Isolated vascular "v" lesions in liver allografts: How to approach this unusual finding.

According to the Banff criteria for kidney allografts, isolated vascular or "v" lesions are defined as intimal inflammation, age-inappropriate fibro-intimal hyperplasia, or both, without the presence of associated interstitial T cell-mediated rejection (TCMR). In general, these lesions portend a worse outcome for kidney allografts, particularly in those where the "v" lesions are identified in patients with coexistent donor specific antibodies (DSA) or later after transplantation. Although affected arteries are rarely sampled in liver allograft biopsies, we identified nine patients at a mean of 1805 days posttransplantation and compared these to matched controls. Almost half (4 of 9) of the study patient biopsies showed inflammatory arteritis associated with focal or diffuse C4d positivity, which was not observed in matched controls. One "v" lesion patient progressed to rejection-related graft failure and two developed moderate/severe TCMR in subsequent biopsies, whereas only one rejection episode occurred in follow-up biopsies, and no rejection-related deaths or graft failures were detected in controls. In conclusion, patients with liver allograft isolated "v" lesions should undergo further evaluation and closer follow-up for impending TCMR and/or underlying co-existent chronic antibody-mediated rejection (AMR).

Long-term complications according to silicone oil type. A single center cohort study.

PURPOSE: To study the incidence of macular edema (ME), ocular hypertension (OHT), emulsification and migration to the anterior chamber (AC) of silicone oil (SO) in patients after complex retina surgery, stratified by SO type. METHODS: Retrospective, cohort study. Patients who underwent retina surgery with SO injection and extraction in our center were included. We compared the complication rates of ME, OHT, emulsification and migration to the AS according to SO type (1300cSt, 5700cSt and heavy SO). Data on age, sex, emulsification time, duration of the tamponade, previous retina surgeries and diagnosis were also gathered and included in a multivariate analysis. RESULTS: We included 163 patients (mean age of 64.8 years; mean duration of the tamponade: 11 months). Rates of emulsification, ME, OHT and SO migration to the AC were similar in all groups (p = 0.998, 0.668, 0.915 and 0.360). ME was the most frequent complication (33.3-47.8%), which resolved after SO extraction in 77.6% of cases. The majority of cases with OHT persisted (61.7%). Emulsification was related to younger age (OR 0.94) and longer duration of the tamponade (OR 1.04). The odds of SO migration to the AC increased with emulsification (OR 2.78), recurrent retinal detachment (OR 0.99) and aphakia (OR 4.05). CONCLUSIONS: We propose SO extraction as the preferred treatment for ME during SO tamponade. SO extraction should be performed sooner in younger patients to avoid emulsification. In selected patients, we suggest a longer duration of the tamponade up to 11 months with a reasonable safety profile, regardless of the SO type.

Spectrum of gluten-sensitive enteropathy in patients with dysmotility-like dyspepsia.

BACKGROUND: Dysmotility-like dyspepsia symptoms are frequent in patients with gluten-sensitive enteropathy (GSE). Current data suggest that patients with mild enteropathy may be present with gluten-sensitive symptoms and complications. AIM: To investigate the prevalence of GSE, including mild enteropathy, in patients with dysmotility-like dyspepsia symptoms. METHODS: We retrospectively studied 142 patients who presented dysmotility-like dyspepsia symptoms and normal upper gastrointestinal endoscopy. Endoscopic duodenal biopsies were taken and processed using hematoxylin-eosin staining and CD3 immunophenotyping. In patients with enteropathy (number of intraepithelial lymphocytes greater than 25 per 100 enterocytes) we also performed coeliac serology (anti-tissue transglutaminase IgA) and HLA-DQ2/DQ8 genotyping. A gluten-free diet was offered if one of these markers was positive. The final GSE diagnosis was established based on clinical and histopathological response to the gluten-free diet after 18 months of follow-up. RESULTS: Fifty-one patients (35.9%) had enteropathy; 4 (2.8%) Marsh type 3b, 24 (16.9%) Marsh type 3a, 3 (2.1%) Marsh type 2, and 20 (14.1%) Marsh type 1. A positive serology result was extremely low (6.7%) in mild enteropathy (Marsh type 1-3a) in contrast with Marsh type 3b patients (50%). Most patients with enteropathy had positive HLA DQ2 or -DQ8 genotyping (84.1%). Out of the 37 patients who started a gluten-free diet, 34 (91.9%) improved their symptoms, and 28 of 32 (87.5%) had a histopathological or serological response. A final GSE diagnosis was established in 28 of the 142 patients (19.7%). CONCLUSION: Gluten-sensitive enteropathy can be a frequent and unsuspected cause of dysmotility-like dyspepsia.

