[Caso clínico: síndrome de DRESS por hidroxicloroquina].

Background: DRESS syndrome (Drug reaction with eosinophilia and systemic symptoms) is an idiosyncratic reaction characterized by peripheral eosinophilia and systemic symptoms: fever, exanthema, lymphadenopathy, hepatitis, atypical lymphocytes and elevated liver enzymes. The incidence is 1 per 10,000 exposures, mortality 10-20%. Treatment is based on suspension of the suspected drug and steroids. Case report: A 42-year-old male with the following important antecedents. AHF: mother and father with Diabetes Mellitus type 2. APP: Arterial Hypertension, Diabetes Mellitus type 2, and bee sting allergy. Current Condition: He started 8 days after ingestion of hydroxychloroquine for probable SARS-COV-2 infection, with headache, facial and neck edema, desquamative dermatosis on trunk and upper extremities, went to private clinic with torpid evolution sent to third level for increased facial and neck edema, which merited orotracheal intubation, management with intravenous steroids and antihistamines. Labs on admission: Leukocytes 20090, platelets 322 thousand, eosinophilia (5%), elevated liver enzymes and acute kidney injury, fulfilling J-SCAR criteria. The patient was discharged due to adequate evolution with follow-up by Allergy and Clinical Immunology, the patient persists with desquamative lesions after 4 weeks and normalization of laboratory parameters. Conclusions: DRESS is a delayed adverse reaction. It is important the diagnostic presumption and the causal relationship with the drugs due to the high mortality rate.

Antecedentes: El síndrome DRESS (Drug reaction with eosinophilia and systemic symptoms) es una reacción idiosincrática, se caracteriza por eosinofilia perifé- rica y síntomas sistémicos: fiebre, exantema, linfadenopatía, hepatitis, linfocitos atípicos y elevación de enzimas hepáticas. La incidencia es de 1 por cada 10,000 exposiciones, mortalidad de 10 a 20%. El tratamiento se basa en la suspensión del fármaco sospechoso y en la aplicación de esteroides. Reporte de caso: Masculino de 42 años con los siguientes antecedentes de importancia. AHF: madre y padre con Diabetes Mellitus tipo 2. APP: Hipertensión Arterial, Diabetes Mellitus tipo 2, y alergia a picadura de abeja. Padecimiento Actual: Lo inicia posterior a 8 días tras la ingesta de hidroxicloroquina por probable infección por SARS-COV-2, con cefalea, edema facial y de cuello, dermatosis descamativa en tronco y extremidades superiores, acude a clínica particular con evolución tórpida enviado a tercer nivel por aumento de edema facial y cuello, que amerito intubación orotraqueal, manejo con esteroides intravenosos y anti- histamínicos. Laboratorios a su ingreso: Leucocitos 20090, plaquetas 322 mil, eosinofilia (5%), elevación de enzimas hepáticas y lesión renal aguda, cumpliendo criterios J-SCAR. Se egresa por adecuada evolución con seguimiento por Alergia e Inmunología Clínica, el paciente persiste con lesiones descamativas posterior a 4 semanas y normalización de parámetros de laboratorios. Conclusión: DRESS es una reacción adversa retardada. Es importante la presunción diagnóstica y la relación causal con los fármacos por la alta tasa de morta- lidad.

Consequences of a low protein diet on the liver and longissimus dorsi transcriptome of Duroc × Iberian crossbred pigs.

