 4 months after TIPS placement, proteinuria was observed along with histological alterations characteristic of immune complex membranoproliferative glomerulonephritis (MPGN). CONCLUSION: The TIPS in one patient was successful without immediate complications, while the other patient was referred for a combined liver-kidney transplant. In both cases, immune complex MPGN might have developed after TIPS placement probably due to a reduced immune complex clearance.

Blocking interferon γ reduces expression of chemokines CXCL9, CXCL10 and CXCL11 and decreases macrophage infiltration in ex vivo cultured arteries from patients with giant cell arteritis.

BACKGROUND: Interferon γ (IFNγ) is considered a seminal cytokine in the pathogenesis of giant cell arteritis (GCA), but its functional role has not been investigated. We explored changes in infiltrating cells and biomarkers elicited by blocking IFNγ with a neutralising monoclonal antibody, A6, in temporal arteries from patients with GCA. METHODS: Temporal arteries from 34 patients with GCA (positive histology) and 21 controls were cultured on 3D matrix (Matrigel) and exposed to A6 or recombinant IFNγ. Changes in gene/protein expression were measured by qRT-PCR/western blot or immunoassay. Changes in infiltrating cells were assessed by immunohistochemistry/immunofluorescence. Chemotaxis/adhesion assays were performed with temporal artery-derived vascular smooth muscle cells (VSMCs) and peripheral blood mononuclear cells (PBMCs). RESULTS: Blocking endogenous IFNγ with A6 abrogated STAT-1 phosphorylation in cultured GCA arteries. Furthermore, selective reduction in CXCL9, CXCL10 and CXCL11 chemokine expression was observed along with reduction in infiltrating CD68 macrophages. Adding IFNγ elicited consistent opposite effects. IFNγ induced CXCL9, CXCL10, CXCL11, CCL2 and intracellular adhesion molecule-1 expression by cultured VSMC, resulting in increased PBMC chemotaxis/adhesion. Spontaneous expression of chemokines was higher in VSMC isolated from GCA-involved arteries than in those obtained from controls. Incubation of IFNγ-treated control arteries with PBMC resulted in adhesion/infiltration by CD68 macrophages, which did not occur in untreated arteries. CONCLUSIONS: Our ex vivo system suggests that IFNγ may play an important role in the recruitment of macrophages in GCA by inducing production of specific chemokines and adhesion molecules. Vascular wall components (ie, VSMC) are mediators of these functions and may facilitate progression of inflammatory infiltrates through the vessel wall.

Effects of mefenoxam fungicide on soil biochemical properties.

We studied the effect of mefenoxam on soil biochemical properties. Soil was mixed with three rates of mefenoxam (0.5, 1 and 2 L ha(-1)) and incubated for 83 days. Fungicide was applied to the soil four times during the experiment, according to the manufacturer's instructions. Soil ergosterol, dehydrogenase, urease, ß-glucosidase, and phosphatase activities were measured during the experiment. Compared to controls, soils with the highest doses of mefenoxam demonstrated decreased ergosterol and dehydrogenase activities by 81 and 27 %, respectively; whereas, urease, ß-glucosidase, and phosphatase activities increased. These results suggest that mefenoxam may possibly have consequences for agronomic crop production due to the negative effect on soil fungal populations and stimulation of the growth of soil bacterial activity.

Prospective long term follow-up of a cohort of patients with giant cell arteritis screened for aortic structural damage (aneurysm or dilatation).

BACKGROUND: Aortic structural damage (ASD) may complicate the course of patients with giant cell arteritis (GCA). However the frequency and outcome of ASD has not been assessed in long term prospective studies. METHODS: In a previous screening of 54 biopsy proven GCA patients, significant ASD was detected in 12 (22.2%) after a median follow-up of 5.4 years. These patients were periodically evaluated (every 4 years) over a median of 10.3 years (range 4-16.6 years) in order to investigate the development of new ASD and the outcome of previously detected abnormalities. RESULTS: 18 of the 54 patients abandoned the study due to death or other reasons. The remaining 36 patients were subjected to a second screening and 14 to a third screening. 12 (33.3%) of the 36 patients re-screened and 16 (29.6%) of the initial cohort developed ASD, all but one in the thoracic aorta. Aortic diameters at the ascending and descending aorta significantly increased over time. One patient (1.9% of the initial cohort) died from aortic dissection. Surgery was advised in eight (50%) patients with ASD but could only be performed in three patients (37.7%). The development of ASD was not associated with persistence of detectable disease activity. CONCLUSIONS: The incidence of ASD is maximal within the first 5 years after diagnosis but continues developing over time, affecting up to 33.3% of individuals after long term follow-up. Once ASD occurs, dilatation increases over time, underlining the need for periodic evaluation. Surgical repair is feasible in about one-third of candidates.

Positron emission tomography assessment of large vessel inflammation in patients with newly diagnosed, biopsy-proven giant cell arteritis: a prospective, case-control study.

