Fecal microbiota transplantation in hepatic encephalopathy : a review of the current evidence and future perspectives.

Hepatic encephalopathy (HE) is a leading cause of hospitalization and morbimortality in advanced cirrhosis with limited therapeutic options available. Given the paramount role of gut microbiota in HE, and the efficacy of fecal microbiota transplantation (FMT) in other diseases, this review intends to summarize the evidence supporting the safety, efficacy and future perspectives of FMT in HE. Current evidence, despite being scarce, points towards FMT being a safe, effective and tolerable procedure in HE. Some unanswered questions remain about the optimal dose, the administration route, the long term effects and the selection of the optimal donor. Future trials, some of which are already underway, will provide us additional evidence and hopefully the necessary answers.

Evaluation of the sensitivity of the Express View function in the Mirocam® capsule endoscopy software.

Background: A new computer algorithm called Express-View has recently been introduced by Mirocam, but data concerning its application and efficacy are scarce.Objective: To evaluate the lesion detection rate, per-patient sensitivity and the diagnostic accuracy using Express-View.Methods: All patients who performed CE between January 2018 and June 2019, whose indication was obscure gastrointestinal bleeding (OGIB) and with findings on CE, were included. Lesions identified in conventional reading were selected and considered as reference.Results: Eighty-nine patients were included, 50.6% male, with a mean age of 68.4 years-old (±12.3). The Express-View mode detected 85.5% of lesions previously detected by conventional reading (524 out of 613). There were 89 missed lesions, mainly erosions or ulcers (44.9%) and angioectasias (38.2%). The lesion detection rate was found to be lower in the jejunum and ileum compared to extra-small bowel locations and duodenum (p = .04). Although Express-View had a per-patient sensitivity for all lesions of 56.2% and a per-patient sensitivity for all clinically significant lesions of 83.1%, it achieved a diagnostic accuracy of 91%.Conclusions: The per-patient sensitivity for all lesions was shown to be below expectations, although the lesion detection rate, the per-patient sensitivity for all clinically significant lesions, and the diagnostic accuracy were shown to be higher.

Influence of collagen cross-linkers addition in phosphoric acid on dentin biomodification and bonding of an etch-and-rinse adhesive.

OBJECTIVE: To investigate the effects of natural collagen cross-linkers incorporation in phosphoric acid etchant on dentin biomodification, microtensile bond strength (µTBS) and nanoleakage (NL) of a two-step etch-and-rinse adhesive. METHODS: Experimental aqueous solution of 37% ortho-phosphoric acid were prepared with the addition of 2% biomodification agents: Lignin (LIG) from industrial paper production residue, Cardanol (CARD) from cashew-nut shell liquid, and Proanthocyanidin (PAC) from grape-seed extract. Negative control (NC) was acid solution without cross-linker whilst commercial control (CC) was Condac 37 gel (FGM). Dentin specimens were assayed by FTIR after 15s etching to detect collagen cross-linking. Extracted third molars were used for µTBS (n=7) and fracture mode analysis of Optibond S (Kerr), tested after 24h or 1000 thermal cycles. NL was surveyed by SEM. Statistical analysis was performed with two-way ANOVA and Tukey's test (p<0.05). RESULTS: FTIR confirmed cross-linking for all agents. µTBS of CC was the highest (46.6±6.2MPa), but reduced significantly after aging (35.7±5.2MPa) (p<0.001). LIG (30.6±3.7MPa) and CARD (28.3±1.8MPa) attained similar µTBS which were stable after aging (p>0.05). Fracture mode was predominantly adhesive. At 24h, all groups showed presence of silver uptake in hybrid layer, except CARD. After aging, CARD- and LIG-treated specimens exhibited little amount of silver penetration. CC, PAC and NC showed gaps, great nanoleakage at hybrid layer and presence of water channels in adhesive layer. SIGNIFICANCE: Altogether, ortho-phosphoric acid incorporated with LIG and CARD promotes stable resin-dentin bond strength with minor nanoleakage after aging, thereby achieving therapeutic impact without additional clinical steps.

The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes.