Low protein diets supplied during the growing period of pigs can diminish their growth rate and increase the intramuscular fat (IMF) content which affects the sensorial and technological characteristics of the products. In the present study, the effects of a low protein diet supplied during the growing period of Duroc × Iberian crossbred pigs on several phenotypic traits and on liver and longissimus dorsi transcriptome were analysed at the beginning (EARLY) and at the end (LATE) of the growing period. Two experimental groups of 10 crossbred pigs each were fed two isocaloric diets with different protein content: control diet (C) with 16.5% protein and 0.8% lysine and low protein diet (LP) with 11% CP and 0.6% lysine. Animals fed LP diet have a slower growth than those fed C diet, but no effect of LP diet was observed on the IMF content. The transcriptomes of liver and longissimus dorsi were characterised and quantified through RNA-sequencing (RNA-seq). In liver, 134 and 480 differentially expressed annotated genes and new isoforms (DEGs) were detected between C and LP diets for EARLY and LATE animals, respectively. In muscle, 128 and 68 DEGs were detected at EARLY and LATE time-points. Functional interpretation revealed that LP diet may inhibit immune system molecules and processes in both tissues at EARLY stage. In liver, the DEGs mainly affect lipid and cholesterol metabolic processes, while in muscle, the expression changes would be involved in growth, development and meat quality. In conclusion, a low protein diet supplied during the growing period seems to slow down the growth of Duroc × Iberian crossbred pigs, but it also seems to affect multiple biological processes that could compromise the immune system of Duroc × Iberian crossbred pigs. Therefore, these results question the adequacy of this type of regime in Duroc × Iberian pigs that must be studied in greater depth before being implemented.

Changes in the rumen and colon microbiota and effects of live yeast dietary supplementation during the transition from the dry period to lactation of dairy cows.

The first objective of this study was to evaluate the dynamics and their potential association with animal performance of the microbiota in both the rumen and colon of dairy cows as they move from a nonlactation to a lactation ration. The second objective was to assess the potential effects on the microbiota of live yeast supplementation. Twenty-one Holstein cows were split in 2 treatments consisting of 1 × 1010 cfu/d of live yeast (LY; n = 10) or no supplementation (control; n = 11) starting 21 d before until 21 d after calving. At 14 d before and 7 and 21 d after calving, samples of rumen and colon digesta were obtained from each cow using an endoscope. Total DNA was extracted and submitted to high-throughput sequencing. Shannon diversity index, in both the rumen and colon, was unaffected by LY; however, in the rumen it was lowest 7 d after calving and returned to precalving values at 21 d in milk, whereas in the colon it was greatest 14 d before calving but decreased after calving. In the rumen, LY supplementation increased the relative abundance (RA) of Bacteroidales (group UCG-001), Lachnospiracea (groups UCG-002 and UCG-006), and Flexilinea 14 d before calving, and increased RA of Streptococcus 21 d after calving compared with control cows. However, changes in the ruminal microbiota were more drastic across days relative to calving than as influenced by the dietary treatment, and the effect of LY in the colon was milder than in the rumen. The ruminal RA of several genera was associated with postcalving DMI, and that of Gastranaerophilales was the only order positively associated with milk yield. Several genera were positively correlated with feed efficiency, with Clostridiales (unclassified) being the only genus negatively associated with feed efficiency. In the colon, Prevotellaceae (group Ga6A1) was the only genus positively associated with feed efficiency. The ruminal RA of Prevotella 7 and Ruminobacter 14 d precalving was negatively correlated with dry matter intake and milk yield postcalving. The RA of Parabacteroides in the colon 14 d before calving was negatively correlated with milk yield, whereas the RA of Eggerthellaceae (unclassified) and Erysipelotrichaceae (groups c and unclassified) were positively correlated with feed efficiency. Interestingly, LY supplementation doubled the RA of Eggerthellaceae (unclassified) in the colon. It is concluded that microbial diversity in the rumen experiences a transient reduction after calving, whereas in the colon, the reduction is maintained at least until 21 d in milk. Most of the effects of LY on rumen microbiota were observed before calving, whereas in the colon, LY effects were more moderate but consistent and independent of the stage of production. The microbial community of the rumen after calving is more associated with feed intake, milk yield, and feed efficiency than that of the colon. However, the colon microbiota before calving is more associated with feed efficiency after calving than that of the rumen.

Extracolonic Cancer in Inflammatory Bowel Disease: Data from the GETECCU Eneida Registry.

