Síndrome Inflamatorio Multi Sistémico Asociado a COVID 19 en Pediatría / Multi-Systemic Inflammatory Syndrome Associated with COVID 19 in Pediatrics

Si bien la pandemia global por coronavirus pareció afectar en forma leve a los niños, y así fue reportado en Marzo del 2020, por el centro de Control y Prevención (CDC) de China, (epicentro de la pandemia) que describió solo el 1 % del total de la población afectada eran infantes.1 La transmisión a niños ha sido inicialmente descripta a partir de adultos o contactos cercanos portadores de la infección y alguna evidencia de transmisión de la ruta oro-fecal. El periodo de incubación de la enfermedad en niños es entre 2 y 10 días. Si bien la mayoría de ellos son asintomáticos, u oligosintomáticos, los síntomas más comunes reportados en enfermedad aguda han sido fiebre, tos, rinorrea, conjuntivitis y dolor de cabeza. Diarrea, dolor abdominal también pueden presentarse asociados o no a síntomas respiratorios; esto fue descripto en todas las edades de 0 a 19 años. Sólo en el 0.6% ha sido reportada la ocurrencia de una enfermedad severa. A medida que la pandemia progresó en Europa y alineados con formas leves de la enfermedad, otros hallazgos fueron descriptos como la ocurrencia de manifestaciones cutáneas asociadas a SARS- COV2 con peculiar atención a la "perniosis" ya en fases mas tardías de la infección y con buena evolución. Hacia fines de Abril del 2020 desde el Reino Unido, una primera alerta se produjo sobre la ocurrencia de casos más severos en pediatría, referidos desde las unidades de cuidados intensivos, que se caracterizaban por la ocurrencia de miocarditis y síndrome de Shock tóxico. Esto fue reportado inicialmente en 8 niños (1 de ellos falleció), cambiando la mirada para el pediatra sobre la afección por SARS- COV2 en la infancia, con la advertencia de que no siempre se asociada a un desenlace favorable.4 Este reporte también generó alguna confusión ya que algunos de esos niños presentaban un fenotipo de enfermedad similar a la enfermedad de Kawasaki (vasculitis de vaso de mediano calibre que afecta a niños en primera infancia). A partir de esa fecha numerosos reportes han sido publicados con casos similares y diferentes denominaciones: "Shock hiperinflamatorio"; "Síndrome hiperinflamatorio con compromiso multiorgánico" "Síndrome inflamatorio pediátrico Multisistémico (descripto bajo el acrónimo PIMS: Pediatric Inflammatory Multisystem Syndrome") con o sin el sufijo TS que significa asociado temporalmente con infección por SARS-COV2, y "Síndrome símil Kawasaki". Dada la creciente ocurrencia de este síndrome en Europa y las Américas, (ya en Mayo 2020 se describieron mas de 230 niños con este síndrome) motivó a los pediatras, a conocer su patogenia y los diferentes escenarios clínicos bajo el cual estos niños pueden llegar a la consulta. Este es un punto crítico en esta pandemia para el reconocimiento rápido de este grupo de pacientes con enfermedad severa. En nuestro país esta entidad ha sido descripta como SIM-C (Síndrome Inflamatorio Mutisistémico post Covid) por el Ministerio de Salud de la Nación (hacia mediados del mes de Julio 2020). Cabe mencionar que este mismo síndrome también ha sido descripto recientemente en la edad adulta (3 series de casos). En la tabla 1 podemos observar la definición de "caso" (que varia con mínimos cambios ya sea para la OMS, el CDC y nuestro Ministerio). Este síndrome se trata de una entidad inflamatoria, inmunomediada, post infecciosa (post viral) que puede asociarse a estadios de hiperinflamación e hiperferritinemia y se desarrolla en un amplio rango etario de pacientes (0 a 18 años), posterior al contacto estrecho epidemiológico o infección por SARS CoV-2 en 4-6 semanas previas al desarrollo del SIM-C. Esto se manifiesta en la práctica diaria porque la mayoría de los niños tienen serología positiva y estudios de PCR negativo para SARS CoV-2. Esta condición fue descripta por primera vez hacia Mayo 2020 en el Reino Unido como un grupo de niños admitidos a la unidad de cuidados críticos con un cuadro clínico inflamatorio multisistémico con hallazgos similares a la enfermedad de Kawasaki y síndrome de Shock tóxico. Los niños requerían inotrópicos por shock refractario y ventilación mecánica para estabilización cardiovascular más que por falla respiratoria.

