Severe eosinophilic fasciitis: comparison of treatment with D-penicillamine plus corticosteroids vs. corticosteroids alone.

OBJECTIVES: To compare the therapeutic effectiveness of corticosteroids (CS) alone vs. CS plus d-penicillamine (d-Pen) in severe eosinophilic fasciitis. METHOD: A long-term prospective non-randomized trial of d-Pen plus CS vs. CS alone in patients with severe eosinophilic fasciitis, defined as clinically apparent cutaneous fibrotic involvement affecting more than 15% body surface area (BSA) or more than 10% BSA with joint flexion contractures. RESULTS: Sixteen patients with severe eosinophilic fasciitis entered the study. Ten patients received d-Pen plus CS and six received CS alone. Affected BSA decreased from an average of 29% to 8.9% in the d-Pen plus CS group compared to a decrease in affected BSA from 28% to 22.83% in the CS-alone group. The reduction in affected BSA in the d-Pen plus CS group was significantly greater than in the CS-alone group (p = 0.038). Clinical improvement occurred in all d-Pen plus CS patients compared to only 33.3% of CS-alone patients (p = 0.008). There was no difference in overall frequency of adverse events between the groups (p = 0.60). The most common adverse event in the d-Pen plus CS group was proteinuria (33.3%). However, proteinuria also occurred in 16.6% in the CS-alone group. CONCLUSIONS: Treatment with CS alone failed to induce clinical improvement in the majority of the severe eosinophilic fasciitis patients. By contrast, d-Pen plus CS resulted in significantly greater clinical improvement. These results suggest that initial treatment of severe eosinophilic fasciitis with CS alone is not sufficient for optimal therapeutic response and that addition of an antifibrotic agent results in an improved outcome.

[Graves’ orbitopathy in pediatrics]. / Orbitopatía de Graves en pediatría.

Graves’ orbitopathy (GO) is rare in pediatric patients, however is the most common extrathyroid manifestation of Graves’ disease (GD), being present in 30-67% of patients. GO is an autoimmune inflammatory disorder involving orbital connective and fatty tissues as well as the extraocular muscles. In children, GO is less common and less severe than in adults. The most common symptoms are upper eyelid retraction, conjunctival injection, and proptosis and periorbital edema. Severe complications include dysthyroid optic neuropathy, corneal ulceration and eyeball subluxation. The diagnosis is established by clinical, laboratory and imaging findings. There are no management guidelines for GO in children but adult recommendations include the assessment of clinical activity and its severity, to implement the best treatment. Supportive therapies are intended to relieve symptoms and prevent corneal damage in mild cases. Tobacco exposure should also be avoided. The first line of treatment is systemic administration of corticosteroids in active and severe cases. Other options as somatostatin use and retrobulbar radiation have not been used in children, therefore their use is not recommended.

Verrucous hemangioma with pseudoepitheliomatous epidermal hyperplasia in an adult horse.

Verrucous hemangiomas are a rare specific variant of equine skin tumors not well described in the literature. An 8-year-old gelding presented a unilateral lesion on the pastern. Macroscopically, the mass showed a warty and verrucous surface with focal ulcerations. The histology showed a dermal proliferation of endothelial-layered capillaries and venules separated by a delicate stroma of scant fibroblasts and collagen deposition, with pseudoepitheliomatous hyperplasia (exuberant reactive irregular epithelial hyperplasia with tongue-like projections extending into the dermis, mimicking downgrowth of squamous cell carcinoma) and orthokeratotic hyperkeratosis of the overlying epidermis. The immunohistochemical study confirmed the endothelial origin of the tumor, and a final diagnosis of verrucous hemangioma with pseudoepitheliomatous hyperplasia was confirmed. To the knowledge of the authors, this is the first detailed description of this entity in adult horses. Moreover, the clinical progression and epidermal changes have not been previously reported, emphasizing the importance of a pathological study of any epithelial preneoplastic lesion to rule out an underlying dermal neoplasia.