BACKGROUND: Positron emission tomography (PET) scan is emerging as a promising imaging technique to detect large-vessel inflammation in giant cell arteritis (GCA). However, the lack of a standardised definition of arteritis based on (18)fluorodeoxyglucose (FDG) uptake is an important limitation to the use of PET scan for diagnostic purposes. OBJECTIVE: To prospectively assess the intensity and distribution of FDG uptake at different vascular territories in patients with newly diagnosed GCA compared with controls. METHODS: 32 consecutive, biopsy-proven, GCA patients treated with glucocorticoids for ≤3 days were included. The control group consisted of 20 individuals, who underwent PET/CT for cancer staging. Maximal standardised uptake value (SUVm) was calculated at four aortic segments, supraaortic branches and iliac-femoral territory. Sensitivity and specificity was calculated by receiver-operator characteristic curves (ROC) analysis. RESULTS: Mean SUVm was significantly higher in patients than in controls in all vessels explored and correlated with acute-phase reactants and serum IL-6. Mean of the SUVm at all the vascular territories had an area under the curve (AUC) of 0.830, and a cut-off of 1.89 yielded a sensitivity of 80% and a specificity of 79% for GCA diagnosis. There were no significant differences in AUC among the vascular beds examined. CONCLUSIONS: FDG uptake by large vessels has a substantial sensitivity and specificity for GCA diagnosis.

Changes in biomarkers after therapeutic intervention in temporal arteries cultured in Matrigel: a new model for preclinical studies in giant-cell arteritis.

BACKGROUND: Search for therapeutic targets in giant-cell arteritis (GCA) is hampered by the scarcity of functional systems. We developed a new model consisting of temporal artery culture in tri-dimensional matrix and assessed changes in biomarkers induced by glucocorticoid treatment. METHODS: Temporal artery sections from 28 patients with GCA and 22 controls were cultured in Matrigel for 5 days in the presence or the absence of dexamethasone. Tissue mRNA concentrations of pro-inflammatory mediators and vascular remodelling molecules was assessed by real-time RT-PCR. Soluble molecules were measured in the supernatant fluid by immunoassay. RESULTS: Histopathological features were exquisitely preserved in cultured arteries. mRNA concentrations of pro-inflammatory cytokines (particularly IL-1ß and IFNγ), chemokines (CCL3/MIP-1α, CCL4/MIP-1ß, CCL5/RANTES) and MMP-9 as well as IL-1ß and MMP-9 protein concentrations in the supernatants were significantly higher in cultured arteries from patients compared with control arteries. The culture system itself upregulated expression of cytokines and vascular remodelling factors in control arteries. This minimised differences between patients and controls but underlines the relevance of changes observed. Dexamethasone downregulated pro-inflammatory mediator (IL-1ß, IL-6, TNFα, IFNγ, MMP-9, TIMP-1, CCL3 and CXCL8) mRNAs but did not modify expression of vascular remodelling factors (platelet derived growth factor, MMP-2 and collagens I and III). CONCLUSIONS: Differences in gene expression in temporal arteries from patients and controls are preserved during temporal artery culture in tri-dimensional matrix. Changes in biomarkers elicited by glucocorticoid treatment satisfactorily parallel results obtained in vivo. This may be a suitable model to explore pathogenetic pathways and to perform preclinical studies with new therapeutic agents.

Prevalence and outcomes of fear of falling in older adults with falls at the emergency department: a multicentric observational study.

PURPOSE: Fear of falling (FOF) may result in activity restriction and deconditioning. The aim of the study was to identify factors associated with FOF in older patients and to investigate if FOF influenced long-term outcomes. METHODS: Multicentric, observational, prospective study including patients 65 years or older attending the emergency department (ED) after a fall. Demographical, patient- and fall-related features were recorded at the ED. FOF was assessed using a single question. The primary outcome was all-cause death. Secondary outcomes included new fall-related visit, fall-related hospitalisation, and admission to residential care. Logistic regression and Cox regression models were used for statistical analyses. RESULTS: Overall, 1464 patients were included (47.1% with FOF), followed for a median of 6.2 years (2.2-7.9). Seven variables (age, female sex, living alone, previous falls, sedative medications, urinary incontinence, and intrinsic cause of the fall) were directly associated with FOF whereas use of walking aids and living in residential care were inversely associated. After the index episode, 748 patients (51%) died (median 3.2 years), 677 (46.2%) had a new fall-related ED visit (median 1.7 years), 251 (17.1%) were hospitalised (median 2.8 years), and 197 (19.4%) were admitted to care (median 2.1 years). FOF was associated with death (HR 1.239, 95% CI 1.073-1.431), hospitalisation (HR 1.407, 95% CI 1.097-1.806) and institutionalisation (HR 1.578, 95% CI 1.192-2.088), but significance was lost after adjustment. CONCLUSION: FOF is a prevalent condition in older patients presenting to the ED after a fall. However, it was not associated with long-term outcomes. Future research is needed to understand the influence of FOF in maintenance of functional capacity or quality of life.

Burning Mouth Syndrome Treated with Low-Level Laser and Clonazepam: A Randomized, Single-Blind Clinical Trial.

