Diabetes mellitus, left ventricular dysfunction and congestive heart failure]

Diabetes is a well known risk factor for the development of congestive heart failure. Epidemiological evidence in the community underscores the prevalence of left ventricular systolic dysfunction in diabetic patients as 2-fold with respect to non-diabetic ones, with half of them completely asymptomatic. Diastolic dysfunction in diabetic hearts, in comparison with non-diabetic, is even more frequent. The high prevalence has been explained by the frequent coexistence of an underlying diabetic cardiomyopathy, hypertension and ischemic heart disease. In these patients, the diabetic metabolic derangement, together with the early activation of sympathetic nervous system, induce a decrease of myocardial function. The activation of renin-angiotensin system results in an unfavorable cardiac remodeling. The progression from myocardial damage to overt dysfunction and heart failure is often asymptomatic for a long time and frequently undiagnosed and untreated. Currently, the widespread availability of echocardiography and possibly the use of cardiac natriuretic peptides, may allow for an earlier recognition of most of such patients. In heart failure, diabetic patients have a worse prognosis than non-diabetics. The available pharmacological treatments, such as ACE-inhibitors, beta-blockers and possibly angiotensin receptor blockers, togheter with a tight glycemic control, may be effective to reverse the remodeling process and prevent cardiovascular events. In order to identify most of the diabetic patients at risk of development of left ventricular dysfunction and to prevent its progression to overt heart failure, it seems important to elaborate a screening strategy in order to diagnose and treat most of diabetic patients with myocardial damage.     

Iron acquisition from heme and hemoglobin by a Serratia marcescens extracellular protein.

Several pathogenic bacteria are able to use heme and hemoproteins as iron sources independent of siderophore production by mechanisms involving outer membrane heme-binding proteins and heme transport systems. Here we show that Serratia marcescens has such a property and we identify an extracellular heme-binding protein, HasA (for heme acquisition system), allowing the release of heme from hemoglobin. This protein is secreted by S. marcescens under conditions of iron depletion and is essential for heme acquisition.     

Effectiveness of combined therapy with angiotensin-converting enzyme inhibitors and statins in reducing mortality in diabetic patients with critical limb ischemia: An observational study

Aims

To investigate the effect of combined treatment with angiotensin-converting enzyme inhibitors (ACE) and statins on mortality in diabetic patients with critical limb ischemia (CLI).

Methods

Prospective observational study of 553 consecutive diabetic patients admitted because of CLI followed for a mean of 2.2 years. All patients underwent peripheral revascularization and antithrombotic therapy was prescribed or continued and therapy with statin and ACE was recorded. Mortality from any cause was assessed and Kaplan–Meier analyses were performed to compare the relationship between survival and recorded variables.

Results

One hundred thirty-nine patients did not have therapy with statin or an ACE, 78 had therapy with statin without ACE, 164 had therapy with ACE without statin and 172 patients had therapy with both statin and ACE. One hundred thirty-six patients died, 45/139 with neither statin nor ACE, 40/164 with ACE only, 26/78 with statin only, and 25/172 with both statin and ACE. Multivariate analysis confirmed the independent role of age, history of stroke, renal insufficiency and dialysis. Combined treatment with ACE and statin appeared to have a protective role.

Conclusions

In patients with diabetes and CLI mortality after two years is high. Life expectancy was better in patients receiving combined therapy with ACE and statin but not with therapy with only a statin or an ACE.     

Predicting severity of pathological scarring due to burn injuries: a clinical decision making tool using Bayesian networks