OBJECTIVES: The objective of this study was (a) To know the prevalence and distribution of extracolonic cancer (EC) in patients with inflammatory bowel disease (IBD); (b) To estimate the incidence rate of EC; (c) To evaluate the association between EC and treatment with immunosuppressants and anti-tumor necrosis factor (TNF) agents. METHODS: This was an observational cohort study. INCLUSION CRITERIA: IBD and inclusion in the ENEIDA Project (a prospectively maintained registry) from GETECCU. EXCLUSION CRITERIA: Patients with EC before the diagnosis of IBD, lack of relevant data for this study, and previous treatment with immunosuppressants other than corticosteroids, thiopurines, methotrexate, or anti-TNF agents. The Kaplan-Meier method was used to evaluate the impact of several variables on the risk of EC, and any differences between survival curves were evaluated using the log-rank test. Stepwise multivariate Cox regression analysis was used to investigate factors potentially associated with the development of EC, including drugs for the treatment of IBD, during follow-up. RESULTS: A total of 11,011 patients met the inclusion criteria and were followed for a median of 98 months. Forty-eight percent of patients (5,303) had been exposed to immunosuppressants or anti-TNF drugs, 45.8% had been exposed to thiopurines, 4.7% to methotrexate, and 21.6% to anti-TNF drugs. The prevalence of EC was 3.6%. In the multivariate analysis, age (HR=1.05, 95% CI=1.04-1.06) and having smoked (hazards ratio (HR)=1.47, 95% confidence interval (CI)=1.10-1.80) were the only variables associated with a higher risk of EC. CONCLUSIONS: Neither immunosuppressants nor anti-TNF drugs seem to increase the risk of EC. Older age and smoking were associated with a higher prevalence of EC.

Diagnostic yield of lumbosacral magnetic resonance imaging requested by paediatric urology consultations. / Rentabilidad diagnóstica de la resonancia magnética lumbosacra solicitada desde las consultas de urología pediátrica.

OBJECTIVES: In the historical series, the diagnostic yield of lumbosacral magnetic resonance imaging to rule out occult spinal dysraphism (or occult myelodysplasia), requested by paediatric urology, ranged from 2% to 15%. The aim of this study was to define our cost-effectiveness in children with urinary symptoms and to define endpoints that increase the possibility of finding occult spinal dysraphism. PATIENTS AND METHODS: A screening was conducted on patients with urinary dysfunction for whom an magnetic resonance imaging was requested by the paediatric urology clinic, for persistent symptoms after treatment, voiding dysfunction or other clinical or urodynamic findings. We analysed clinical (UTI, daytime leaks, enuresis, voiding dysfunction, urgency, renal ultrasonography, lumbosacral radiography, history of acute urine retention, skin stigma and myalgia) and urodynamic endpoints (hyperactivity or areflexia, voiding dysfunction, interrupted pattern, accommodation value and maximum flow). A univariate analysis was conducted with SPSS 20.0. RESULTS: We analysed 21 patients during the period 2011-2015. The median age was 6 years (3-10). Three patients (14.3%) had occult spinal dysraphism: one spinal lipoma, one filum lipomatosus and one caudal regression syndrome with channel stenosis. The endpoints with statistically significant differences were the myalgias and the history of acute urine retention (66.7% vs. 5.6%, P=.04; OR= 34; 95%CI: 1.5-781 for both endpoints). CONCLUSIONS: The diagnostic yield of magnetic resonance imaging requested for children with urinary dysfunctions without skin stigma or neuro-orthopaedic abnormalities is low, although nonnegligible. In this group, the patients with a history of acute urine retention and muscle pain (pain, «cramps¼) can experience a greater diagnostic yield or positive predictive value.

Preliminary characterization of dexamethasone-loaded cross-linked hyaluronic acid films for topical ocular therapy.

The aim of this work was to design and characterize cross-linked hyaluronic acid (HA)-itaconic acid (IT) films loaded with dexamethasone sodium phosphate salt (DEX) for topical therapy of inflammatory ocular surface diseases. Films were chemically cross-linked with polyethylene glycol diglycidyl ether (PEGDE), then physical and mechanical characterization by stress-strain, X-ray diffraction, X-ray fluorescence spectrometry and swelling assays was conducted. A sequential in vitro therapeutic efficacy model was designed to assess changes in interleukin (IL)-6 production in an inflamed human corneal epithelial (HCE) cell line after film exposure. Changes in cell proliferation after film exposure were assessed using the alamarBlue(®) proliferation assay. Experimental findings showed desirable mechanical properties and in vitro efficacy to reduce cell inflammation. A moderately decreased proliferation rate was induced in HCE cells by DEX-loaded films, compared to commercial DEX eye drops. These results suggest that DEX and HA have opposite effects. The sequential in vitro therapeutic efficacy model arises as an efficient tool to study drug release from delivery systems by indirect measurement of a biological response.