OBJECTIVE: Burning mouth syndrome (BMS) is a chronic pain disorder characterized by intraoral burning or dysaesthetic sensation, with the absence of any identifiable lesions. Numerous treatments for BMS have been investigated, though without conclusive results. An analysis was conducted of the efficacy of treatment with a low-level diode laser and clonazepam in patients with BMS, and a study was carried out on the levels of different salivary biomarkers before and after treatment. MATERIAL AND METHODS: A randomized, single-blind clinical trial was carried out involving 89 patients divided into the following groups: group 1 (laser, The Helbo® Theralite Laser 3D Pocket Probe + clonazepam) (n = 20), group 2 (sham laser placebo) (n = 19), group 3 (laser) (n = 21) and group 4 (clonazepam) (n = 18). Symptom intensity was scored based on a visual analogue scale (VAS). Sialometry was performed before and after treatment, and the Xerostomia Inventory, Oral Health Impact Profile-14 (OHIP-14) and Mini-Nutritional Assessment (MNA) questionnaires were administered. The following markers were measured in saliva samples: interleukins (IL2, IL4, IL5, IL6, IL7, IL8, IL1ß, IL10, IL12, IL13, IL17, IL21 and IL23), proteins (MIP-3α, MIP-1α and MIP-1ß), GM-CSF, interferon gamma (IFNγ), interferon-inducible T-cell alpha chemoattractant (ITAC), fractalkine and tumor necrosis factor α (TNFα). RESULTS: A significant decrease in the VAS scores was observed after treatment in group 1 (laser + clonazepam) (p = 0.029) and group 3 (laser) (p = 0.005). In turn, group 3 (laser) showed a decrease in the salivary concentration of fractalkine (p = 0.025); interleukins IL12 (p = 0.048), IL17 (p = 0.020), IL21 (p = 0.008), IL7 (p = 0.001) and IL8 (p = 0.007); proteins MIP1α (p = 0.048) and MIP1ß (p = 0.047); and TNFα (p = 0.047) versus baseline. Following treatment, group 1 (laser + clonazepam) showed significant differences in IL21 (p = 0.045) and IL7 (p = 0.009) versus baseline, while group 4 (clonazepam) showed significant differences in IL13 (p = 0.036), IL2 (p = 0.020) and IL4 (p = 0.001). No significant differences were recorded in group 2 (sham laser placebo). CONCLUSIONS: The low-level diode laser is a good treatment option in BMS, resulting in a decrease in patient symptoms and in salivary biomarkers. However, standardization of the intervention protocols and laser intensity parameters is needed in order to draw more firm conclusions.

Increased IL-17A expression in temporal artery lesions is a predictor of sustained response to glucocorticoid treatment in patients with giant-cell arteritis.

BACKGROUND: Interleukin 17A (IL-17A) exerts pivotal proinflammatory functions in chronic inflammatory and autoimmune diseases. OBJECTIVE: To investigate IL-17A expression in temporal artery lesions from patients with giant-cell arteritis (GCA), and its relationship with disease outcome. METHODS: Fifty-seven patients with biopsy-proven GCA were prospectively evaluated, treated and followed for 4.5 years (52-464 weeks). Relapses, time (weeks) required to achieve a maintenance prednisone dose <10 mg/day, and time (weeks) to complete prednisone withdrawal were prospectively recorded. IL-17A mRNA was measured by real-time quantitative RT-PCR in temporal arteries from all patients and 19 controls. IL-17 protein expression was assessed by immunohistochemistry/immunofluorescence. RESULTS: IL-17A expression was significantly increased in temporal artery samples from GCA patients compared with controls (6.22±8.61 vs 2.50±3.9 relative units, p=0.016). Surprisingly, patients with strong IL-17A expression tended to experience less relapses, and required significantly shorter treatment periods (median 25 vs 44 weeks to achieve <10 mg prednisone/day, p=0.0079). There was no correlation between IL-17A and RORc or RORα expression suggesting that these transcription factors may not exclusively reflect Th17 differentiation, and that cells other than Th17 cells might contribute to IL-17 expression in active patients. Accordingly, FoxP3(+)IL-17A(+) cells were identified in lesions by confocal microscopy and were dramatically reduced in specimens from treated patients. CONCLUSIONS: IL-17A expression is increased in GCA lesions, and is a predictor of response to glucocorticoid treatment. The contribution of FoxP3+ cells to IL-17A production in untreated patients suggests that induced-Tregs may facilitate disease remission when proinflammatory cytokine production is downregulated by glucocorticosteroids.

Sex differences in mortality of older adults with falls after emergency department consultation: FALL-ER registry.