BACKGROUND: Interindividual variability in response to aspirin has been popularized as 'resistance'. We hypothesized that faster recovery of platelet cyclooxygenase-1 activity may explain incomplete thromboxane (TX) inhibition during the 24-h dosing interval. OBJECTIVE: To characterize the kinetics and determinants of platelet cyclooxygenase-1 recovery in aspirin-treated diabetic and non-diabetic patients. PATIENTS/METHODS: One hundred type 2 diabetic and 73 non-diabetic patients on chronic aspirin 100 mg daily were studied. Serum TXB(2) was measured every 3 h, between 12 and 24 h after a witnessed aspirin intake, to characterize the kinetics of platelet cyclooxygenase-1 recovery. Patients with the fastest TXB(2) recovery were randomized to aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily, for 28 days and TXB(2) recovery was reassessed. RESULTS AND CONCLUSIONS: Platelet TXB(2) production was profoundly suppressed at 12 h in both groups. Serum TXB(2) recovered linearly, with a large interindividual variability in slope. Diabetic patients in the third tertile of recovery slopes (≥ 0.10 ng mL(-1) h(-1) ) showed significantly higher mean platelet volume and body mass index, and younger age. Higher body weight was the only independent predictor of a faster recovery in non-diabetics. Aspirin 100 mg twice daily completely reversed the abnormal TXB(2) recovery in both groups. Interindividual variability in the recovery of platelet cyclooxygenase activity during the dosing interval may limit the duration of the antiplatelet effect of low-dose aspirin in patients with and without diabetes. Inadequate thromboxane inhibition can be easily measured and corrected by a twice daily regimen.

Un reto en reconstrucción mamaria / A challenge in breast reconstruction

La reconstrucción mamaria ha evolucionado en estos últimos años con la aparición de novedades como la infiltración de grasa autóloga y el uso de matrices dérmicas. Presentamos un caso complejo de reconstrucción mamaria tras el fracaso de la cirugía primaria. Analizamos las diversas técnicas quirúrgicas llevadas a cabo en este caso, con las que consideramos que debería estar familiarizado el cirujano que lleva a cabo la reconstrucción de la mama. El autotrasplante de grasa permite minimizar los efectos locales de la radioterapia y engrosar los tejidos. Las matrices dérmicas acelulares proporcionan una cobertura extra del polo inferior del implante y garantizan una expansión más segura. En ocasiones, técnicas quirúrgicas sencillas permiten rescatar procesos complicados con mínima morbilidad y escaso sacrificio tisular (AU)

Breast reconstruction has been in evolution in the last few years with the appearance of new techniques like autologous fat grafting and a cellular dermal matrix. We present a complex case of breast reconstruction after the failure of the first surgery. We analyze the different performed techniques, that should be familiar for all breast surgeons. Lipofilling allows minimize the local effects of radiotherapy and make tissues thicker. A cellular dermal matrix makes possible an extra coverage of the lower pole of the breast implant and guarantees safer expansion. Sometimes, simple surgical techniques allow rescue complicated cases with low morbidity and less tissue sacrifice (AU)

Successful bone marrow transplantation reveals the lack of endothelial progenitor cells mobilization in a patient with critical limb ischemia: a case report.

Restoring blood flow to ischemic tissue is a prerequisite for treatment of ischemic diseases. Cell-based therapy based on bone marrow transplantation is a promising option for patients with critical limb ischemia (CLI). The efficacy of cell therapies to augment neovascularization seems to involve endothelial progenitor cells (EPCs); however, the mechanisms underlying the efficacy have not been fully elucidated. Herein we have described the case of a young patient with severe CLI, who experienced a 24-month beneficial clinical response to autologous bone marrow transplantation. The exceptional amelioration enabled him to perform standardized maximal treadmill exercise test that demonstrated lack of exercise-induced EPC mobilization, despite adequate stromal-derived factor 1 and vascular endothelial growth factor responses. Therefore, tissue ischemia is not sufficient to promote the recruitment of EPCs that have been demonstrated to be involved in the recovery from ischemia. The local implantation of marrow-derived elements may provide cells and/or trophic factors, which have the capacity to augment angiogenesis, opening new approaches to the etiopathogenesis of the disease.