Development and Preliminary Validation of the HSQoL-24 Tool to Assess Quality of Life in Patients With Hidradenitis Suppurativa. / Desarrollo y validación preliminar del instrumento HSQoL-24 para evaluar calidad de vida en pacientes con hidradenitis supurativa.

INTRODUCTION AND OBJECTIVES: Hidradenitis suppurativa (HS) is a chronic inflammatory disease of the skin with a negative impact on quality of life. Up to now, there are no disease specific instruments in Spanish to assess quality of life in HS. The objective of this study was to develop and validate a questionnaire to evaluate the quality of life in patients with HS. MATERIAL AND METHODS: A multicentre study was carried out in Spain between 2016 and 2017 to develop the questionnaire. Both the conceptual framework and understanding of the patient's situation were considered through a review of the literature, consensus of professionals from different related health areas, and in-depth interviews with patients. The resulting questionnaire was passed to a group of 30 patients with 30±10 days of interval between both assessments. RESULTS: The reliability analysis shows a good internal consistency and reproducibility with Cronbach's alpha score of 0.920 (test) and 0.917 (retest) and intraclass correlation coefficient with DLQI and Skindex-29 of 0.698 IC 95% (0.456-0.844) and 0.900 IC 95% (0.801-0.951) respectively. Cut-off points were established for its use and the instrument was found to be sensitive to change. CONCLUSIONS: The HSQoL-24 is the first disease-specific self-administered instrument to assess quality of life in patients with HS in Spanish. It is user friendly, and easy to score. This study shows that the instrument is reliable, valid and sensitive to change, pending confirmatory study with a larger sample of 100 patients with HS.

Measurement of the Psychological Impact of Psoriasis on Patients Receiving Systemic Treatment. / Medición del impacto psicológico en pacientes con psoriasis en tratamiento sistémico.

BACKGROUND AND OBJECTIVES: The negative impact of psoriasis on patient quality of life can be as important as the physical consequences of the disease. We could assume that clearance of the disease would also lead to an improvement in its psychosocial impact. The present study assesses the psychological state of patients with psoriasis receiving systemic treatment in a psoriasis unit, especially those with mild or no disease involvement. METHODS: We performed a cross-sectional, observational, noninterventional epidemiological study of 2 cohorts (cases and controls). The patients self-completed demographic data and 4 questionnaires (Rosenberg Self-Esteem Scale, Skindex-29, HADS, and COPE-28 questionnaire) at a single visit. RESULTS: We recruited 111 patients diagnosed with psoriasis and 109 control patients. In self-esteem, the mean and standard deviation (SD) score was 33.5 (4.8) for the psoriasis group and 33.3 (6.7) for the control group, with no significant differences. In the Skindex-29, the mean score for the psoriasis group was almost 3 times higher than that of the control group (30 vs. 11). Significant differences were found in the HADS scores of both groups (12.7 vs. 9.0, P<.001). The mean HADS-A scores were 8.0 (4.78) for the psoriasis group compared with 5.7 (3.8) for the control group (P<.001). In the case of HADS-D, the scores were 4.7 (3.9) compared with 3.2 (3.1) (P<.004), respectively. CONCLUSIONS: Our findings indicate that it is necessary to assess the psychological state of patients with psoriasis, because psychological effects persist even in cases where the disease is almost totally controlled.

A fast-degrading thiol-acrylate based hydrogel for cranial regeneration.