BACKGROUND: To investigate if sex is a risk factor for mortality in patients consulting at the emergency department (ED) for an unintentional fall. METHODS: This was a secondary analysis of the FALL-ER registry, a cohort of patients ≥65 years with an unintentional fall presenting to one of 5 Spanish EDs during 52 predefined days (one per week during one year). We collected 18 independent patient baseline and fall-related variables. Patients were followed for 6 months and all-cause mortality recorded. The association between biological sex and mortality was expressed as unadjusted and adjusted hazard ratios (HR) with the 95% confidence interval (95% CI), and subgroup analyses were performed by assessing the interaction of sex with all baseline and fall-related mortality risk variables. RESULTS: Of 1315 enrolled patients (median age 81 years), 411 were men (31%) and 904 women (69%). The 6-month mortality was higher in men (12.4% vs. 5.2%, HR = 2.48, 95% CI = 1.65-3.71), although age was similar between sexes. Men had more comorbidity, previous hospitalizations, loss of consciousness, and an intrinsic cause for falling. Women more frequently lived alone, with self-reported depression, and the fall results in a fracture and immobilization. Nonetheless, after adjustment for age and these eight divergent variables, older men aged 65 and over still showed a significantly higher mortality (HR = 2.19, 95% CI = 1.39-3.45), with the highest risk observed during the first month after ED presentation (HR = 4.18, 95% CI = 1.31-13.3). We found no interaction between sex and any patient-related or fall-related variables with respect to mortality (p > 0.05 in all comparisons). CONCLUSIONS: Male sex is a risk factor for death following ED presentation for a fall in the older population adults aged 65 and over. The causes for this risk should be investigated in future studies.

Influence of income on in-hospital mortality in older adults during the first wave of the COVID-19 pandemic: results from the EDEN-33 study. / Influencia de la renta económica en la mortalidad intrahospitalaria de las personas mayores durante la primera ola de la pandemia por COVID-19: resultados del estudio EDEN-33.

OBJECTIVES: To determine whether income was associated with unexpected in-hospital mortality in older patients treated in Spanish public health system hospital emergency departments. MATERIAL AND METHODS: Fifty-one public health system hospital emergency departments in Spain voluntarily participated in the study. Together the hospitals covered 25% of the population aged 65 years or older included in all patient registers during a week in the pre-pandemic period (April 1-7, 2019) and a week during the COVID-19 pandemic (March 30 to April 5, 2020). We estimated a patient's gross income as the amount published for the postal code of the patient's address. We then calculated the standardized gross income (SGI) by dividing the patient's estimated income by the mean for the corresponding territory (Spanish autonomous community). The existence and strength of an association between the SGI and in-hospital mortality was evaluated by means of restricted cubic spline (RCS) curves adjusted for 10 patient characteristics at baseline. Odds ratios (ORs) for each income level were expressed in relation to a reference SGI of 1 (the mean income for the corresponding autonomous community). We compared the COVID-19 and pre-pandemic periods by means of first-order interactions. RESULTS: Of the 35 280 patients attended in the 2 periods, gross income could be ascertained for 21 180 (60%), 15437 in the pre-pandemic period and 5746 during the COVID-19 period. SGIs were slightly higher for patients included before the pandemic (1.006 vs 0.994; P = .012). In-hospital mortality was 5.6% overall and higher during the pandemic (2.8% pre-pandemic vs 13.1% during COVID-19; P .001). The adjusted RCS curves showed that associations between income and mortality differed between the 2 periods (interaction P = .004). Whereas there were no significant income-influenced differences in mortality before the pandemic, mortality increased during the pandemic in the lowest-income population (SGI 0.5 OR, 1.82; 95% CI, 1.32-3.37) and in higher-income populations (SGI 1.5 OR, 1.32; 95% CI, 1.04-1.68, and SGI 2 OR, 1.92; 95% CI, 1.14-3.23). We found no significant differences between patients with COVID-19 and those with other diagnoses (interaction P = .667). CONCLUSION: The gross income of patients attended in Spanish public health system hospital emergency departments, estimated according to a patient's address and postal code, was associated with in-hospital mortality, which was higher for patients with the lowest and 2 higher income levels. The reasons for these associations might be different for each income level and should be investigated in the future.

OBJETIVO: Determinar si el nivel económico durante la primera ola pandémica tuvo una influencia diferente a la esperable en la mortalidad intrahospitalaria de los pacientes mayores atendidos en los servicios de urgencias (SU) de los hospitales públicos españoles. METODO: Cincuenta y un SU públicos españoles que participaron voluntariamente y que dan cobertura al 25% de la población incluyeron todos los registros de pacientes de edad 65 años atendidos durante una semana del periodo preCOVID (1-4-2019 a 7-4-2019) y una semana del periodo COVID (30-3-2020 a 5-4-2020). Se identificó la renta bruta (RB) asignada al código postal de residencia de cada paciente y se calculó la RB normalizada (RBN) dividiendo aquella por la RB media de su comunidad autónoma. La existencia y fuerza de la relación entre RBN y mortalidad intrahospitalaria se determinó mediante curvas spline cúbicas restringidas (SCR) ajustadas por 10 características basales del paciente. Las OR para cada situación económica se expresó en relación con una RBN de 1 (referencia, renta correspondiente a la media de la comunidad autónoma). La comparación entre periodo COVID y no COVID se realizó mediante el estudio de interacción de primer grado. RESULTADOS: De los 35.280 registros de pacientes atendidos en ambos periodos, se disponía de la RB en 21.180 (60%): 15.437 del periodo preCOVID y 5.746 del periodo COVID. La RBN de los pacientes incluidos fue discretamente superior en el periodo preCOVID (1,006 versus 0,994; p = 0,012). La mortalidad intrahospitalaria fue del 5,6%, y fue superior durante el periodo COVID (2,8% versus 13,1%; p 0,001). Las curvas SCR ajustadas mostraron una asociación entre nivel económico y mortalidad diferente entre ambos periodos (p interacción = 0,004): en el periodo preCOVID no hubo diferencias significativas de mortalidad en función de la RBN, mientras que en el periodo COVID la mortalidad se incrementó en rentas bajas (OR = 1,82, IC 95% = 1,32-3,37 para RBN de 0,5) y en rentas altas (OR = 1,32, IC 95% = 1,04-1,68 y OR = 1,92, IC 95% = 1,14-3,23 para RBN de 1,5 y 2, respectivamente), sin diferencias significativas entre pacientes con COVID y con otros diagnósticos (p interacción = 0,667). CONCLUSIONES: Durante la primera ola de la pandemia COVID, la RB asignada al código postal de residencia de los pacientes atendidos en los SU públicos españoles se asoció con la mortalidad intrahospitalaria, que aumentó en pacientes de rentas bajas y altas. Las razones de estas asociaciones pueden ser distintas para cada segmento económico y deben ser investigadas en el fututo.

