Cardiac resynchronization therapy: gender related differences in left ventricular reverse remodeling

AIM: Gender related differences in epidemiology, treatment, and prognosis of heart failure (HF) have been reported. We examined the sex influence in patients treated with cardiac resynchronization therapy (CRT). METHODS AND RESULTS: Out of 334 consecutive HF patients (19.7% women) who underwent CRT, 195 patients reached clinical and echocardiographic evaluation at six and 12 months and were selected for analysis. A reduction in left ventricular (LV) end-diastolic volume/m(2) (EDVi) and end systolic volume/m(2) (ESVi) was evident in the overall population at six months (P < 0.001) and from six to 12 months (P < 0.001). Compared to men, women showed significantly greater changes in LV volumes at mid (P < 0.05) and long-term (P < 0.001) follow-up and a significantly higher LV ejection fraction (EF) (40.8 +/- 12.3 vs 34.1 +/- 10.1, P < 0.01) at one year. Multiple regression analysis, including several demographic and clinical parameters, revealed that female gender is independently associated with greater reduction in LV ESVi. At the 12-month follow-up, the proportion of responders (defined in terms of ESV reduction by at least 10%) was higher in women than in men (76.1% vs 59.3%, P < 0.05). CONCLUSIONS: CRT induced a gender specific LV remodeling response.     

Lentiviral vector-mediated gene transfer in T cells from Wiskott-Aldrich syndrome patients leads to functional correction.

Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency with a median survival below the age of 20 due to infections, severe hemorrhage, and lymphomas. Transplantation of hematopoietic stem cells from HLA-identical sibling donors is a resolutive treatment, but is available for a minority of patients. Transplantation of genetically corrected autologous hematopoietic stem cells or T cells could represent an alternative treatment applicable to all patients. We investigated whether WAS gene transfer with MMLV-based oncoretroviral and HIV-based lentiviral vectors could restore normal functions of patients' T cells. T cells transduced either with lentiviral vectors expressing the WAS protein (WASP) from the ubiquitous PGK promoter or the tissue-specific WASP promoter or with an oncoretroviral vector expressing WASP from the LTR, reached normal levels of WASP with correction of functional defects, including proliferation, IL-2 production, and lipid raft upregulation. Lentiviral vectors transduced T cells from WAS patients at higher rates, compared to oncoretroviral vectors, and efficiently transduced both activated and naive WAS T cells. Furthermore, a selective growth advantage of T cells corrected with the lentiviral vectors was demonstrated. The observation that lentiviral vector-mediated gene transfer results in correction of T cell defects in vitro supports their application for gene therapy in WAS patients.     

Classificazione,inquadramento diagnostico e trattamento della lesione di Monteggia in età pediatrica

LO SCALPELLO-OTODI Educational - Monteggia fractures represent the association of a fracture of the proximal ulna and luxation of the radial head. This type of lesion is infrequent and may be...     

Production of polyacrylamide gradient gel for lipoprotein electrophoretic separation

BACKGROUND: Small LDL are associated with risk of coronary heart disease. Gradient gel electrophoresis for LDL separation is not a simple method and high-quality non-denaturing gradient gels are lacking. METHODS: In this paper, we describe a method for the preparation of a polyacrylamide gel system that consists of an upper linear gradient gel (1.8-10%) and a lower homogeneous gel (16%) for the determination of LDL size. RESULTS: The linear gradient is highly reproducible. Intra-inter gel coefficients of variation for LDL particle size are lower than 0.6%. CONCLUSION: Effective LDL size measurement from pre-stained serum samples is possible in a stable gel.     

Early Versus Delayed Source Control in Open Abdomen Management for Severe Intra-abdominal Infections: A Retrospective Analysis on 111 Cases

Background

Time to source control plays a determinant prognostic role in patients having severe intra-abdominal infections (IAIs). Open abdomen (OA) management became an effective treatment option for peritonitis. Aim of this study was to analyze the correlation between time to source control and outcome in patients presenting with abdominal sepsis and treated by OA.

Methods

We retrospectively analyzed 111 patients affected by abdominal sepsis and treated with OA from May 2007 to May 2015. Patients were classified according to time interval from first patient evaluation to source control. The end points were intra-hospital mortality and primary fascial closure rate.

Results

The in-hospital mortality rate was 21.6% (24/111), and the primary fascial closure rate was 90.9% (101/111). A time to source control ≥6 h resulted significantly associated with a poor prognosis and a lower fascial closure rate (mortality 27.0 vs 9.0%, p = 0.04; primary fascial closure 86 vs 100%, p = 0.02). We observed a direct increase in mortality (and a reduction in closure rate) for each 6-h delay in surgery to source control.