Novel bioadhesive hyaluronan-itaconic acid crosslinked films for ocular therapy.

New hyaluronic acid (HA)-itaconic acid (IT) films have been previously synthesized and used as potential topical drug delivery systems (DDS) for ocular administration. In this study we explored homogeneous and heterogeneous crosslinking reactions of HA using glutaraldehyde (GTA) and polyethylene glycol diglycidyl ether (PEGDE) in the presence of IT, a naturally occurring compound that is non-toxic and readily biodegradable. We have studied the morphology, mechanical properties and in vitro biocompatibility between these new materials and ocular surface cells (human corneal epithelial cell line) and evaluated the biopharmaceutical performance of the designed formulations. Although all the synthesized materials exhibited good mechanical properties, the PEGDE modified films exhibited the best biocompatibility, with in vivo assays showing good adhesive performance and minimal irritation. PEGDE films were also tested for their effects in the treatment of intraocular pressure (IOP) in rabbits using timolol maleate (TM) as the model drug. These results may be useful for further design of novel bioadhesive matrix containing drugs by topical application in ophthalmology.

A nanomedicine to treat ocular surface inflammation: performance on an experimental dry eye murine model.

MUC5AC is a glycoprotein with gel-forming properties, whose altered expression has been implicated in the pathogenesis of dry eye disease. The aim of our study was to achieve an efficient in vivo transfection of MUC5AC, restore its normal levels in an inflamed ocular surface and determine whether restored MUC5AC levels improve ocular surface inflammation. Cationized gelatin-based nanoparticles (NPs) loaded with a plasmid coding a modified MUC5AC protein (pMUC5AC) were instilled in healthy and experimental dry eye (EDE) mice. MUC5AC expression, clinical signs, corneal fluorescein staining and tear production were evaluated. Ocular specimens were processed for histopathologic evaluation, including goblet cell count and CD4 immunostaining. Neither ocular discomfort nor irritation was observed in vivo after NP treatment. Expression of modified MUC5AC was significantly higher in ocular surface tissue of pMUC5AC-NP-treated animals than that of controls. In healthy mice, pMUC5AC-NPs had no effect on fluorescein staining or tear production. In EDE mice, both parameters significantly improved after pMUC5AC-NP treatment. Anterior eye segment of treated mice showed normal architecture and morphology with lack of remarkable inflammatory changes, and a decrease in CD4+ T-cell infiltration. Thus, pMUC5AC-NPs were well tolerated and able to induce the expression of modified MUC5A in ocular surface tissue, leading to reduction of the inflammation and, consequently improving the associated clinical parameters, such as tear production and fluorescein staining. These results identify a potential application of pMUC5AC-NPs as a new therapeutic modality for the treatment of dry eye disease.

Ectopic origin of coronary arteries from the aorta in Syrian hamsters (Mesocricetus auratus).

An ectopic origin of the coronary artery from the aorta beyond the sinotubular junction, a condition commonly referred to as 'coronary artery high take-off', has been described in man and C57BL/6 mice. The present paper reports this congenital coronary artery anomaly in the Syrian hamster (Mesocricetus auratus). Hearts from 14 individuals, aged 53-350 days, were examined by means of a corrosion-cast technique, scanning electron microscopy or histological and immunohistochemical techniques. In 11 hamsters, the right coronary artery was the ectopic vessel. In the other three animals there was a solitary coronary ostium in the aorta. In all cases, the ectopic coronary artery originated at an acute angle and a valve-like ridge was in front of the coronary artery ostium. The ectopic arteries examined microscopically showed an intramural trajectory within the aortic wall. In the hearts with a solitary ostium in the aorta, the left main coronary artery coursed between the aorta and the pulmonary artery. In man, all of these anomalous conditions place the individual at risk of myocardial ischaemia and sudden death. However, none of the affected hamsters had clinical signs of disease. Intimal thickenings of increasing size with age were present in the intramural coronary artery segment of eight hamsters aged 106 days or older, examined histologically. The present findings fit with the notion that coronary arteries with acute angle take-off and an intramural course are subjected to unusual wear and tear, leading to tissue changes in the vessel wall.