Large vessel involvement in biopsy-proven giant cell arteritis: prospective study in 40 newly diagnosed patients using CT angiography.

BACKGROUND: Necroscopic and surgical studies have suggested that giant cell arteritis (GCA) may target the aorta and its main branches. Imaging techniques are able to detect large vessel vasculitis (LVV) non-invasively in patients, but the prevalence of LVV in GCA has not been clearly established. OBJECTIVE: To assess prospectively the prevalence, characteristics and topography of LVV in patients with newly diagnosed GCA and to determine the associated clinical and laboratory features. METHODS: CT angiography (CTA) was performed in 40 consecutive patients with newly diagnosed biopsy-proven GCA. Patients were treatment-naïve or had been treated with corticosteroids for <3 days. Vessel wall thickness and vessel diameter (dilation or stenoses) at four aortic segments (ascending aorta, aortic arch, descending thoracic and abdominal aorta) and at the main aortic branches were evaluated. RESULTS: LVV was detected in 27 patients (67.5%). The vessels involved were as follows: aorta (26 patients, 65%), brachiocephalic trunk (19 patients, 47.5%), carotid arteries (14 patients, 35%), subclavian arteries (17 patients, 42.5%), axillary arteries (7 patients, 17.5%), splanchnic arteries (9 patients, 22.5%), renal arteries (3 patients, 7.5%), iliac arteries (6 patients, 15%) and femoral arteries (11 patients, 30%). Dilation of the thoracic aorta was already present in 6 patients (15%). Cranial ischaemic events were significantly less frequent in patients with LVV (p=0.029). Treatment-naïve patients had a higher frequency of LVV (77% vs 29%, p=0.005). CONCLUSIONS: CTA-defined LVV occurs in two-thirds of patients with GCA at the time of diagnosis and aortic dilation is already present in 15%. Previous corticosteroid treatment may decrease CTA-detected LVV.

Thermography as a Non-Ionizing Quantitative Tool for Diagnosing Burning Mouth Syndrome: Case-Control Study.

OBJECTIVES: Thermography is an imaging technique based on the acquisition and analysis of thermal data. The present study evaluates the use of tongue infrared thermography (IRT) as a tool for the diagnosis of burning mouth syndrome (BMS). MATERIAL AND METHODS: An IRT study was carried out in patients diagnosed with BMS according to the criteria of the International Association for the Study of Pain (n = 32) and in healthy controls (n = 35). Burning sensations, dry mouth and taste disturbances were assessed, and three temperature values were recorded for each tongue surface (dorsal, right lateral, left lateral and tip), along with body temperature and environmental temperature. RESULTS: A statistically significant difference was recorded in the temperature of the dorsal surface of the tongue between the BMS group and the controls (p = 0.01). The area under the curve (AUC) was 0.731 (95% CI: 0.402-0.657; p = 0.003). The sensitivity and specificity obtained was 62% and 77%, respectively. CONCLUSIONS: Infrared thermography appears to be useful as a complementary tool for the diagnosis of BMS, though further studies are needed in this field.

Probability of new falls and factors associated with them in aged patients treated in emergency departments after falling: data from the FALL-ER registry. / Pacientes ancianos atendidos en urgencias por caídas (Registro FALL-ER): probabilidad de nuevas caídas y factores asociados.

OBJECTIVES: To identify characteristics associated with a new fall in a patient who received emergency department care after an accidental fall and to develop a risk model to predict repeated falls. MATERIAL AND METHODS: The FALL-ER registry included accidental falls in patients over the age of 65 years treated in 5 Spanish emergency departments. Independent variables analyzed were patient characteristics at baseline, fall characteristics, immediate consequences, and functional status on discharge. Patients were followed with telephone interviews for 6 months to record the occurrence of new falls. Multivariate regression analysis was used to identify variables associated with falling again and to develop a risk model. We identified 3 levels of risk for new falls (low, intermediate, and high). RESULTS: A total of 1313 patients were studied; 147 patients (11.2%) reported having another fall. Variables associated with risk of falling again were having had a fall in the 12 months before the index fall, neurological disease, anemia, use of non-opioid analgesics, falling at home, falling at night, head injury on falling, and need for help when rising from a chair. The probability of falling again was 3.5%, 10.5%, and 23.3%, respectively, in patients at low, intermediate, and high risk. The model's ability to discriminate was moderate: the area under the receiver operating characteristic curve was 0.688 (95% CI, 0.640-0.736). CONCLUSION: One in 9 older adults treated in an emergency department for an accidental fall will fall again within 6 months. It is possible to identify patients at higher risk for whom preventive measures should be implemented.