Conclusion

Early source control using OA management significantly improves outcome of patients with severe IAIs. This damage control approach well fits to the treatment of time-related conditions, particularly in case of critically ill patients.

     

A critical appraisal of the quality of low back pain practice guidelines using the AGREE II tool and comparison with previous evaluations: a EuroAIM initiative

Purpose

To assess the methodologic quality of guidelines for the management of low back pain (LBP) and compare their recommendations.

Methods

No ethics committee approval was needed for this systematic review. In March 2017, a systematic search was performed using MEDLINE, EMBASE, National Guideline Clearinghouse, and National Institute for Health and Clinical Excellence to find practice guidelines of assessment and management of LBP. The evaluation of guidelines quality was performed independently by four authors using the AGREE II tool, and the results were compared with previous appraisals performed in 2004 and 2009.

Results

Of 114 retrieved guidelines, eight were appraised. All except one reached the level of “acceptable” in overall result, with two of them reaching the highest scores. Only two guidelines reached a level of “acceptable” in every domain; the others had at least one domain with low scores. The guidelines had the higher scores (range?=?63–94%) on “Scope and purpose” and “Clarity of presentation” (47–89%). “Stakeholder Involvement” has the highest variability between the guidelines results (40–96%). “Rigor of Development” reached an intermediate mean result (34–90%), “Applicability” (42–70%), and “Editorial Independence” (38–85%). Only three guidelines had a radiologist among authors and reached higher scores compared to guidelines without a radiologist among the authors. Compared to previous assessments, low-level guidelines were 53% in 2004, 36% in 2009, and 13% in 2017.

Conclusions

Considering all guidelines, only one had a “low” overall score, while half of them were rated as of “high” quality. Future guidelines might take this into account to improve clinical applicability.

Graphical abstract

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IgA nephropathy

Summary Seventy-five biopsy samples from patients with chronic renal disorders were examined by the usual techniques of light microscopy and immunofluorescence; in fifteen patients IgA nephropathy was found. These patients were young adults; the onset of the disease was characterized by macrohematuria, and recurrent episodes of hematuria were observed. Histological examination revealed proliferative endothelio-mesangial glomerulonephritis at various stages of development with focal or diffuse patterns; immunofluorescence revealed constant and intense positive reactions for IgA mainly in association with C3. It is assumed that there is a relationship connecting the more advanced histological changes, a more severe clinical course and the presence of IgM deposits.     

Influence of age and sex on five human plasma lysosomal enzymes assayed by automated procedures

Automated fluorimetric procedures for the assay of five lysosomal glycohydrolases—β-N-acetylglucosaminidase; β-galactosidase; β-glucuronidase; α-mannosidase; α-fucosidase—in human plasma were set up. A Carlo Erba autoanalyser CLA 1500, provided with a sampler refrigerating unit and connected with a recording Turner Mod 111 fluorimeter was employed. The automated procedures, under the established optimal conditions, proved to be highly accurate and reproducible.Using the automated assay procedures the effect of sex and age on the plasma levels of the same enzymes was studied. 1273 randomly selected healthy subjects were studied. No sex differences were observed for all the enzymes studied with the exception of β-glucuronidase which displayed higher values (about 30%) in males from 25 to 60 years. The developmental profiles of all enzymes in females and males were similar and characterised by: (a) absolute maximum level in the umbilical cord blood; (b) absolute minimum level at 10–14 years; (c) decrease to a second minimum occurring around 35 years (not displayed by β-galactosidase and by β-glucuronidase in males); (e) slow further increase up to the elderly level which was then maintained till the oldest age examined, 74 years.     

Bioadhesive film for the transdermal delivery of lidocaine: in vitro and in vivo behavior.

The aim of this work was to study, in vitro and in vivo, the behavior of a skin bioadhesive film containing lidocaine. The film characterization included drug transport studies through skin in vitro and in vivo tape stripping with and without iontophoresis. We studied the effect of drug loading in order to identify the release mechanism. Finally, the release rate was compared with a lidocaine commercial gel, to assess the therapeutic value. From the data obtained it can be concluded that the monolayer film acts as a water-permeable transdermal/dermal patch on application to the skin. The permeation kinetics across the skin was not linear, but the patch acted as a matrix controlling drug delivery. Additionally, the permeation rate increased with drug loading. The in vivo experiments with tape stripping indicated that the presence of water during film application is essential to achieve not only the proper adhesion but also an effective accumulation. The application of electric current to the patch can further increase the amount of drug accumulated in the stratum corneum.