A new freezing and storage procedure improves safety and viability of haematopoietic stem cells and neutrophil engraftment: a single institution experience.

BACKGROUND AND OBJECTIVES: Autologous peripheral blood stem cell transplantation has recently become a standard therapeutic approach to virus-related or infected haematological malignancies. Collection, manipulation, storage and thawing of leukapheresis products in this subset of patients require strict monitoring to prevent infection risk for operators and risk of contamination for other stored bags. MATERIALS AND METHODS: This is a non-randomized retrospective observational study. In the 2000-2002 period, a single bag freezing procedure was used for autologous peripheral blood stem cell transplantation. Bags were stored in tanks containing liquid and gas phase nitrogen. In 2002, the processing procedure was revised, and a second additional safety bag and a new storage tank containing jacketed liquid nitrogen have been used. RESULTS: A total of 524 bags were thawed, of which 121 processed with the single bag method and 403 with the double bag method. Forty-nine and 109 patients were infused respectively. The observed rupture rate with the single bag in liquid and gas phase nitrogen was 17 and 2.5%, respectively, against a rupture rate as little as 0.24% with the new methodology. Viability revealed levels of 84.4% +/- 6.1% and 96.9% +/- 2.4% for the single and double-bag respectively. This statistically significant (P < 0.0001) difference correlated with better neutrophil engraftment. CONCLUSIONS: The new proposed method, based on a double bag and storage freezer without liquid or gas phase nitrogen into a cryogenic chamber, significantly reduces bag rupture and bio-hazard and improves stem cell viability and neutrophil engraftment remarkably.

A new HLA-A*680106 allele identified in individuals with celiac disease from the Friuli area of northeast Italy.

A novel human leukocyte antigen (HLA)-A*680106 antigen was identified in two Italian individuals by polymerase chain reaction sequencing-based typing.

Proteins specifically hyperexpressed in a coeliac disease patient with aberrant T cells.

An aberrant T cell population is the basis for diagnosis of refractory coeliac disease and determines the risk of enteropathy-associated T cell lymphoma. This disease is serious with a poor survival. Pathogenetic mechanisms sustaining aberrant T cell proliferation remain unknown. Recently, alemtuzumab has been proposed as a promising new approach to treat these patients. Only few single cases have been tested at present; nevertheless, in all the cases a clinical improvement was observed. However, whether intraepithelial lymphocytes have been targeted effectively by alemtuzumab is still debated. This study reports, using two-dimensional difference gel electrophoresis (2D DIGE), hyperexpressed proteins associated specifically with aberrant T cells found in a patient with coeliac disease by comparison of the protein expression of this sample with that of patients with coeliac disease and polyclonal T cells or with control subjects. The data demonstrated a significantly higher expression of IgM, apolipoprotein C-III and Charcot-Leyden crystal proteins in a duodenal biopsy specimen of the patient with clonal T cells compared with that of other patients. These preliminary results allow hypothesizing different clinical effects of alemtuzumab in patients with coeliac disease and aberrant T cell proliferation, because as well as the probable effect on T cells, alemtuzumab could exert its effect by acting on inflammatory associated CD52(+) IgM(+) B cells and eosinophil cells, known to produce IgM and Charcot-Leyden crystal proteins, that we demonstrated to be altered in this patient. The results also emphasize the possible association of apolipoprotein with aberrant T cell proliferation.

Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control.