OBJETIVO: Investigar las características asociadas a una nueva caída tras la atención en urgencias por una caída no intencionada y desarrollar un modelo de riesgo para predecirla. METODO: El registro FALL-ER incluye pacientes de 65 años o más atendidos por una caída no intencionada en cinco servicios de urgencias españoles. Las variables independientes incluyeron características basales del paciente, de la caída, consecuencias inmediatas y situación funcional al alta. Se realizó seguimiento telefónico para saber si habían existido nuevas caídas en los 6 meses posteriores. Mediante un análisis ajustado se identificaron las variables independientes asociadas a nueva caída y se desarrolló un modelo de riesgo.. RESULTADOS: Se incluyeron 1.313 pacientes y 147 presentaron una nueva caída (11,2%). Las variables asociadas a nueva caída fueron: caída en los 12 meses anteriores, enfermedad neurológica, anemia, toma de analgésicos no opiáceos, caída en domicilio y durante la noche, traumatismo craneoencefálico y necesidad de ayuda para levantarse de la silla. El modelo predictivo mostró una capacidad discriminativa moderada con un área bajo la curva de la característica operativa del receptor de 0,688 (IC 95%: 0,640-0,736). La probabilidad de sufrir una nueva caída fue de 3,5%, 10,5% y 23,3% en los pacientes clasificados como de riesgo bajo, intermedio y alto respectivamente. CONCLUSIONES: Uno de cada nueve adultos mayores que consultan a urgencias por caídas no intencionadas volverán a caer durante los 6 meses siguientes. Es posible identificar un subgrupo de pacientes con riesgo incrementado en los que deberían ponerse en marcha acciones preventivas.

New approaches in the nutritional treatment of advanced chronic kidney disease.

INTRODUCTION: Patients with advanced chronic kidney disease (ACKD) have a high prevalence of malnutrition. The dietary restrictions that we usually apply in terms of macro and micronutrients force our patients to follow dietary guidelines that deviate from healthy patterns. OBJETIVES: To determine if a personalized nutritional intervention program, minimizing the usual restrictions would be justified in case it improved the evolution of kidney disease compared to standard treatment. SECUNDARY OBJETIVES: To determine changes in nutrient intakes and in anthropometric and biochemical parameters, as well as quantify episodes of hyperkalemia. MATERIAL AND METHODS: A single-center, randomized and controlled educational intervention clinical trial was conduct in patients from the ERCA outpatients clinic at the Complejo Hospitalario Universitario de Albacete. 75 patients were included, assigning 35 to a Control group and 40 to the Intervention group with 1-year follow-up. The nutritional status was determined using anthropometric data, body composition by Bioimpedance, blood and urine biochemical parameters and a 24-h recall questionnaire. The nutritional intervention was carried out in three different ways: individual, collective and telephone recall. RESULTS: At the beginning of the study, the BMI showed a situation of weight excess with a mean of 28.83 kg/m2 (5.4) in men and 26.96 kg/m2 (4.09) in women. 70% of our patients had overweight. The abdominal circumference was 105.3 cm (10.2) and 92.3 cm (13.7) for men and women respectively without significant changes throughout the study. The percentage of fat mass (FM) was high in both groups for men and women throughout the study. We did not find biochemical parameters of malnutrition and only significant differences were observed in glomerular filtration rate (GFR), which increased in the intervention group. No patient presented any episodes of hyperkalemia during the study. The energy intake in both groups showed an inadequate distribution of macronutrients with a poor intake of carbohydrates (CH) that was supplemented with an excess of fat. In the case of micronutrients, we did observe an increase in potassium and fiber intakes with a decrease in sodium and phosphorus in the intervention group. CONCLUSIONS: Malnutrition is not exclusively an intake defficit and encompasses both the problems derived from a deficit and an excess of nutrients intake. Un to 70% of our patients showed weight excess and a fat mass higher than desirable. The implementation of an individualized nutritional education program, including a vegetables and fiber rich diet, less atherogenic, not only did not cause electrolyte alterations but also slowed the progression of kidney disease.

Factors associated with late presentation to the emergency department in patients complaining of chest pain.