[Clinical relevance of the K-ras oncogene in colorectal cancer: experience in a Mexican population]. / Relevancia clínica del oncogén K-ras en cáncer de colon, experiencia en una población mexicana.

BACKGROUND: Colorectal cancer is frequent in the developed countries, with a cancer-specific mortality rate of 33%. Different biomarkers are associated with overall survival and the prediction of monoclonal treatment effectiveness. The presence of mutations in the K-ras oncogene alters the response to target therapy with cetuximab and could be an independent prognostic factor. AIMS: To analyze the difference in survival between patients with mutated K-ras and those with K-ras wild-type status. METHODS: Thirty-one clinical records were retrospectively analyzed of patients presenting with colorectal cancer that underwent K-ras sequencing through real-time polymerase chain reaction within the time frame of 2009 to 2012 at the Hospital de Alta Especialidad de Veracruz of the Instituto para la Salud y Seguridad Social de los Trabajadores del Estado (HAEV-ISSSTE). Survival analysis for patients with and without K-ras mutation was performed using the Kaplan Meier method. Contrast of covariates was performed using logarithmic transformations. RESULTS: No statistically significant difference was found in relation to survival in the patients with mutated K-ras vs. those with K-ras wild-type (P=.416), nor were significant differences found when analyzing the covariants and survival in the patients with mutated K-ras: ECOG scale (P=.221); age (less than, equal to or greater than 65years, P=.441); clinical stage according to the AJCC (P=.057), and primary lesion site (P=.614). CONCLUSIONS: No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature. Further studies that include both a larger number of patients and those receiving monoclonal treatment, need to be conducted. There were only 5 patients in the present study that received cetuximab, resulting in a misleading analysis.

Efficiency of biological and mechanical-biological treatment plants for MSW: The case of Spain.

Biological and mechanical biological treatment plants combine mechanical and biological treatments to recover the greatest possible amount of materials from municipal solid waste (MSW) and biostabilize the organic fraction to be landfilled or applied in land. These plants handle a high percentage of the MSW generated in Europe. This work presents an exhaustive analysis of the existing plants in Spain which evaluates their typology as well as their performance. In Spain, 137 plants, which receive 13 Mt/year of waste, provide the country with total coverage. Twenty-two types of plants have been identified and grouped into six categories. There are four categories that receive mixed MSW: 1) sorting plants; 2) recovery and composting plants; 3) biodrying and recovery plants; and 4) recovery, biomethanation and composting plants and two that receive separately collected biowaste: 5) composting plants, and 6) biomethanation and composting plants. In plants that receive mixed waste, around 5% of the total input is recovered as recyclable materials (662,182 t/year), of which 29% corresponds to plastics, 27% to metals, and 27% to paper and cardboard. In addition, biostabilized material and/or biogas, and rejects (45-77% of the input) are obtained. In the biowaste plants, high-quality compost (more than 105,000 t/year), a higher biogas yield (43.60 Nm3/t·year) and a lower proportion of rejects (around 29%) are obtained.

Effect of airflow on biodrying of gardening wastes in reactors.

Biodrying consists of reducing moisture by using the heat from aerobic bio-degradation. The parameters that control the process are: aeration, temperature during the process, initial moisture of biowaste, and temperature and relative humidity of the input air. Lawn mowing and garden waste from the gardens of the University Jaume I, Castellón (Spain) were used as a substrate. Biodrying was performed in 10 reactors with known air volumes from 0.88 to 6.42 L/(min x kg dry weight). To promote aeration, 5 of the reactors had 15% of a bulking agent added. The experiment lasted 20 days. After the experiments it was found that the bulking agent led to greater weight loss. However, the increased airflow rate was not linearly proportional to the weight loss.

Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation.