[Lymphocytic duodenosis: etiological study and clinical presentations]. / Duodenosis linfocítica: estudio etiológico y formas de presentación clínica.

INTRODUCTION: Lymphocytic duodenosis (LD) is a characteristic lesion in the initial phases of celiac disease (CD) but can be associated with many other entities. The aim of this study was to evaluate the prevalence of distinct causes of LD and possible differences in clinical presentation according to etiology. METHODS: A retrospective study was performed that included 194 patients diagnosed with LD (more than 25 intraepithelial lymphocytes per 100 epithelial cells). A preestablished strategy to evaluate the cause of the disease was followed that included celiac serology (antitransglutaminase antibodies), HLA-DQ2/DQ8 genotypes, diagnosis of Helicobacter pylori and small intestinal bacterial overgrowth (SIBO). Diagnosis of CD was established on the basis of clinical and histological response to a gluten-free diet in patients with positive serology or compatible findings on HLA-DQ2 (at least one of the alleles) or -DQ8 (both alleles) study. RESULTS: The most frequent cause of LD was CD (39%), followed by SBBO (22%), H.pylori (14%), CD and SIBO (12%), and other causes (13%). Most of the patients (83%) had a compatible HLA-DQ2 or -DQ8 genotype. In these patients, the most frequent diagnosis was CD (46%), while in the absence of HLA-DQ2/DQ8, the most frequent diagnoses were SIBO (44%) and H. pylori (22%). CD was the most frequent diagnosis in patients referred for dyspepsia, diarrhea and anemia, while H. pylori was the most frequent diagnosis in patients with abdominal pain. CONCLUSIONS: The most common causes of LD in our environment are CD, followed by SIBO and H. pylori infection.

The effect of six-month oral vitamin K supplementation on calcification propensity time in individuals with type 2 diabetes mellitus: A post hoc analysis of a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND AIMS: Experimental studies suggested that vitamin K supplementation may retard arterial calcification. Recently, serum calcification propensity time (T50) has been suggested as a functional biomarker for arterial wall calcification propensity. In this post-hoc analysis of a clinical trial, we evaluated the effect of six-month oral vitamin K supplementation on T50 and assessed the correlation between T50 and imaging arterial calcification parameters in people with type 2 diabetes (T2DM). METHODS: This double-blind, randomized, placebo-controlled trial included 68 participants (age = 69 ± 8 years, 76% male) with T2DM. Participants were assigned to menaquinone-7 (360 µg/day; n = 35) or placebo (n = 33). T50 was measured via nephelometry in serum collected at baseline, three and six months. Arterial calcification was measured at baseline and six months via 18F-Na PET-CT and conventional CT using Target-to-Background ratio (TBR) and Agatston score. Longitudinal analysis of covariance adjusted for baseline T50 was used to study the treatment effect. Spearman's correlation was used to assess the correlation between T50 and imaging calcification parameters. RESULTS: Median baseline T50 was similar in the vitamin K (350 [321-394] minutes) and placebo groups (363 [320-398]). There was no significant difference in T50 between treatment arms over time (ẞ = 1.00, 95%C.I. = 0.94-1.07, p = 0.982). The correlation coefficient of T50 with TBR and Agatston score at baseline were -0.185 (p = 0.156) and -0.121 (p = 0.358), respectively. CONCLUSIONS: No effect of vitamin K supplementation on T50 was observed in T2DM. Moreover, T50 did not correlate with TBR and Agatston score. Further research on vitamin K in arterial calcification and on the validity of T50 as arterial calcification marker is warranted.