OBJECTIVE: We investigated which factors predict late presentation (LP) to the emergency department (ED) in patients with non-traumatic chest pain (CP). METHODS: All CP cases attended at a single ED (2008-2017) were included. LP was considered if time from CP onset to ED arrival was>6 h. We analyzed associations between 42 patient/CP-related characteristics and LP in the whole cohort and in patients with CP due to acute coronary syndrome (ACS). RESULTS: The cohort included 25,693 cases (LP=50.6%; ACS=19.0%). Twenty factors were associated with LP, and 8 were also found in patients with ACS: CP of short-duration, aggravated by exertion or breathing/movement, undulating or recurrent CP increased the risk of LP, whereas CP accompanied by diaphoresis, irradiated to the throat, and chronic treatment with nitrates decreased the risk of LP. Exertional and recurrent CP were associated with both, LP and ACS. CONCLUSION: Some characteristics, mainly CP-related, may lead to LP to the ED. CP aggravated by exercise and recurrent CP were associated with both LP and a final diagnosis of ACS. PRACTICE IMPLICATIONS: Patient educational initiatives should consider these two features as potential warnings for ACS and thereby encourage patients to seek early medical consultation.

Tissue and serum markers of inflammation during the follow-up of patients with giant-cell arteritis--a prospective longitudinal study.

OBJECTIVE: To evaluate the association between inflammatory markers and relapse in GCA patients longitudinally assessed in a clinical trial of infliximab and glucocorticosteroids. METHODS: Forty-four newly diagnosed GCA patients in glucocorticosteroid-induced remission were randomized to receive infliximab 5 mg/kg or placebo plus daily glucocorticosteroids, tapered using a standardized schedule. Sera were analysed for inflammatory markers at multiple, pre-defined time points. Temporal artery biopsies were performed in four patients before and after treatment to analyse changes in inflammatory and vascular remodelling marker expression. RESULTS: Thirteen of 44 patients relapsed. Similar proportions of relapsed patients were present in both treatment arms. ESR, CRP, intercellular adhesion molecule (ICAM)-1, TNF-α, and IL-12p40 were significantly elevated near relapse. In post-treatment biopsies, mRNA expression of pro-inflammatory cytokines decreased, while vascular remodelling factors increased relative to baseline biopsies. Tissue IL-12p40 and IFN-γ mRNA remained elevated in relapsing vs remitting patients. CONCLUSION: Despite prior findings of high concentrations of TNF-α in temporal artery biopsies of GCA patients, infliximab plus glucocorticosteroids did not result in improved clinical outcomes. Increased measures of this biomarker did not provide useful insight into the relative importance of TNF-α in the pathogenesis of GCA. Gene expression analysis in paired temporal artery biopsies pre- and post-treatment revealed decreased inflammatory activity and active vascular remodelling following treatment. In relapsing patients, increased expression of IFN-γ and IL-12p40 in post-treatment biopsies suggests a role in sustaining disease and setting the stage for relapse during treatment withdrawal. TRIAL REGISTRATION: ClinicalTrials.gov; http://www.clinicaltrials.gov; NCT00076726.

Effects of Prochloraz fungicide on soil enzymatic activities and bacterial communities.

We studied in the laboratory the effect of Prochloraz fungicide on the biological properties (soil enzymatic activities and soil bacterial communities) of a Plaggic Anthrosol. Five hundred grams of soil (<2mm) was mixed with three dosages of Prochloraz (1, 2, and 4 l ha(-1)) for 83 days. A non-Prochloraz polluted soil was used as control. Following commercial recommendations, fungicide was applied four times during the incubation experiment. For all treatments, the soil ergosterol and levels of dehydrogenase, urease, ß-glucosidase, and phosphatase activity were measured at nine different times (0, 1, 21, 22, 41, 42, 62, 63, and 83 days). The 16S rDNA-DGGE profiles in all treatments were determined at the beginning and end of the incubation period. At the end of the experiment, a significant decrease in ergosterol by 72.3%, 80.8%, and 83.1%, compared with control soil, was observed when 1, 2, and 4 l ha(-1), respectively, was added. Soil enzymatic activities increased when the Prochloraz applied to the soil increased, possibly because the fungicide is used by bacterial communities as a source of energy and nutrients. The 16S rDNA-DGGE profiles indicated that the fungicide did not negatively affect soil bacterial biodiversity. These results suggested that the fungicide Prochloraz has a very interesting agronomic effect, possibly due to the negative effect on soil fungal population stimulating the growth of soil bacterial activity.

Undertriage of patients requiring direct admission to intensive care from the emergency department for medical conditions: impact on prognosis and associated factors. / Infratriaje en urgencias de pacientes que precisan ingreso directo en cuidados intensivos por enfermedades médicas: impacto en el pronóstico y factores asociados.