Successful regeneration of the cranium in patients suffering from cranial bone defects is an integral step to restore craniofacial function. However, restoration of craniofacial structure has been challenging due to its complex geometry, limited donor site availability, and poor graft integration. To address these problems, we investigated the use of a thiol-acrylate hydrogel as a cell carrier to facilitate cranial regeneration. Thiol-acrylate hydrogels were formulated with 5-15 wt% poly(ethylene glycol)-diacrylate (PEGDA) and 1-9 mm dithiothreitol (DTT). The degradation rate, swelling ratio, and shear modulus of the resulting hydrogel were first characterized. Then, pre-osteoblast-like cells (MC3T3-E1) were encapsulated in the hydrogel and cultured for up to 21 d. Our results demonstrate that compared to samples formulated from 15 wt% PEGDA, 5 wt% PEGDA samples showed lower storage modulus at day 10 (0.7 kPa versus 8.3 kPa), 62.7% higher in weight change after soaking for 10 d. While the 5 wt% PEGDA group showed an 85% weight loss between day 10 and 21, the 15 wt% PEGDA group showed a 5% weight gain in the same time period. Cell viability with 15 wt% PEGDA and 5 mm DTT hydrogel decreased by 41.3% compared to 5 wt% PEGDA and 5mM DTT gel at day 7. However, histological analysis of cells after 21 d in culture revealed that they had pericellular mineral deposition indicating that the cells were differentiating into osteoblasts lineage in all experimental groups. This study shows that thiol-acrylate hydrogels can be tailored to achieve different degradation rates, in order to enhance cell viability and differentiation. Thus, the findings of this study provide a fundamental understanding for the application of thiol-acrylate hydrogels in cranial bone regeneration.

Minor H antigen matches and mismatches are equally distributed among recipients with or without complications after HLA identical sibling renal transplantation.

Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are scarce and concern mainly single center studies. The International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 16 laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor H antigens and 3 CD31 polymorphisms, was investigated in relation to the incidence of renal graft rejection and graft loss in 444 human leukocyte antigens (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. The correlation between minor H antigen mismatch and the primary outcome graft rejection or graft loss was statistically analyzed. The incidence of rejection was very low and no correlation was observed between one or more minor H antigen mismatch(es) and a rejection episode (n = 36), of which only eight resulted in graft loss. In summary, in our study cohort of 444 renal transplants, mismatching for neither autosomal nor HY minor H antigens correlate with rejection episodes or with graft loss.

Three-way multivariate analysis of metal fractionation results from sediment samples obtained by different sequential extraction procedures and ICP-OES.

Three typical schemes for metal fractionation were applied to analyse coastal surface sediment samples from Bahía Blanca estuary, where an important industrial emplacement is located. Also, three certified reference materials for total metal concentrations were analysed. The studied metals were cadmium, chromium, copper, lead and zinc because of their hazardous potential and related abundance in the estuary. The concentration of metals was determined by inductively coupled plasma-optical emission spectrometry (ICP-OES). A three-way multivariate analysis was performed in order to obtain a better visualization of the experimental data. The extracted information was used to evaluate the equivalence among the results obtained by the three sequential extraction schemes. The data were analysed by parallel factor analysis (PARAFAC). PARAFAC models with two factors describe appropriately the data sets (explained variance about 54% and core consistency of 100%). The multivariate decomposition showed that the three applied schemes are able to describe equally well the behaviour of the metals in the different sediment fractions.

Bone mineral density in hypoparathyroid women on LT4 suppressive therapy. Effect of calcium and 1,25(OH)2 vitamin D3 treatment.