Neuropeptide Y expression in cutaneous melanoma.

BACKGROUND: Neuropeptide Y (NPY) is widely found in the nervous system and has a role in numerous physiologic processes. In addition, NPY receptors are expressed in neuroendocrine tumors, breast cancer, prostate cancer, kidney cancer, and some types of sarcomas. Different neuropeptides, particularly α-melanocyte-stimulating hormone (MSH), seem to play a role in the pathogenesis of melanoma. OBJECTIVE: We sought to analyze the expression of NPY in cutaneous melanoma, its association with clinical and histologic features, and its correlation with α-MSH. METHODS: This was an observational study of the immunohistochemical expression of NPY and α-MSH in tissue samples of cutaneous melanomas, different types of melanocytic nevi, and melanoma metastases diagnosed from 2004 to 2008 in San Jorge Hospital, Huesca, Spain. RESULTS: A total of 184 lesions were studied: 49 primary cutaneous melanomas, 12 melanoma metastases (9 cutaneous and 3 lymphatic), and 123 melanocytic nevi. Immunostaining revealed that levels of NPY and α-MSH were significantly higher in melanomas than in melanocytic nevi (P < .001). Melanoma metastases were negative for both neuropeptides. Nodular melanomas showed the highest median percentage of NPY positive cells (75% [20-95]) followed by superficial spreading melanoma (25% [2-92]), whereas lentigo maligna were negative (0% [0-0]). Significant, direct associations between NPY expression and vertical growth (P = .0141) and presence of metastasis (P = .0196) were observed. NPY and α-MSH were positively correlated in cutaneous melanoma (0.49, P < .001). LIMITATIONS: The sample size of melanomas was not very large. CONCLUSION: Our study demonstrates that NPY is significantly expressed in melanomas, especially the nodular type, being associated with invasiveness independently of proliferative markers such as thickness, ulceration, and mitotic index.

[Is there a relationship between cystatin C and inflammatory status, oxidative stress and other cardiovascular risk factors in non-diabetic patients with chronic kidney disease?]. / ¿Existe relación entre los niveles de cistatina C y el estado inflamatorio, el estrés oxidativo y otros factores de riesgo cardiovascular en pacientes no diabéticos con enfermedad renal crónica?

UNLABELLED: Cystatin C is a marker of renal function and a major cardiovascular risk factor. In the general population, cystatin C appears to be influenced by factors other than renal function alone. However, information for serum cystatin C levels in chronic kidney disease (CKD) is lacking. METHODS: We studied 52 nondiabetic patients (38 men, mean age 49 years) with CKD stage 3 (22), 4 (25) or 5 (5) who had measurements of serum cystatin C levels, estimated glomerular filtration rate (MDRD), inflammatory (C-reactive protein, interleukin-6 and fibrinogen), and oxidative markers (anti-oxidized LDL antibodies, serum paraoxonase-1 activity and concentration), left ventricular mass index by echocardiography and other cardiovascular risk factors. RESULTS: Mean cystatin C levels were 2.35 +/- 0.9 mg/l. Cystatin C was positively correlated with creatinine serum levels, estimated glomerular filtration rate, PTH levels and negatively with anti-oxidized LDL antibodies. On the other hand, cystatin C was not related to inflammatory markers, serum paraoxonase-1 activity and concentration, proteinuria, HDL or LDL cholesterol, serum triglycerides, left ventricular mass index or demographic factors such as age, body mass index and blood pressure. After adjustment for PTH levels and anti- oxidized LDL antibodies, only estimated glomerular filtration rate was independently related serum cystatin C levels (beta = -0.500, p = 0.001). CONCLUSION: In nondiabetic patients with CKD, cystatin C is closely related to the degree of renal dysfunction. In contrast, inflammatory state, oxidative stress, left ventricular mass index and other cardiovascular risk factors are not related to cystatin C levels in this population.