AIMS/HYPOTHESIS: Inflammation plays a pathogenic role in the development of accelerated atherosclerosis in diabetes. Soluble CD40 ligand (sCD40L) is enhanced in diabetes; however, the molecular mechanisms linking sCD40L to accelerated atherosclerosis in diabetes are still unclear. We tested the hypothesis that sCD40L may be involved in the vascular complications in diabetes and exerts its effect by triggering inflammatory reactions on mononuclear and endothelial cells (ECs). METHODS: We studied 70 patients, 40 with type 2 and 30 with type 1 diabetes, with a history or physical examination negative for cardiovascular disease, and 40 non-diabetic and 30 healthy subjects, matched with the type 2 and type 1 diabetic patients, respectively. Plasma and serum sCD40L, and plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin and monocyte chemo-attractant protein-1 (MCP-1) were measured. Adhesion molecules and MCP-1 release, the ability to repair an injury in ECs, and O2- generation in monocytes were analysed in vitro after stimulation with serum from patients or controls. RESULTS: Type 2 and type 1 diabetic patients had significantly higher sCD40L levels than controls. Furthermore, high sCD40L was associated with in vitro adhesion molecules and MCP-1 release, impaired migration in ECs and enhanced O2- generation in monocytes. Improved metabolic control was associated with a reduction of plasma sCD40L by 37.5% in 12 type 1 diabetic patients. Furthermore, elevated sCD40L in diabetic patients was significantly correlated with HbA1c levels. CONCLUSIONS/INTERPRETATION: Upregulation of sCD40L as a consequence of persistent hyperglycaemia in diabetic patients results in EC activation and monocyte recruitment to the arterial wall, possibly contributing to accelerated atherosclerosis development in diabetes.

Pre-storage leucocyte depletion and transfusion reaction rates in cancer patients.

Passenger leucocytes transfused with allogenic blood are responsible for potential adverse effects. The impact of pre-storage leucodepletion (in-line filtration) of all whole blood units on transfusion reaction rate among patients suffering from cancer was retrospectively studied, comparing all reactions following red blood cell (RBC) transfusions during 2 years of pre-storage vs. 2 years of selective (bedside) leucodepletion. During selective leucodepletion, 5165 RBC units - of which 2745 were bedside filtered units- were transfused to 866 patients. Twenty-eight reactions were recorded: 22 (15 in the bedside group) febrile non-haemolytic transfusion reactions (FNHTR) and six allergic reactions (five in the bedside group). The overall percentage of reactions was 0.54 (0.76 for bedside) and 0.42 for FNHTR (0.54 for bedside). During pre-storage leucodepletion, 4116 RBC units were transfused to 841 patients. Eleven reactions were recorded: four FNHTR and seven allergic reactions (urticaria). The percentage of reactions for transfused RBC units was 0.26 (0.09 for FNHTR). Comparison between pre-storage filtration and bedside filtration with regard to FNHTR showed an odds ratio of 2.80 (95% confidence interval = 0.83-14.87) for bedside filtration. The study suggests that, for transfused patients affected by cancer, pre-storage leucodepletion is more effective than selective (bedside) filtration in reducing the incidence of transfusion reactions (FNHTR).

Efficacy of mometasone furoate microemulsion in the treatment of erosive-ulcerative oral lichen planus: pilot study.

BACKGROUND: Oral lichen planus (OLP) is a frequent immunological chronic disease, having different clinical forms: asymptomatic and symptomatic. Symptomatic OLP has been palliated with topical corticosteroids with different levels of efficacy and safety. The purpose of this pilot phase II clinical trial was to determine the efficacy of mometasone furoate microemulsion upon the symptoms and signs of erosive-ulcerative OLP. METHODS: Forty-nine patients with clinical and histologically confirmed erosive-ulcerative OLP were enrolled in this study (36 women and 13 men). Their average age was 56.4 years (from 28 to 78). The treatment consisted of 0.1% mometasone furoate microemulsion mouthwash three times a day over 30 days. Pain, erythema and ulceration were assessed after 15 and 30 days of treatment. The data was processed and statistically analysed by student's t-test for paired samples. RESULTS: Mometasone caused a statistically significant reduction in pain (3.58 vs. 0.65, P = 0.0000). Treatment significantly reduced the surface area of erythema (155.2 vs. 21.9 mm(2), P = 0.0001) and ulceration (30.7 vs. 7.3 mm(2), P = 0.0000). None of these patients suffered severe adverse effects. CONCLUSIONS: Mometasone furoate microemulsion is a safe and effective therapy in the treatment of symptomatic erosive-ulcerative OLP.

In COPD patients, body weight excess can mask lean tissue depletion: a simple method of estimation.