[Our experience in the diagnosis and treatment of cerebral pseudoaneurysms]. / Nuestra experiencia en el diagnóstico y tratamiento de los seudoaneurismas cerebrales.

OBJECTIVE: To present our experience in the diagnosis and intravascular treatment of cerebral pseudoaneurysms. MATERIAL AND METHODS: We present 11 pseudoaneurysms (2 traumatic, 2 mycotic, 3 iatrogenic, and 4 with other causes). We analyze the methods and diagnostic criteria, radiological and clinical outcome, the criteria used in making decisions about treatment, the method of treatment, and the complications. RESULTS: Digital subtraction angiography is the gold standard for the diagnosis of cerebral pseudoaneurysms; the diagnostic criteria in the literature include: aneurysms with early morphological changes and distal aneurysms or proximal aneurysms associated with another distal one, in the context of the right symptoms and signs. In the nine patients treated with endovascular techniques, the treatment objective was achieved and rebleeding did not occur. CONCLUSIONS: In cases with clinical suspicion of a pseudoaneurysm, the patient should undergo angiography. This is especially important in patients with inexplicable cerebral hemorrhage and in those with septicemia. CT angiography and MR angiography have good diagnostic accuracy and can replace conventional angiography. However, the treatment of choice is endovascular and treatment should not be delayed unless access to the pseudoaneurysm is impeded, usually due to severe cerebral vasospasm.

[Carboxypeptidase-G2 administration after high-dose methotrexate. Treatment and drug interactions]. / Administración de carboxipeptidasa tras altas dosis de metotrexato. Tratamiento e interacciones medicamentosas.

Methotrexate (MTX) is widely used as anticancer agent in various malignancies, including acute lymphoblastic leukaemia, lymphoma and osteosarcoma. High doses of MTX may cause acute renal dysfunction. Nephrotoxicity is prevented by the use of alkalinization and hydration. More recently Carboxypeptidase-G2, a recombinant bacterial enzyme that rapidly hydrolyzes MTX to inactive metabolites, has become available for the treatment of acute nephrotoxicity. On the other hand, glutamine is usually administered in oncology treatments to avoid other side effects. We report a case of an adolescent who was diagnosed with T lymphoblastic lymphoma. He was receiving treatment with glutamine when the third course of methotrexate was administered (5 g/m(2)) and he suffered a deterioration in his renal function. Carboxypeptidase was used but the methotrexate serum concentration reduction was not satisfactory. The technique to assess the amount of enzyme-inactivated methotrexate by quantification of MTX metabolites is not available in our country, therefore, the concentrations of MTX may be overestimated. The literature was reviewed to study the influence of glutamine on delayed methotrexate elimination which may lead to acute toxicity.

[Lung transplantation in rats: a viable experimental model]. / Trasplante pulmonar en ratas. Un modelo viable de estudio experimental.

OBJECTIVES: To incorporate a new fast, safe, and reversible anesthetic procedure into the experimental model of lung transplantation (LT) using a cuff technique originally described by Mizuta. MATERIAL AND METHOD: Eighty-eight Sprague-Dawley rats were used in the experimental model. Thirty left LTs were performed, using 60 rats. The donor heart-lung block was excised by median sternotomy with dissection of the left lung and cuffs (intravenous catheters cut into 3-mm sections) were put in place. The left lung was implanted in the recipient by lateral thoracotomy using the cuffs for anastomoses. The duration of surgery and postoperative complications were recorded. Also noted were signs of ischemia-reperfusion injury, and acute rejection of the transplanted lung. RESULTS: We discarded lungs excised from 8 animals when developing the experimental model. Transplants could not be completed in 10 rats due to technical problems, despite satisfactory excision. Of the rats who received a transplant, 4 died in the first 24 hours and 26 survived to 48 hours. They were then killed and examined. The state of the anastomoses was good and signs of ischemia-reperfusion injury, as well as acute rejection were observed in the parenchyma of the transplanted lung. CONCLUSIONS: LT with cuffs in rats is a valid, reliable, reproducible, and cheap model for studying ischemia-reperfusion injury and rejection in LT. The surgical technique is complex, requiring experienced surgeons and a long learning process. Modification of the technique to more closely resemble the surgical procedure in humans is possible, thus facilitating interpretation and allowing more reliable extrapolation to humans.