Lateral communication by fast proton conduction: a model membrane study.

Lateral communication of information along biological membranes is thought to be a key process for many cellular activities. Support for this hypothesis comes from physicochemical experiments that show that an efficient facilitated lateral proton conduction exists along lipid-water interfaces. The existence of a local two-dimensional hydrogen bond network between the lipid headgroups and their associated water molecules would explain this phenomenon.

Rapid analytical method for the determination of organic and inorganic species in tomato samples through HPLC-ICP-AES coupling.

A HPLC-inductively coupled plasma atomic emission spectrometer (ICP-AES) hyphenation technique was used to determine the concentration of some organic (i.e., carbohydrates, carboxylic acids) as well as inorganic (metals and anions) compounds in tomato samples. A high efficiency nebulizer (HEN) coupled to a low inner volume cyclonic spray chamber (Cinnabar) was used to interface both techniques. The HPLC-ICP-AES chromatograms for organic compounds were obtained by plotting the 193.03nm carbon emission intensity versus time. In the present work, it was also possible to obtain information about the concentration of several metals in foodstuffs. Finally, by registering the intensity at the sulphur and phosphorous emission wavelengths, the content of anions such as sulphate and phosphate was determined. In general terms, the results obtained with HPLC-ICP-AES did not differ significantly from those found with a refractive index detector. Due to the huge amount of information provided by this hyphenation, it was possible to apply it to the discrimination among different samples of native tomato cultivars.

Primary pure squamous cell carcinoma of the breast diagnosed by fine-needle aspiration cytology: a case study using liquid-based cytology.

Pure primary squamous cell carcinoma (SCC) is an extremely rare type of breast tumor. We report one of such cases in a 32-year-old woman, diagnosed by fine-needle aspiration cytology (FNAC). Aspiration smears were characterized by squamous cells, both isolated and in aggregates, at various stages of maturation. The tumor was excised, and the histologic sections confirmed the cytologic diagnosis. Pure primary SCC of the breast has a distinctive cytomorphologic appearance, and diagnosis of this tumor by FNAC is possible. For its diagnosis, the exclusion of SCC of local cutaneous structures and metastasis of distant squamous carcinoma are mandatory.

Proton lateral conduction along a lipid monolayer spread on a physiological subphase.

A localized lateral proton pathway is present along the phospholipid polar heads and bound water molecules when the lipids are spread in monolayers at the air/water interface. Conduction can be detected on concentrated buffers as found under physiological conditions if the lateral proton gradient is large enough. The localized movement supports the occurrence of microlocalized proton circuits along a membrane and of lateral proton gradients.

Use of a fluorescein derivative of phosphatidylethanolamine as a pH probe at water/lipid interfaces.

A fluorescent indicator for the determination of pH in the vicinity of water/lipid interfaces was produced by the covalent linkage of fluoresceinisothiocyanate to Escherichia coli phosphatidylethanolamine. When embedded in monolayers spread on an air/water interface, its apparent pK was shown to be only slightly affected by the nature of the polar headgroups or the packing density of the host phospholipids. Its properties were not affected by the ion content of the subphase. For small unilamellar vesicles, its properties were only affected when localized in the inner layer. This probe could therefore be of value in the study of proton fluxes along biological membranes.

Adjuvant lipopeptide interaction with model membranes.