Our aim was to study the bone mineral density (BMD) of patients with chronic hypoparathyroidism (hypoPTH) after longterm calcium and vitamin D treatment. Twenty hypoPTH women (mean-/+SD, aged 50-/+15 years, IPTH 4-/+6 pg/ml) and 20 matched euparathyroid women (euPTH) after near total thyroidectomy for thyroid cancer, completed with I-131 ablation and on suppressive therapy with L-Thyroxine (LT(4)), were studied. In addition eight hypoPTH patients who were receiving LT(4) replacement therapy after surgery for compressive goiter were simultaneously studied. The hypoPTH patients were on calcium and 1,25(OH)(2) vitamin D(3) therapy to normalize serum calcium. Bone mineral density (BMD) (DXA, at the lumbar spine [L(2)- L(4), LS], femoral neck [FN] and Ward triangle [WT]), serum and urine calcium, serum phosphorus, TOTALALP and osteocalcin were measured. Patients with hypoPTH showed greater lumbar BMD than euPTH patients on suppressive therapy (Z-score; 1.01-/+1.34 vs. -0.52-/+0.70, p<0.05). Serum osteocalcin levels were higher in hypoPTH patients on suppressive therapy compared to hypoPTH patients on replacement therapy. The LS BMD from hypoPTH patients correlated with calcium supplements (r=0.439; p=0.02), 1,25(OH)(2)D(3) dose (r=0.382; p=0.04) and LT(4) dose (r=0.374; p=0.05). Our data suggest that long-term treatment with calcium and 1,25(OH)(2) vitamin D3 supplements in hypoPTH patients on suppressive LT4 therapy results in increased BMD when compared with patients with normal PTH levels.

Comparative assessment of two sequential chemical extraction schemes for the fractionation of cadmium, chromium, lead and zinc in surface coastal sediments.

Two existing sequential chemical extraction schemes, involving respectively five and six leaching steps with solutions of increasing dissolving power, were compared. The methods have been applied to surface sediment samples collected in a marine estuary zone potentially exposed to contamination arising from nearby industrial activities. A certified reference material (MURST-ISS-A1) consisting of an Antarctic bottom sediment for which no information regarding phase dependent concentration is available, was also analyzed. In order to evaluate the partition of metals among different geochemical forms, the concentrations of cadmium, chromium, lead and zinc were measured in the liquid extracts by Zeeman-corrected flame atomic absorption and by inductively coupled plasma-atomic emission spectrometry. The total metal concentrations were determined after strong acid attack, and the adequacy of this total digestion/dissolution technique was verified by its application to the reference material. Comparison of total metal concentrations with the sum of concentrations associated with the individual phases was employed to assess possible analyte losses or contaminations. Precisions for both sequential procedures were comparable, but some inconsistencies in mass balances were found in one of the samples for the distribution of Zn in the soluble/exchangeable fractions and for Cd in the bound to carbonates form. In addition, the six steps procedure produced lower concentration values in the case of elements associated to the residual fraction. For the five steps method mass balances showed acceptable agreement, with average recoveries in the 87 to 106% range. On the whole, differences in metal distributions were observed, being more marked for the bottom sediment. Significant proportions of the studied elements, with the exception of Cr, were found as easily extractable forms. X-ray diffraction and petrographic observation of the surface sediments allowed qualitative correlation between the leaching results obtained and the presence of defined geochemical phases.

Bone mineral density and androgen levels in elderly males.

To clarify the relationship of sex male hormones and bone in men, we studied in 140 healthy elderly men (aged 55-90 years) the relation between serum levels of androgens and related sex hormones, bone mineral density (BMD) at different sites, and other parameters related to bone metabolism. Our results show a slight decrease of serum-free testosterone with age, with an increase of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in a third of the elderly subjects studied. BMD decreased significantly with age in all regions studied, except in the lumbar spine. We found a positive correlation between body mass index (BMI) and BMD at the lumbar spine and femoral neck (P < 0.001). No relationship was found (uni- and multivariate regression analysis) between serum androgens or sex hormone-binding globulin (SHBG) and BMD. We found a positive correlation of vitamin D binding protein (DBP) and osteocalcin with lumbar spine BMD and with BMI, DBP, IGF-1, and PTH with femoral neck BMD. In conclusion, there is a slight decline in free testosterone and BMD in the healthy elderly males. However, sex male hormones are not correlated to the decrease in hip BMD. Other age-related factors must be associated with bone loss in elderly males.

[The risk factors and bone mineral density in women on long-term levothyroxine treatment]. / Factores de riesgo y densidad mineral ósea en mujeres en tratamiento prolongado con levotiroxina.