OBJECTIVES: To determine whether undertriage affects the outcome for patients requiring direct admission to the intensive care unit (ICU) from the emergency department due to a medical condition. To identify factors associated with undertriage. MATERIAL AND METHODS: Retrospective review of patients treated in 2018 for medical emergencies requiring direct admission to the ICU from the emergency department. The cases were classified in 2 groups according to the assigned triage level. Underestimation was defined as a triage level of III or more. Independent variables were demographic and epidemiologic data and indicators of severity recorded in the emergency department. The main outcome was 30-day mortality. Secondary outcomes were in-hospital mortality, prolonged ICU stay, and prolonged hospital stay. RESULTS: We included 470 patients with a median age of 68 years (first-third quartile range, 57-78 years); 61.1% were men, and 151 (32.1%) were undertriaged. Factors directly related to undertriage according to odds ratios (ORs) were age (OR = 1.017; 95% CI, 1.003-1.032), Quick Sequential Organ Failure Assessment score of 0 or 1 (OR = 1.761; 95% CI, 1.038-2.988), ratio of oxygen saturation to fraction of inspired oxygen greater than 300 (OR = 2.447; 95% CI, 1.418-4.223), a diagnosis of infection (OR = 5.003, 95% CI 2.727-9.188) whether respiratory (OR = 3.993, 95% CI 1.919-8.310) or other (OR = 1.980, 95% CI, 1.036-3.785) versus a diagnosis of cardiovascular disease. Factors inversely related to undertriage were admission during the afternoon (OR = 0.512, 95% CI, 0.306-0.856) and ambulance transfer (OR = 0.373; 95% CI, 0.232-0.600). Ninety patients (19.1%) died within 30 days. Undertriage was not related to 30-day mortality or the other outcomes analyzed. CONCLUSION: Undertriage was not associated with a worse outcome in patients requiring direct admission to the ICU for a medical emergency. The factors we found to be associated with undertriage, such as patient age and time of day admitted, merit special attention given that these factors should not be affecting the triage process.

OBJETIVO: Determinar si el infratriaje tiene impacto pronóstico en pacientes que requieren ingreso desde urgencias en cuidados intensivos por enfermedad médica e identificar factores asociados. METODO: Revisión retrospectiva de pacientes atendidos durante 2018 por enfermedades médicas con ingreso directo en cuidados intensivos desde urgencias. Se clasificaron en dos grupos en función del nivel de triaje asignado y se consideró infratriaje un nivel de triaje III. Las variables independientes incluyeron datos demográficos, epidemiológicos e indicadores de gravedad en urgencias. Se registró la mortalidad a los 30 días (objetivo primario), así como la mortalidad hospitalaria, el ingreso prolongado en cuidados intensivos o el ingreso prolongado hospitalario (objetivos secundarios). RESULTADOS: Se incluyeron 470 pacientes [edad 68 años (rango 57-78), 61,1% hombres] de los que 151 (32,1%) formaban el grupo con infratriaje. Los factores relacionados con el infratriaje fueron la edad (OR = 1,017; IC 95% 1,003- 1,032), indicador qSOFA 0-1 (OR = 1,761; IC 95% 1,038-2,988), índice SpO2/FiO2 > 300 (OR = 2,447; IC 95% 1,418- 4,223) y el diagnóstico de infección (OR = 5,003; IC 95% 2,727-9,188), respiratorio (OR = 3,993; IC 95% 1,919-8,310) u otro (OR = 1,980; IC 95% 1,036-3,785) respecto al diagnóstico cardiovascular, mientras que la admisión en horario de tarde (OR = 0,512; IC 95% 0,306-0,856) o el traslado en ambulancia (OR = 0,373; IC 95% 0,232- 0,600) se relacionaron de forma inversa con el infratriaje. El evento mortalidad a 30 días tuvo lugar en 90 pacientes (19,1%). El infratriaje no se relacionó con la mortalidad a 30 días ni con el resto de los objetivos analizados. CONCLUSIONES: El infratriaje no se relacionó con un peor pronóstico en pacientes con ingreso directo en intensivos por enfermedad médica. Se han identificado factores relacionados con el infratriaje, como la edad o el horario de admisión que merecen una atención especial, ya que no deberían afectar el proceso de triaje.

Influence of previous coronary artery bypass grafting in the difficulty of acute coronary syndrome diagnosis.

OBJECTIVES: To investigate whether the diagnosis of acute coronary syndrome (ACS) in coronary artery bypass grafting (CABG) patients with chest pain (CP) is more difficult based on the initial clinical and electrocardiogram (ECG) findings. METHODS: We included consecutive CP patients attended at a single emergency department (ED) during a 10-year period. CABG status and the final diagnosis of ACS were considered as stated in the ED discharge report. We evaluated the frequency of 21 CP characteristics (CPC) and four ECG signatures, their individual and collective association with ACS, and ED length of stay (LOS) in CABG and non-CABG patients. RESULTS: We included 34 429 patients [median age: 61 years; female: 41.8%; CABG: 2204 patients (6.4%)], and ACS was diagnosed in 6727 (19.5%; CABG/non-CABG 37.2%/18.3%; P < 0.001). CABG patients more frequently had CPC and ECG findings typically associated with ACS, but their final association with ACS was weaker than in non-CABG patients (only significant after adjustment for attendant diaphoresis, throat irradiation, ST-segment elevation and T-wave inversion). The collective discriminative capacity was significantly lower in CABG patients (area under the curve 0.710 vs. 0.793; P < 0.001), even after adjustment (0.708 vs. 0.790; P < 0.001). ED LOS was longer for CABG patients, overall (P < 0.001) and for patients diagnosed with ACS (P = 0.008) and non-ACS (P < 0.001), but these differences disappeared after adjustment. CONCLUSION: CABG substantially reduces the diagnostic performance of CPC and ECG findings to suggest ACS. A longer LOS in the ED in CABG patients is more related to their baseline characteristics than to CABG itself.