BACKGROUND: Explore safety and efficacy of three palonosetron-containing regimens for emesis prevention over 7 days in multiple myeloma (MM) patients receiving melphalan (100 mg/m(2)) and hematopoietic stem cell transplantation (HSCT). PATIENTS AND METHODS: Randomized, double-blind pilot study in MM patients (n=73) receiving 1, 2, or 3 days of 0.25 mg palonosetron (30-s i.v. bolus) 30 min before melphalan (days -2 and -1) and HSCT (day 0). Patients received dexamethasone (20 mg i.v., days -2 and -1) immediately before or after study drug/placebo. Daily diaries recorded emesis, rescue medication, nausea duration, and adverse events (AEs). RESULTS: Seven-day complete protection (no emesis) occurred in 41.7% [95% confidence interval (CI) 22.1% to 63.4%], 41.7% (95% CI 22.1% to 63.4%), and 44.0% (95% CI 24.2% to 65.1%) of patients receiving 1, 2, or 3 days of palonosetron, respectively (P=0.43). Complete response (emesis free without rescue medication) occurred in 8.3%, 20.8%, and 20.0% (P=0.14). Common AEs (≥10%) were mild-to-moderate diarrhea, constipation, headache, insomnia, and flatulence. No serious AEs occurred. CONCLUSIONS: Palonosetron with dexamethasone was safe and effective in preventing emesis in MM patients receiving melphalan and HSCT. This pilot study with a limited number of patients suggests that multiple doses of palonosetron could be more effective than a single dose in making patients emesis free without need for rescue medication. However, even multiple doses of palonosetron resulted in only 20% of patients being emesis free without rescue medication, suggesting that further improvement will require development of more effective combination antiemetic therapy.

Population structure of mycobionts and photobionts of the widespread lichen Cetraria aculeata.

Lichens are symbioses between fungi (mycobionts) and photoautotrophic green algae or cyanobacteria (photobionts). Many lichens occupy large distributional ranges covering several climatic zones. So far, little is known about the large-scale phylogeography of lichen photobionts and their role in shaping the distributional ranges of lichens. We studied south polar, temperate and north polar populations of the widely distributed fruticose lichen Cetraria aculeata. Based on the DNA sequences from three loci for each symbiont, we compared the genetic structure of mycobionts and photobionts. Phylogenetic reconstructions and Bayesian clustering methods divided the mycobiont and photobiont data sets into three groups. An amova shows that the genetic variance of the photobiont is best explained by differentiation between temperate and polar regions and that of the mycobiont by an interaction of climatic and geographical factors. By partialling out the relative contribution of climate, geography and codispersal, we found that the most relevant factors shaping the genetic structure of the photobiont are climate and a history of codispersal. Mycobionts in the temperate region are consistently associated with a specific photobiont lineage. We therefore conclude that a photobiont switch in the past enabled C. aculeata to colonize temperate as well as polar habitats. Rare photobiont switches may increase the geographical range and ecological niche of lichen mycobionts by associating them with locally adapted photobionts in climatically different regions and, together with isolation by distance, may lead to genetic isolation between populations and thus drive the evolution of lichens.

[Mesenteric solitary fibrous tumor: a case report and literature review]. / Tumor fibroso solitario en mesenterio: reporte de un caso y revisión de la literatura.

Solitary fibrous tumors are a very unusual group of spindle-cell neoplasm of adults; they were described for first time in the 18th century. They locate mainly in parietal and visceral pleura, lung parenchyma and pericardium. There are numerous reports that document their extrapleural location and we can find it in any place in the body, but mesenteric localization is extremely unusual.

[Gastric duplication in adults: a case report and literature review]. / Duplicación gástrica en adultos; informe de un caso y revisión de la bibliografía.

Duplications of the gastrointestinal tract are a rare congenital malformations that usually presents in the first 2 years of life with symptoms of poor weight gain and abdominal palpable mass. The present is a case report of 41 year-old woman who was evaluated for upper abdominal pain. Upper endoscopy revealed a submucosal mass in the greater curvature of the stomach with initial suspect diagnosis of gastrointestinal stromal tumor. Endoscopic ultrasound confirmed partially cystic submucosal mass which was removed with a distal gastric wedge resection without complications. Histopathological report was congenital gastric duplication.