It is important for clinicians to understand which are the clinical signs, the patient characteristics and the procedures that are related with the occurrence of hypertrophic burn scars in order to carry out a possible prognostic assessment. Providing clinicians with an easy‐to‐ use tool for predicting the risk of pathological scars. A total of 703 patients with 2440 anatomical burn sites who were admitted to the Department of Plastic and Reconstructive Surgery, Burn Center of the Traumatological Hospital in Torino between January 1994 and May 2006 were included in the analysis. A Bayesian network (BN) model was implemented. The probability of developing a hypertrophic scar was evaluated on a number of scenarios. The error rate of the BN model was assessed internally and it was equal to 24·83%. While classical statistical method as logistic models can infer only which variables are related to the final outcome, the BN approach displays a set of relationships between the final outcome (scar type) and the explanatory covariates (patient's age and gender, burn surface area, full‐thickness burn surface area, burn anatomical area and wound‐healing time; burn treatment options such as advanced dressings, type of surgical approach, number of surgical procedures, type of skin graft, excision and coverage timing). A web‐based interface to handle the BN model was developed on the website www.pubchild.org (burns header). Clinicians who registered at the website could submit their data in order to get from the BN model the predicted probability of observing a pathological scar type.     

Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line

It is known that the density of peripheral benzodiazepine receptors (PBR) increases after brain damage. Astrocytes are among the cell types where PBR ligand binding has been detected and may be involved in the response to neuronal injury and regeneration. Consistent with the hypothesis, the apparent density of PBR sites in astrocytes is increased by both cytokines and neurotoxins. However, microglia, the resident macrophages which represent 5–15% of glial cell populations have not been evaluated for the presence of the PBR. In the present study, we report the presence of [³H]Ro5-4864 binding in microglial cells. In particular, we used BV-2 cells, an immortalized cell line of murine microglial cells. High affinity binding of [³H]Ro5-4864 to a single site was detected in membranes prepared from BV-2 cells (K_D = 4.4 nM, B_max = 3,800 fmoles/mg protein). Various ligands for the PBR displaced [³H]Ro5-4864 binding with the following rank order of potencies: PK11195 = Ro5-4864 > FGIN-1-27 > triazolam = diazepam > beta-pro-pyl-beta-carboline-3-carboxylate = clonazepam > lorazepam = flurazepam >> chlordiazepoxide = clorazepate. Subcellular fractionationstudies indicate that the majority of the Ro5-4864 binding sites is in the mitochondrial fraction. The remainder is found in non-mitochondrial cell fractions. The [³H]Ro5-4864 binding observed on intact cells had characteristics similar to those found on membranes. The presence of a high density of PBRs in these cells establish the basis for additional investigations into their possible functional role, if any, in the microglial response to neuronal injury. © 1996 Wiley-Liss, Inc.     

Modelling and Performance Analysis of MgB2 and Hybrid Magnetic Shields

Superconductors are strategic materials for the fabrication of magnetic shields, and within this class, MgB2 has been proven to be a very promising option. However, a successful approach to produce devices with high shielding ability also requires the availability of suitable simulation tools guiding the optimization process. In this paper, we report on a 3D numerical model based on a vector potential (A)-formulation, exploited to investigate the properties of superconducting (SC) shielding structures with cylindrical symmetry and an aspect ratio of height to diameter approaching one. To this aim, we first explored the viability of this model by solving a benchmark problem and comparing the computation outputs with those obtained with the most used approach based on the H-formulation. This comparison evidenced the full agreement of the computation outcomes as well as the much better performance of the model based on the A-formulation in terms of computation time. Relying on this result, the latter model was exploited to predict the shielding properties of open and single capped MgB2 tubes with and without the superimposition of a ferromagnetic (FM) shield. This investigation highlighted that the addition of the FM shell is very efficient in increasing the shielding factors of the SC screen when the applied magnetic field is tilted with respect to the shield axis. This effect is already significant at low tilt angles and allows compensating the strong decrease in the shielding ability that affects the short tubular SC screens when the external field is applied out of their axis.     