[Subarachnoid anesthesia for cesarean section in a patient with Ehlers-Danlos syndrome type II]. / Anestesia subaracnoidea para cesárea a una paciente con síndrome de Ehlers-Danlos tipo II.

A 32 year-old woman with full-term pregnancy and a history of Ehlers-Danlos syndrome type II underwent cesarean delivery owing to breech presentation and the presence of oligohydramnios. Anesthesia was provided with a subarachnoid block with 6.5 mg of bupivacaine and 32.5 microg of fentanyl to T4. Depth of anesthesia was adequate and hemodynamic stability was good. The intervention was uneventful and the outcomes were excellent for both mother and fetus. A subarachnoid block with low doses of local anesthetic and fentanyl is an appropriate, safe alternative to general anesthesia for cesarean section in women with Ehlers-Danlos who have normal coagulation tests and no history of bleeding.

[Malnutrition prevalence in institutionalized elderly people in Valencia Community, Spain]. / Prevalencia de malnutrición entre ancianos institucionalizados en la Comunidad Valenciana.

BACKGROUND: The goal of this study was to know the prevalence of malnutrition in an institutionalized elderly population according to age and sex. PATIENTS AND METHOD: We studied 615 institutionalized patients, with a mean age (SD) of 79.33 (9.07) years. Anthropometric parameters included weight, height, knee-heel length, tricipital and subescapular skin folds, arm perimeter and fat mass. Biochemical parameters included: total cholesterol, triglycerides, albumin, prealbumin, transferrin,retinol-binding protein, C3 and lymphocyte count. Malnutrition prevalence was 26.87% (CI 95%, 23.15-30.86), 29.08% (CI 95%, 22.82-35.97) in men and 25.59% (CI 95%, 25.01-30.61) in women. Anthropometric parameters were found to be decreased in all malnourished patients. Significant decreases in albumin and retinol-binding protein concentrations were observed in some age groups of malnourished patients. We also found a decrease in the total cholesterol level in parallel to an age increase in both sexes, regardless of the nutritional status. Triglyceride levels were significantly decreased in both males and females with malnutrition. CONCLUSIONS: We detected a high prevalence of malnutrition, yet lower than reported in other studies with similar age groups.

[Efficacy and safety of fexofenadine and cetirizine in the treatment of allergic rhinitis]. / Eficacia y seguridad de la fexofenadina y la cetirizina en el tratamiento de la rinitis alérgica.

BACKGROUND: Allergic rhinitis affects 20 million of people in United States and a higher figure all around the world. OBJECTIVE: To evaluate the efficacy and safety of fexofenadine compared with certirizine in the treatment of allergic rhinitis. MATERIAL AND METHOD: It was carried out a prospective, double blind, comparative, randomized and multicentric study in patients with allergic rhinitis, with ages between 12 and 65 years. In the first phase, placebo was administered during three days to all the patients; and then, they were randomly allocated to receive fexofenadine 120 mg or cetirizine 10 mg in one dose a day during 14 days. Laboratory and cabinet tests at the beginning and at the end were performed to value security, as well as a global evaluation of the researcher to estimate effectiveness. RESULTS: 176 patients were included, 63.6% were women, average age was 27 years (+/- 12), 47.7% received fexofenadine and 52.2%, cetirizine. There was not significant difference in parameters of effectiveness nor of security in the studied group. CONCLUSION: The results of the present study confirm the efficacy and safety of the antihistaminic fexofenadine in the treatment of allergic rhinitis.