Energy hormone response to fasting-induced dyslipidemia in obese and non-obese donkeys.

Metabolic and endocrine disorders, such as dyslipidemia, are common in donkeys. Negative energy balance due to fasting, stressful conditions, or disease is a major trigger for fat mobilization often leading to dyslipidemia. The hormonal response to fasting has not been well characterized in donkeys. Therefore, this work aimed to study variations in insulin, glucagon, leptin, total adiponectin, ghrelin, and insulin-like growth factor-1 concentrations, insulin-to-glucagon (IGR) and glucagon-to-insulin (GIR) molar ratios, and lipid and carbohydrate parameters during a 66 h fasting period in 8 adult donkeys, and to determine differences depending on body condition. Obese donkeys developed earlier lipid mobilization (increased plasma total triglyceride and total cholesterol concentrations) compared to non-obese donkeys. Plasma glucose and leptin concentrations decreased in obese animals. After 60 h fasting, obese donkeys showed a significant increase in glucagon and decrease in leptin. GIR significantly increased, while insulin and IGR decreased in both groups. These findings support faster lipid mobilization in response to negative energy status in obese donkeys during fasting, which could be linked to greater glucagonemia and could explain the predisposition of these animals to dyslipidemia.

Role of Tonsillar Chronic Inflammation and Commensal Bacteria in the Pathogenesis of Pediatric OSA.

Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We have previously demonstrated that these tonsils present a defective regulatory B cell (Breg) compartment. Here, we extend those findings by uncovering the crucial role of resident pro-inflammatory B and T cells in sustaining tonsillar hypertrophy and hyperplasia by producing TNFα and IL17, respectively, in ex vivo cultures. Additionally, we detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. Furthermore, we evidenced the hypertrophy of germinal centers (GC) and the general hyperplasia of B lymphocytes within the tissue and the lumen of the crypts. Of note, such B cells resulted mainly (IgG/IgM)+ cells, with some IgA+ cells located marginally in the follicles. Finally, by combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work sheds light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization, and opening alternatives of treatment.

Use of anterolateral thigh free flap for reconstruction and salvage of thoracic limb caused by an arteriovenous malformation.

Vascular arteriovenous malformations originate during the early stages of embryonic development and generally grow progressively, especially during adolescence and pregnancy. Limb salvage using microsurgery is presented, in a patient with an arteriovenous malformation who was initially a candidate for limb amputation. En bloc resection of the arteriovenous malformation of all segments with extended brachial approach and the cutaneous component was performed, with an anterolateral thigh free flap for the lateral reconstruction of the hand.

Cloning, comparative sequence analysis and mRNA expression of calcium-transporting genes in horses.

Epithelial calcium transport occurs by paracellular and transcellular mechanisms. Transcellular transport in intestinal and renal epithelia involves several transport proteins, including transient receptor potential vanilloid member 5 (TRPV5), member 6 (TRPV6), calbindin D9k (CB9), calbindin D28k (CB28), sodium calcium exchanger 1 (NCX1), plasma membrane calcium ATPase 1 (PMCA1), and the vitamin D receptor (VDR). We are interested in the horse because of its unique calcium physiology (high blood calcium, high intestinal calcium absorption, high renal excretion of calcium, low vitamin D concentrations), and because horses often have dysregulated calcium balance with various diseases. We cloned the mRNA for equine TRPV5, TRPV6, CB9, CB28, NCX1, PMCA1, and VDR, performed comparative mRNA and protein sequence analysis, and quantified their mRNA expression in the kidney and gastrointestinal tract. Sequence homology for the mRNAs and proteins was high among mammals (>75%), with fish having the lowest homology (<75%). TRPV5, TRPV6, and CB9 expression was higher in the duodenum and proximal jejunum and followed a similar expression pattern. CB28 expression was greatest in the kidney. PMCA1 and NCX1 expression was similar throughout the intestine, but in the kidney PMCA1 expression was higher. Based on our findings, the proximal small intestine is the main site for transcellular calcium transport, with TRPV6 and CB9 serving as the main transport proteins. In the kidney, TRPV6, CB28, and PMCA1 are likely more important. The low VDR expression in the equine small intestine and kidney relative to the large intestine, together with the reported high intestinal absorption and renal excretion of calcium, and low vitamin D concentrations suggests that epithelial calcium transport in horses is not as dependent on vitamin D as in other species.