The cationic lipohexapeptide Pam3Cys-Ser-(Lys)4 is a synthetic model for the triacylated N-terminal part of bacterial lipoproteins, and it is used as an adjuvant and macrophage activator. The amphiphilic lipopeptide was injected below a phosphatidylserine monolayer at the air-water interface. It interacted with the interface, as seen by a decrease in the surface potential (deltaV), and it was inserted in the monolayer, until surface charge neutralization was reached, as seen by the parallel increases of deltaV and of the surface pressure. No insertion occurred above 29 mN/m. The interaction kinetics was sensitive to ionic strength and to the nature of acidic phospholipids and of their acyl chains, but the final equilibrium was independent of these factors. Addition of the lipopeptide to large unilamellar vesicles (LUVs) induced their aggregation, and an exchange of lipids between fluorophor-labelled and non-labelled LUVs. However, no fusion was observed, just as reported for polylysine. The lipopeptide strongly inhibited calcium-induced fusion of PS LUVs, in contrast to the published effect of polylysine. This was probably due to inhibition of calcium fixation on liposomes, since it was observed that the lipopeptide efficiently displaced 45Ca2+ from a PS monolayer. In addition, a phospholipid segregation was observed in SUVs for a few ten micromolar of the lipopeptide.

[Portal-splenic-mesenteric venous thrombosis secondary to a mutation of the prothrombin gene]. / Trombosis venosa portoesplenomesaraica secundaria a mutación del gen de la protrombina.

Thrombosis of the portal-mesenteric axis is an infrequent cause of intestinal ischemia or infarction. In addition to the multiple acquired factors that contribute to the development of this entity, hereditary risk factors, especially the factor V Leiden mutation and the G20210A mutation of the prothrombin gene, have been implicated. The G20210A mutation of the prothrombin gene is found in up to 40% of patients with splenic-portal-mesenteric thrombosis. The present case illustrates the unusual and nonspecific presentation of this mutation in the form of diarrhea and images of thrombosis of the superior mesenteric-portal vein and cavernous transformation of the portal vein. Delayed diagnosis is highly frequent since the clinical signs, laboratory investigations and radiological tests do not suggest the diagnosis. The patient received anticoagulant treatment and showed clinical improvement with complete portal-mesenteric recanalization. Currently the diagnostic technique of choice is magnetic resonance angiography or computerized tomography angiography and treatment consists of indefinite anticoagulation. This case illustrates that an unusual or atypical localization of venous thrombosis may be a manifestation of thrombophilia, emphasizing the importance of genetic screening in these cases.

[Prevalence of diabetic retinopathy in the region of Girona. Study of related factors]. / Prevalencia de la retinopatía diabética en la población de diabéticos diagnosticados en las comarcas de Girona. Estudio de los factores asociados.

PURPOSE: To determine of the prevalence of diabetic retinopathy in the general diabetic population in the Girona region and epidemiologic study of the related factors. METHODS: A population-based cross-sectional study of a randomised sample taken of 401 diabetics in the Girona region. Descriptive statistical analysis of the ocular lesions in relation to diabetic retinopathy and analysis of logistic regression in order to determine the related factors. RESULTS: 30.6% (IC 95%: 26.5-35.5) of the sample presented some degree of diabetic retinopathy, 19.4% (IC 95%: 15.4-24.0) at the initial stage, 8.4% (IC 95%: 5.8-1.9) pre-proliferative and 2.6% (IC 95%: 1.3-5.1) at a proliferative stage. Regarding the type of diabetes, 53% of the patients with type 1 diabetes and 34.2% of those with type 2 diabetes had retinopathy. Retinopathy was observed in 15.7% of diabetics with less than 10 years of diabetes evolution, 51.3% in those between 10 and 20 years and 62.8% in those with more than 20 years. The concentration of HbA1C was significantly associated with the degree of retinopathy. Of those patients with retinopathy, 60.3% were insulin-treated, 30.6% with oral hypoglucemiants and 10.3% on diet only. Patients with family antecedents of retinopathy presented a prevalence three times greater than those without. CONCLUSIONS: Approximately one in three diabetic patients exhibited some degree of retinopathy in this study dealing with a population-based cohort of diabetic patients in Spain. The prevalence was greater among type I diabetic patients. As expected, years of evolution of the disease, type of treatment and diabetic metabolic control were the most significant factors influencing the presence of retinopathy.