Although a great number of studies have been carried out on the relationship between chronic obstructive pulmonary disease (COPD) and low body weight, the identification of the most suitable warning signs of this wasting condition is still under debate. It has been indicated in earlier studies that body weight alone is of limited diagnostic value concerning this clinical condition in as far as a great number of COPD patients are usually overweight. For this reason, the aim of the current research was to find parameters that take into consideration the fact that body composition should be taken into account instead of weight only, and to assess whether COPD can be considered a "protein wasting disease", defining sensitive and significant indices of lean tissue depletion in relationship to the severity of the clinical symptoms. One hundred and seventy-five stable COPD outpatients with differing degrees of bronchial obstruction and arterial blood gas abnormalities were consecutively recruited: anthropometric measurements and body composition analysis were carried out; 60 healthy subjects with normal pulmonary function, matched for sex, age and anthropometric parameters, were considered as controls. The data obtained showed a lower prevalence (9%) of underweight COPD patients in comparison with normal weight (37%) and overweight (54%) patients. In COPD patients, the phase angle measured by bioelectrical impedance analysis, whose deterioration is a good indicator of protein mass depletion, was altered by 19%, thus allowing the identification of currently malnourished subjects included in the overweight COPD patients group. In addition, significant correlations (p = 0.000) were found between the same nutritional variable, respiratory function and gas-exchange parameters, thus confirming that the more severe the stage of the pulmonary disease, the higher the degree of protein breakdown, regardless of body weight.

Cita telefónica automatizada. Soluciones precisas a un problema concreto en el Área 1 de atención primaria de Madrid

El Área 1 de Atención Primaria de Madrid ha presentado sus primeras conclusiones del plan piloto previsto para dotar a los centros de salud de un dispositivo automático de cita previa ensayado en el Centro de Salud La Paz de Rivas Vaciamadrid. Objetivo del proyecto: Facilitar el acceso telefónico para la obtención de cita a través de un sistema automático, disminuyendo las reclamaciones derivadas del mismo y aumentar, de esta forma, la satisfacción del usuario con la cita previa. Descripción de la experiencia: Se han instalado 5 líneas telefónicas para asignación de cita previa automática con reconocimiento fonético y a través de tonos, que permiten la gestión inteligente de llamadas incluyendo el desvío a operadoras humanas. Las exigencias técnicas específicas son las referidas a las características de la centralita del centro que debe ser de multifrecuencia, informatización de las bases de datos de pacientes, software y hardware de reconocimiento fonético. Resultados: Se ha obtenido un porcentaje de cita estabilizado entre un 36,10 y un 52,20 por ciento a los 8 meses desde el inicio. Al año de la implantación, de aquellos pacientes que solicitan cita a través del teléfono, la media de citas telefónicas registradas es de un 44 por ciento. Dado que el sistema funciona 24 h al día, 365 días al año, se están produciendo un 10,11 por ciento de llamadas fuera de horario de apertura del centro, citándose el 55 por ciento de las mismas. Conclusiones: La cita telefónica automática permite, con eficiencia y eficacia, la gestión de llamadas para cita previa, aumentando la capacidad de respuesta, fundamentalmente, en los picos horarios y la distribución de llamadas hacia los horarios de cierre del centro (AU)

Fetal vibro-acoustic stimulation with a can--a clinical study.

OBJECTIVE: To assess the usefulness of the can as a fetal vibro-acoustic stimulator in the clinical environment. PATIENTS AND SETTING: 112 high-risk obstetric patients at Coronation Hospital, Johannesburg. METHOD: 161 vibro-acoustic stimulation tests with a can and 159 non-stress tests (NSTs) were performed. The results of the can test were compared with those of the NSTs and with fetal outcome at delivery. RESULTS: The can test showed poor sensitivity (5/9). Three of the 4 false-negative results were due to placental abruption that occurred subsequent to the can test. The ability of the can test to predict a reactive NST and good fetal outcome was 94% (negative predictive value). CONCLUSIONS: In view of the reasonable negative predictive value, the test should be evaluated further as a screening test at primary care level, where there are few or no cardiotocographic facilities.