Evaluation of dynamic testing for pituitary pars intermedia dysfunction diagnosis in donkeys.

BACKGROUND: Endocrine disorders are common in donkeys. Pituitary pars intermedia dysfunction (PPID) is thought to be a frequent disturbance in donkeys due to their longevity. However, information on PPID dynamic testing in donkeys is lacking. OBJECTIVES: The objective of this study was to evaluate the previously described guidelines for PPID diagnosis in horses in donkeys with suspicion of PPID. STUDY DESIGN: Prospective experimental study. METHODS: Eighty donkeys were evaluated for PPID suspicion based on clinical signs and baseline adrenocorticotropic hormone (ACTH) concentrations. Six mix-breed donkeys (one jack and five non-pregnant jennies) fulfilling inclusion criteria were subjected to dexamethasone suppression test (DST), thyrotropin-releasing hormone stimulation test (TRH) and combined DST-TRH challenge. Tests were interpreted according to guidelines for PPID diagnosis in horses. RESULTS: Donkeys fulfilling inclusion criteria were diagnosed with PPID by TRH stimulation test (six of six). Both DST (three of six) and DST-TRH (4/6) challenges failed to detect those animals and showed conflicting results. Similarly, cortisol basal concentrations were not consistent with PPID suspicion. MAIN LIMITATIONS: Characterisation of seasonal and geographical location effect on baseline ACTH concentrations and response to TRH is compelling in this species. Further studies with a larger number of donkeys are needed. CONCLUSIONS: This is the first study in donkeys to evaluate common dynamic tests used for PPID diagnosis in horses. Preliminary results agree with the guidelines for PPID diagnosis in horses and baseline ACTH measurement followed by TRH challenge are recommended tests for diagnosis of PPID in donkeys.

The Mexican consensus on the diagnosis and treatment of diverticular disease of the colon. / Consenso mexicano sobre el diagnóstico y tratamiento de la enfermedad diverticular del colon.

Since the publication of the 2008 guidelines on the diagnosis and treatment of diverticular disease of the colon by the Asociación Mexicana de Gastroenterología, significant advances have been made in the knowledge of that disease. A systematic review of articles published in the medical literature from January 2008 to July 2018 was carried out to revise and update the 2008 guidelines and provide new evidence-based recommendations. All high-quality articles in Spanish and English published within that time frame were included. The final versions of the 43 statements accepted in the three rounds of voting, utilizing the Delphi method, were written, and the quality of evidence and strength of the recommendations were established for each statement, utilizing the GRADE system. The present consensus contains new data on the definition, classification, epidemiology, pathophysiology, and risk factors of diverticular disease of the colon. Special emphasis is given to the usefulness of computed tomography and colonoscopy, as well as to the endoscopic methods for controlling bleeding. Outpatient treatment of uncomplicated diverticulitis is discussed, as well as the role of rifaximin and mesalazine in the management of complicated acute diverticulitis. Both its minimally invasive alternatives and surgical options are described, stressing their indications, limitations, and contraindications. The new statements provide guidelines based on updated scientific evidence. Each statement is discussed, and its quality of evidence and the strength of the recommendation are presented.

Metabolic acidosis inhibits soft tissue calcification in uremic rats.

