Clinical Characteristics and Outcomes of Critically ill Mechanically Ventilated COVID-19 Patients Receiving interleukin-6 Receptor Antagonists and/or Corticosteroid Therapy, the INTERACT study: A Multicenter International Observational Study

ObjectivesThe interest in interleukin-6 receptor antagonists (IL-6RA) and steroids have increased recently due to their potential role as immunomodulatory effect in critically ill coronavirus disease (COVID-19). The magnitude of this therapy in subgroups of patients with invasive mechanical ventilation (MV) remains to be fully clarified. We compared the clinical characteristics and outcomes of patients requiring iMV, and receiving IL-6RA and steroids with different steroids regimens. DesignInternational, multicenter, observational study derived from Viral Infection and Respiratory Illness University Study registry and conducted through Discovery Network, Society of Critical Care Medicine. Marginal structural modeling was used to adjust time-dependent confounders; observations were weighted using inverse probability of treatment weight. A sensitivity analysis was conducted for target trial design. Setting168 hospitals, 16 countries. PatientsCovid-19 ICU patients ([≥]18 years) requiring MV between March 01,2020, and January 10,2021. InterventionNone. Measurements and Main ResultsOf 860 patients met eligibility criteria, 589 received steroids, 170 IL-6RA, and 101 combinations; groups were balanced after adjustment. Median daily steroid dose was 7.5 mg dexamethasone or equivalent (IQR:6-14 mg); 80.8% and 19.2% received low-dose and high-dose steroids, respectively. The median C-reactive protein level was >75 mg/L in majority of our cohort. The use of IL-6R antagonists alone or in combination was not associated with a significant difference in ventilator-free days (VFD) compared to steroids alone with different steroids regimens (adjusted incidence rate ratio [95% CI]): IL-6R antagonists (1.12 [0.88,1.4]), combination (0.83 [0.6,1.14]). Patients treated with low or high-dose steroids had non-significant differences in VFD compared to IL-6RA ({beta}=0.62, 95% CI -1.54,2.78 for low-dose steroid; {beta}=-1.19, 95% CI -3.85,1.47 for high-dose steroid). There was no difference in 28-day mortality and hospital mortality with IL-6RA alone or in combination compared to steroids alone (28-day mortality adjusted odds ratio [95% CI]): IL-6RA (0.68[0.44,1.07]), combination (1.07[0.67,1.70]). Sensitivity analysis findings were consistent with primary analysis. Liver dysfunction was higher in IL-6RA (p=0.04) while rate of bacteremia did not differ among groups. ConclusionsIn adult ICU COVID-19 patients on iMV, we found no difference in outcomes between those who received IL-6RA, steroids, or combination therapy and those who received IL-6RA or low-or high-dose steroids. Further randomized trials are needed to enhance our understanding for IL-6RA safety with different steroids regimen and the magnitude of benefit in those subgroups of patients.

Divertículos caliciales en niños: hallazgos radiológicos y formas de presentación / Calyceal diverticula in children: imaging findings and presentations

El divertículo calicial (DC) es una eventración quística intraparenquimatosa tapizada por epitelio celular transitorio con una estrecha conexión infundibular con los cálices o pelvis del sistema colector renal, por lo que el término más exacto es divertículo pielocalicial. Muy raro en la edad pediátrica, puede ser sintomático y requerir tratamiento. Está infradiagnosticado por confundirse con quistes renales simples por ecografía; su diagnóstico se confirma con tomografía computarizada (TC) o resonancia magnética (RM) en fase excretora, para determinar su seguimiento y manejo. Nuestro objetivo es mostrar las diferentes formas de presentación de los DC en la edad pediátrica, haciendo hincapié en los criterios ecográficos que permiten una aproximación diagnóstica y en los hallazgos definitivos en TC y RM. También discutimos el diagnóstico diferencial con otras lesiones quísticas renales y su tratamiento

A calyceal diverticulum consists of a cystic eventration in the renal parenchyma that is lined with transitional cell epithelium with a narrow infundibular connection with the calyces or pelvis of the renal collector system; thus, the term pyelocalyceal diverticulum would be more accurate. Very rare in pediatric patients, calyceal diverticula can be symptomatic and require treatment. Calyceal diverticula are underdiagnosed because they can be mistaken for simple renal cysts on ultrasonography. To determine the approach to their follow-up and management, the diagnosis must be confirmed by excretory-phase computed tomography (CT) or magnetic resonance imaging (MRI). This article aims to show the different ways that calyceal diverticula can present in pediatric patients; it emphasizes the ultrasonographic findings that enable the lesion to be suspected and the definitive findings that confirm the diagnosis on CT and MRI. It also discusses the differential diagnosis with other cystic kidney lesions and their treatment

Optimization of kidney dysfunction prediction in diabetic kidney disease using targeted metabolomics.