The 17-year single-center experience with the use of azathioprine to maintain remission in ulcerative colitis

Despite the accumulation of positive data, the role of azathioprine (AZA) in the maintenance of remission of ulcerative colitis is still controversial. We looked at the follow-up of the ulcerative colitis patients who, after responding to either steroids or cyclosporin (CsA), received AZA at our referral center for over a decade. The 39 patients (29 m/10f) were treated between 1991 and 2007. Twenty-five of them had responded to CsA, the remaining 14 to corticosteroids. AZA was usually overlapped with either of the two agents at the initial dose of 2 mg/kg/day. The definitions of remission, relapse, and AZA toxicity followed commonly agreed criteria. The median duration of the AZA treatment was 14 months (<1–201). Fifty-two percent and 14%, respectively, of the CsA and the steroid responders needed surgery (overall rate = 38%). The figures were 32 and 15 at the first year. The majority of the patients had 1–2 relapses often in connection with withdrawal of AZA; only 3 of these relapsers needed hospitalization. AZA caused toxicity in 16/39 (41%) patients, requiring withdrawal in 23% of the cases; leukopenia (17%) and hepatitis/cholestasis (10%) ranked first and second for frequency. All of the patients in whom AZA was stopped (or reduced) relapsed. In conclusion, the 1-year colectomy rates compare favorably with the figures reported by the literature. By contrast, the toxicity rates were higher than expected. Failure to genotype or to use escalating AZA doses can only be hypothesized as causes.     

Accelerated rehabilitation after arthroscopic meniscal repair: A clinical and magnetic resonance imaging evaluation

Twenty-two patients who underwent meniscal repair using the outside-in technique combined with anterior cruciate ligament (ACL) reconstruction were submitted to an accelerated rehabilitation protocol that included immediate full range of motion and weightbearing. The patients were reviewed postoperatively by means of clinical assessment and magnetic resonance imaging (MRI) after an average of 28 months. Clinical evaluation was performed according to the International Knee Documentation Committee form, and sagittal knee laxity was measured with a KT-2000 arthrometer (MedMetric Corp, San Diego, CA). The MRI scans were obtained using a 0.2-T high-resolution MRI unit dedicated to the study of limbs, and the meniscal signal was graded according to a modified Crues classification. Overall, 77.3% of patients reported clinically good results. Loss of extension of <5° was detected in only 2 patients (9.1%). Three out of 22 patients showed clinical signs of meniscal retear. One of these patients had a second operation for a bucket-handle tear. The presence of a full-thickness rim at MRI evaluation, present in 10 patients (45.5%), did not correlate with the presence of clinical symptoms of retear. Instead, the 3 symptomatic patients presented a complete rim with a gap>1 mm between the meniscal wall and the fragment of the posterior horn. This finding is believed to be a more reliable indicator for retear following meniscal repair. The low failure rate in this series suggests that an aggressive rehabilitation regimen may be prescribed without deleterious effects in subjects undergoing ACL reconstruction and concomitant meniscus repair.     

Efficacy of Teduglutide for Parenteral Support Reduction in Patients with Short Bowel Syndrome: A Systematic Review and Meta-Analysis

Teduglutide has been described as an effective treatment for parenteral support (PS) reduction in patients with short bowel syndrome (SBS). However, a quantitative summary of the available evidence is still lacking. PubMed/Medline, EMBASE, Cochrane library, OVID, and CINAHL databases were systematically searched up to July 2021 for studies reporting the rate of response (defined as a ≥20% reduction in PS) to teduglutide among PS-dependent adult patients. The rate of weaning (defined as the achievement of PS independence) was also evaluated as a secondary end-point. Ten studies were finally considered in the meta-analysis. Pooled data show a response rate of 64% at 6 months, 77% at 1 year and, 82% at ≥2 years; on the other hand, the weaning rate could be estimated as 11% at 6 months, 17% at 1 year, and 21% at ≥2 years. The presence of colon in continuity reduced the response rate (−17%, 95%CI: (−31%, −3%)), but was associated with a higher weaning rate (+16%, 95%CI: (+6%, +25%)). SBS etiology, on the contrary, was not found to be a significant predictor of these outcomes, although a nonsignificant trend towards both higher response rates (+9%, 95%CI: (−8%, +27%)) and higher weaning rates (+7%, 95%CI: (−14%, +28%)) could be observed in patients with Crohn’s disease. This was the first meta-analysis that specifically assessed the efficacy of teduglutide in adult patients with SBS. Our results provide pooled estimates of response and weaning rates over time and identify intestinal anatomy as a significant predictor of these outcomes.