Pectus excavatum, manejo mínimamente invasivo con técnica de Nuss: experiencia Instituto Nacional del Tórax / Pectus excavatum, minimally invasive management with Nuss technique

Resumen Objetivo Comunicar la experiencia en el tratamiento de pectus excavatum en el Instituto Nacional del Tórax. Material y Método: Estudio descriptivo con seguimiento. Se recolectaron datos de las variables de interés, mediante la revisión de fichas clínicas. Se incluyeron pacientes operados entre marzo de 2007 y abril de 2018. Resultados Se incluyeron 86 pacientes operados con técnica mínimamente invasiva en el período descrito. De ellos, 74 pacientes de sexo masculino. El promedio de edad al momento de la cirugía fue de 17,8 años. El principal motivo de consulta fue por desmedro estético que correspondió al 41,8% de los pacientes. Salvo en 1 paciente, en todo el resto se ocupó una sola barra. En nuestra serie hubo 12 pacientes que presentaron alguna complicación operatoria y 1 paciente fallecido. Hasta el cierre del seguimiento se retiraron 61 barras, 2 de ellas previo al período estipulado de tratamiento, por morbilidad. Hay 20 barras in situ y 4 pacientes de los cuales no se tiene registro por abandono de controles. Discusión El pectus excavatum es la más frecuente de las deformidades de la pared torácica, es 4 a 6 veces más frecuente en hombres que en mujeres. En general los pacientes son asintomáticos, aunque algunos pueden presentar síntomas cardiopulmonares. La reparación con cirugía mínimamente invasiva con técnica de Nuss aparece hoy en día como el gold standard de manejo. Conclusión El manejo de los pacientes con pectus excavatum en nuestra Institución se asemeja a lo reportado en la literatura internacional. Nuestros esfuerzos deben apuntar a disminuir la morbimortalidad asociada.

Aim To communicate the experience in the treatment of pectus excavatum in the National Institute of Thorax. Materials and Method: Descriptive study with follow-up. Data of variables of interest were collected through the review of clinical records. Patients operated between March 2007 and April 2018 were included. Results 86 patients operated with the Nuss technique were included in the period described. Of them, 74 male patients. The average age at the time of surgery was 17.8 years. The main reason for consultation was due to cosmetic detriment that corresponded to 41.8% of the patients. Except in 1 patient, in all the rest a single bar was occupied. In our series, there were 12 patients who presented some operative complication and 1 patient died. Up to the end of the follow-up, 61 bars were removed, 2 of them in non-scheduled surgery. There are 20 bars in situ and 4 patients of which there is no registration due to abandonment of controls. Discussion Pectus excavatum is the most frequent of the deformities of the chest wall, it is 4 to 6 times more frequent in men than in women. In general, patients are asymptomatic, although some may have cardiopulmonary symptoms. The repair with minimally invasive surgery with Nuss technique appears today as the goldstandard of management. Conclusion The management of patients with pectus excavatum in our Institution is similar to that reported in the international literature. Our efforts should aim to reduce the associated morbidity and mortality.

Mycobacterial glycopeptidolipid interactions with membranes: a monolayer study.

Mycobacterial glycopeptidolipid (GPL) interactions with membranes were analysed with monolayer experiment, using GPLs bearing 3, 1, or 0 carbohydrate residues (GPL3, GPL1, GPL0). Compression isotherms and surface potential determinations suggested that the glycopeptidic moiety of GPL3 permanently dipped in water, while those of GPL1 and GPL0 can lay in the interface. Insertion of GPL molecules into a preformed phospholipid monolayer was observed using GPL3 or GPL1 dispersions, but not from GPL0. It is postulated that the activity of GPL0 is low due to its failure to become inserted into membranes, as is that of GPL3 owing to its insertion only by its acyl chain. GPL1 is likely to disturb membranes by inserting its glycopeptidic moiety into the interface.

Lateral proton conduction along a lipid-water interface layer: a molecular mechanism for the role of hydration water molecules.

Using a fluorescence method applied to phospholipids spread at the air-water interface, we showed the occurrence of a localized proton pathway along the phospholipid polar heads. From the systematic investigation of this phenomenon, we conclude that the protons diffuse through a hydrogen bond network which is a matrix of hydrated polar head groups.