AIMS: Metabolomics have been used to evaluate the role of small molecules in human disease. However, the cost and complexity of the methodology and interpretation of findings have limited the transference of knowledge to clinical practice. Here, we apply a targeted metabolomics approach using samples blotted in filter paper to develop clinical-metabolomics models to detect kidney dysfunction in diabetic kidney disease (DKD). METHODS: We included healthy controls and subjects with type 2 diabetes (T2D) with and without DKD and investigated the association between metabolite concentrations in blood and urine with eGFR and albuminuria. We also evaluated performance of clinical, biochemical and metabolomic models to improve kidney dysfunction prediction in DKD. RESULTS: Using clinical-metabolomics models, we identified associations of decreased eGFR with body mass index (BMI), uric acid and C10:2 levels; albuminuria was associated to years of T2D duration, A1C, uric acid, creatinine, protein intake and serum C0, C10:2 and urinary C12:1 levels. DKD was associated with age, A1C, uric acid, BMI, serum C0, C10:2, C8:1 and urinary C12:1. Inclusion of metabolomics increased the predictive and informative capacity of models composed of clinical variables by decreasing Akaike's information criterion, and was replicated both in training and validation datasets. CONCLUSIONS: Targeted metabolomics using blotted samples in filter paper is a simple, low-cost approach to identify outcomes associated with DKD; the inclusion of metabolomics improves predictive capacity of clinical models to identify kidney dysfunction and DKD-related outcomes.

Calyceal diverticula in children: imaging findings and presentations. / Divertículos caliciales en niños: hallazgos radiológicos y formas de presentación.

A calyceal diverticulum consists of a cystic eventration in the renal parenchyma that is lined with transitional cell epithelium with a narrow infundibular connection with the calyces or pelvis of the renal collector system; thus, the term pyelocalyceal diverticulum would be more accurate. Very rare in pediatric patients, calyceal diverticula can be symptomatic and require treatment. Calyceal diverticula are underdiagnosed because they can be mistaken for simple renal cysts on ultrasonography. To determine the approach to their follow-up and management, the diagnosis must be confirmed by excretory-phase computed tomography (CT) or magnetic resonance imaging (MRI). This article aims to show the different ways that calyceal diverticula can present in pediatric patients; it emphasizes the ultrasonographic findings that enable the lesion to be suspected and the definitive findings that confirm the diagnosis on CT and MRI. It also discusses the differential diagnosis with other cystic kidney lesions and their treatment.

Evolucion de la consanguinidad en el caballo de pura raza española de la yeguada militar respecto al resto de la raza / No disponible

La consanguinidad como método de cría se utiliza desde tiempos remotos, su principal inconveniente es la disminución de la capacidad de adaptación y supervivencia de los individuos con alta tasa de consanguinidad. Se realiza un estudio de la evolución de la consanguinidad de la cabaña equina de Pura Raza Española (PRE) con origen en la Yeguada Militar en comparación con la de la cabaña nacional desde el año 1970. Se detecta una sintonía entre ambas poblaciones (AU)

No disponible

Occurrence of Botryosphaeria obtusa, B. dothidea, and B. parva Associated with Grapevine Trunk Diseases in Castilla y León Region, Spain.