Metabolic acidosis is common in patients with chronic kidney disease, which is known to affect bone metabolism. We examined the effect of metabolic acidosis on the development of vascular and other soft-tissue calcifications in uremic rats treated with calcitriol. Extraskeletal calcification was measured in vivo, in control rats and rats with a remnant kidney model of uremia with or without ammonium chloride-induced acidosis. Soft-tissue calcification was assessed histologically, by measurement of the expression of the sodium-dependent phosphate cotransporter Pit-1 and by quantification of tissue calcium and phosphorus. Calcitriol administration to uremic rats resulted in significant deposition of material positive for von Kossa stain in the aorta, stomach, and kidney, elevated aortic calcium and phosphorus, increased aortic Pit-1 expression, and high mortality. Calcitriol-treated uremic rats with acidosis did not develop aortic or soft-tissue calcification, did not increase aortic Pit-1 expression, and had significantly lower mortality. Additionally, an acidotic environment prevented calcification of vascular smooth muscle cells in vitro. Our study shows that metabolic acidosis inhibits extraskeletal calcification.

Effects of calcimimetics on extraskeletal calcifications in chronic kidney disease.

While the precise mechanisms of vascular calcification (VC) in chronic kidney disease (CKD) remain to be elucidated, there is a close association between VC and secondary hyperparathyroidism (HPT). The elevations in calcium, phosphorus, the Ca x P product, and parathyroid hormone (PTH) observed in patients with CKD and secondary HPT have been associated with VC and increased risk of cardiovascular morbidity and mortality. We have investigated the development of extraskeletal calcification in uremic rats with secondary HPT treated with vitamin D derivatives (calcitriol or paricalcitol), calcimimetics (R-568 or AMG 641), or the combination of both types drugs. Treatment with calcitriol resulted in a significant increase in the extraosseous calcium and phosphorus content and high mortality. By contrast, treatment with calcimimetics, which provided a better control of plasma PTH levels, did not result in extraskeletal mineral accumulation and did not cause mortality. More important, when added to calcitriol, calcimimetics prevented the development of VC and reduced mortality. Paricalcitol administration to uremic rats resulted in calcification levels and mortality rates that were lower than in rats treated with calcitriol but higher than in rats treated with calcimimetics. The mechanism(s) of action responsible for the anticalcification effect of calcimimetics are likely related to the fact that these drugs can control PTH levels without increasing the plasma Ca x P product. In addition calcimimetic activation of vascular calcium-sensing receptor may also modulate the expression of proteins that prevent the development of VC, like matrix Gla protein.

Effect of intravenous glucose and combined glucose-insulin challenges on energy-regulating hormones concentrations in donkeys.

Metabolic disorders are highly prevalent in donkeys. Differences in energy regulatory hormones and glucose dynamic testing, including the intravenous glucose tolerance test (IVGTT) and combined glucose-insulin test (CGIT), have been documented between donkeys and horses. The aims of this study were to characterise the insulin:glucagon (IGR) and glucagon:insulin (GIR) molar ratios, at baseline and in response to the IVGTT and CGIT in healthy donkeys, and to determine their correlation with endocrine (leptin, ghrelin and adiponectin) and morphometric variables. Median values and interquartile ranges (IQRs) for IGR and GIR in 49 healthy adult donkeys were 1.5 (IQR, 1.0-1.8) and 0.7 (IQR 0.5-0.9), respectively. IVGTT and CGIT were each performed on eight donkeys, while dynamic testing was performed on six donkeys due to loss of two donkeys from the study. IVGTT induced an increase in IGR (and a decrease in GIR) from 15 to 180min after the onset of the test, but had no effect on leptin, adiponectin or ghrelin concentrations. CGIT resulted in a significant elevation in IGR (and a decrease in GIR) from 15 to 120min after the onset of the test. Plasma leptin concentrations increased significantly at 240min. No correlations were found between ratios, hormones and morphometric measurements. The findings support differences between donkeys and horses, which are likely to be related to proportionally higher glucagon compared to insulin concentrations in donkeys, and may be relevant to disorders related to energy dysregulation in donkeys, including metabolic syndrome and dyslipidaemias.