BACKGROUND: It is controversial if the long-term treatment with thyroid hormone given at substitutive or suppressive doses has a negative effect on bone metabolism. In previous reports the lack of ultrasensitive TSH assays and densitometers with adequate precision, and the heterogeneity of the patients analyzed could explain these discordant results. PATIENTS AND METHODS: We have assessed bone mineral density (BMD) in 43 premenopausal and 53 postmenopausal women, who underwent near total thyroidectomy and I-131 ablation due to differentiated thyroid cancer, that have been followed up (mean duration, 75.5 [43] months) with suppressive thyroid hormone treatment (mean dose, 170 [42] micrograms) in our hospital. Patients with history of hyperthyroidism were excluded. Lumbar BMD (L2-L4) and BMD in three different sites of hip were measured (dual X-ray densitometry) to determine the contribution of several clinical and risk factors associated with thyroid hormone therapy given to BMD. RESULTS: We have not found significant decrease in BMD at spine or hip when patients were compared with healthy, age and sex matched. Age (inverse correlation) and weight (direct correlation) were the variables mostly influencing BMD). Histologic type of thyroid neoplasia, doses of thyroid hormones, thyroid hormone levels and duration of follow-up, were not associated with changes in BMD. A decrease in calcium intake in postmenopausal and less physical activity in premenopausal women were related with a decreased lumbar BMD. CONCLUSIONS: During long-term treatment of female patients with thyroid hormones, other risk factors should be studied in order to prevent possible loss of bone mass.

Pyruvate dehydrogenase deficiency: the relation of the E1 alpha mutation to the E1 beta subunit deficiency.

We report 7 patients with pyruvate dehydrogenase (PDH) deficiency caused by mutations of the PDH-E1 alpha subunit. Each patient had a different mutation; 4 with duplicate insertions, 1 with a deletion of tandem repeat, and 2 with point mutations. Five of the mutations were novel, thus confirming allelic heterogeneity. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in every patient. Pulse-labeling and chase study for the E1 alpha and E1 beta subunits revealed that initial synthesis of the mutant E1 alpha subunit was normal and posttranslational degradation was complete by 48 hours. However, the post-translational degradation rate of the E1 beta subunit varied from one patient to another. Factors other than instability of the E1 beta monomer must contribute to the degradation rate of this subunit in the presence of an E1 alpha subunit mutation. Including this series, 3 patients with the S312 deletion and 5 with the R302C point mutation have been reported, and all of these patients are female. These findings suggest that these two loci are hot spots for gene mutations, and may be lethal in the male fetus.

Lack of expression of intercellular adhesion molecule ICAM-1 in lepromatous leprosy patients.

It is conceivable that an abnormal expression of cell-adhesion molecules can contribute to the poor inflammatory response seen in some inflammatory skin diseases. Adhesins are cell-surface molecules that are expressed by many cell types. The main function of adhesins appears to be the promotion of cellular interactions, such as those occurring between immune cells. The epidermis of patients with inflammatory skin diseases exhibits an increased expression of ICAM-1, and it has been postulated that such increased expression can be important in the genesis of cutaneous inflammation. The expression of cell-adhesion molecules (LFA-1, LFA-2, LFA-3 and ICAM-1) in skin lesions of leprosy patients was studied, as well as the in vitro expression of these molecules induced with gamma interferon (IFN-gamma). A lack of expression of ICAM-1 in the epidermis of lepromatous patients was noted; in addition, no expression of ICAM-1 was seen in the nearly normal skin from these patients incubated with IFN-gamma. A similar expression of the four molecules studies was noted in the dermis of both the lepromatous and tuberculoid types of leprosy. The epidermis of the lepromatous leprosy patients appears to have a defective expression of ICAM-1.

[Perspectives on pancreas transplantation in diabetes mellitus type 1]. / Perspectivas del trasplante de páncreas en la diabetes mellitus tipo 1.

Pancreatic transplantation (PT) is a therapeutical procedure which is being currently assessed for the treatment of insulin-dependent Diabetes Mellitus. Organ PT is a real alternative, whereas islets PT is a method still in its clinic and animal experimental stages. Different surgical methods of drainage, preservation, selection of donor, complications and immunosuppressive therapy are analyzed.