Between 2000 and 2004, 176 vineyards were surveyed for disease symptoms throughout the main grapevine-production areas of Bierzo, Cigales, Ribera del Duero, Rueda, and Toro in the Castilla y León region of Spain. Symptoms resembling Eutypa dieback, such as stunted chlorotic shoots, deformed leaves with necrotic areas, and typical wedge-shaped cankers in the wood, were observed in 80% of surveyed vineyards. The second most common disease observed was esca. The mild form of esca, interveinal chlorosis or reddened patterns on the leaves, was observed in 35% of surveyed vineyards. Severe esca symptoms that include sudden defoliation of some or all parts of the vine followed by shriveling of fruit clusters were observed in vineyards during very hot and dry summer periods. Wood from vines with esca was yellowish, soft, and often partially or completely surrounded by necrotic wood. Black vascular streaking in the wood was also observed in some vines with esca. Samples of wood from vines with symptoms of Eutypa dieback or esca were collected from different cultivars (Tempranillo, Cabernet Sauvignon, Mencía, Garnacha, Viura, and Verdejo). Small pieces of symptomatic wood were placed on 4% potato dextrose agar amended with tetracycline hydrochloride (0.01%) (PDA-tet) and incubated at room temperature. Pure cultures were obtained by excising hyphal tips and transferring to PDA-tet. Species of Botryosphaeria were most frequently isolated from wedge-shaped cankers as well as from wood with necrosis or black vascular streaking. Botryosphaeria spp. also were isolated from the soft yellowish wood, however, Fomitiporia punctata, Stereum hirsutum, and Phaeoacremonium spp. were the most common fungi associated with this symptom. On the basis of morphological characteristics in culture (1), three species were isolated (B. obtusa, B. dothidea, and B. parva). Colonies of B. obtusa were green to dark green with moderate aerial mycelium. Pycnidia developed after 6 days and conidia (n = 50) measured 19 to 27 × 9 to 17 µm and were hyaline and light brown, becoming dark brown when mature, mostly aseptate, and rounded in shape. Colonies of B. dothidea were white, becoming dark green with age and with copious aerial mycelium. Pycnidia started to develop after 10 days, and conidia measured 17 to 31 × 4 to 8 µm, were hyaline, aseptate, and fusiform in shape. Colonies of B. parva were similar in appearance to those of B. dothidea but pycnidia developed after 5 weeks. Conidia measured 11 to 21 × 4 to 9 µm, were hyaline when immature, becoming light brown with two septa with age, and ellipsoidal in shape. Identity of the three Botryosphaeria species was confirmed by comparing morphology with growth of the following identified California isolates: B. obtusa (UCD352Mo and UCD666Na), B. dothidea (UCD1066So), and B. parva (UCD642So) and by comparing sequences of the internal transcribed spacer region (ITSI-5.8S-ITS2) rDNA, and a partial sequence of the ß-tubulin gene (BT2) of our isolates with those of previously identified and sequenced isolates deposited in GenBank. Sequences of B. obtusa (UCD343Spa, UCD461Spa, UCD468Spa, and UCD621Spa), B. dothidea (UCD303Spa), and B. parva (UCD577Spa and UCD578Spa) were deposited in GenBank. To our knowledge, this is the first report of B. obtusa, B. dothidea, and B. parva on grapevines in the Castilla y León region in Spain. Reference: (1) A. J. L. Phillips. Phytopathol. Mediterr. 41:3, 2002.

Hypoalbuminemia as a risk factor for amikacin nephrotoxicity.

Hypoalbuminemia has been recently informed by us as a risk factor in aminoglycoside nephrotoxicity. Since amikacin has a low serum binding capacity to albumin, the present study was designed to determine if the higher risk of amikacin nephrotoxicity in patients with hypoalbuminemia was due to low serum albumin per se or to malnutrition. One-hundred and thirteen ward patients who received endovenous amikacin for greater than 36 hours were studied prospectively. All were evaluated for the following factors: age, sex, diagnosis, serum creatinine, serum albumin, and nutritional status. They were followed with serum creatinine twice a week until cessation of therapy. Amikacin pharmacokinetics was studied in 11 subjects: 6 patients had a serum albumin less than 3.0 g/dL and 5 greater than 3.0 g/dL, but there were no differences in age, sex, weight, diagnosis, arterial pressure and nutritional status. The overall incidence of toxicity was 11%. In patients with serum albumin less than 3.0 g/dL it was 17.3% and in those greater than 3.0 g/dL it was 2.2%, p less than 0.05. There was no difference in the nutritional status between toxicity and non-toxicity groups. In the pharmacokinetic study, the peak levels obtained one hour after amikacin administration were higher in patients with serum albumin less than 3.0 g/dL than in those with normal serum albumin (12.7 +/- 1.6 vs 9.0 +/- 1.2, p less than 0.002). In conclusion hypoalbuminemia is a risk factor in aminoglycoside nephrotoxicity regardless of the nutritional status.

Serial trough and peak amikacin levels in plasma as predictors of nephrotoxicity.

We studied 113 patients treated with intravenous amikacin to determine the value of determining serial trough and peak amikacin levels in plasma for predicting nephrotoxicity. Thirteen patients (11.5%) developed renal toxicity, with significant increases from 48 to 96 h in both peak and trough amikacin levels (6.7 +/- 4.7 [standard deviation] days before the serum creatinine rose). The nontoxicity group had no change or even showed decrements in amikacin levels in plasma. A higher nephrotoxicity risk was seen in patients with increments greater than 1 microgram/ml between 48 and 96 h, with odds ratios of 16.4 for trough, 8 for peak, and 7.2 for both levels. We suggest that an increment of at least 1 microgram/ml in amikacin levels in plasma from 48 to 96 h may predict the appearance of renal toxicity.