Natriuretic peptide testing in primary care patients

The evaluation of cardiac endocrine function by means of automated robust assays has permitted the introduction of a cheap and powerful clinical tool. Plasma concentration of B-type-related natriuretic peptides is a marker of either hemodynamic or neurohormonal stress on the heart and has been validated within the diagnostic and prognostic domain in patients with suspected or ascertained heart failure, mostly in the in-hospital setting. Evidence is growing, supporting an out-of-hospital use, namely in primary care. Its implementation in this setting in screening programs and diagnostic algorithms might contribute to decrease the apparent disparity between the general practitioner and the specialist approach to disease management.     

Aeromonas veronii biovar veronii and sepsis-infrequent complication of biliary drainage placement: A case report

BACKGROUND Aeromonas species are uncommon pathogens in biliary sepsis and cause substantial mortality in patients with impaired hepatobiliary function. Asia has the highest incidence of infection from Aeromonas,whereas cases in the west are rare.CASE SUMMARY We report the case of a 64-year-old woman with advanced pancreatic cancer and jaundice who manifested fever,abdominal pain,severe thrombocytopenia,anemia and kidney failure following the insertion of a percutaneous transhepatic biliary drainage. Blood culture results revealed the presence of Aeromonas veronii biovar veronii(A. veronii biovar veronii). After antibiotic therapy and transfusions,the life-threatening clinical conditions of the patient improved and she was discharged.CONCLUSION This was a rare case of infection,probably the first to be reported in West countries,caused by A. veronii biovar veronii following biliary drainage. A finding of Aeromonas must alert clinician to the possibility of severe sepsis.     

Complementary therapy and support services for formal and informal caregivers in Italian palliative care hospices: an exploratory and descriptive study

Purpose  

The present study is aimed to assess the availability and use of complementary medicine (CM) therapies in Italian palliative care hospices, and the support services available to caregivers and hospice staff.     

Myocardial Salvage Imaging: Where Are We and Where Are We Heading? A Cardiac Magnetic Resonance Perspective

Purpose of Review

Cardiac magnetic resonance (CMR) has emerged in recent years as a reliable tool to assess, in a single examination after a reperfused myocardial infarction, the initially area at risk (AAR), the final infarct size (IS), and from their difference the salvaged myocardium (SM). The aim of the present review is to summarize recent advances in the CMR imaging of SM.

Recent Findings

While there is consensus on the use of late gadolinium enhancement (LGE) to calculate IS, how to assess the AAR is a debated topic. The use of T2-weighted short-TI inversion recovery (T2W-STIR) is to date supported by a large amount of data, but it is affected by several limitations. Newer techniques have been developed to overcome T2W-STIR limitations, some of them have been already used in randomized clinical trials (RCTs) while others are showing promising results. The use of CMR to generate surrogate endpoints in RCTs is gaining attention; in this context, analysis of data from recent RCTs suggests that the assessment of SM as outcome measure could be useful to reduce sample sizes and costs of trials.

Summary

CMR is a reliable technique for the assessment of SM. LGE is the gold standard for IS measurement, while which is the best technique for the evaluation of AAR is still debated. When using CMR-derived endpoints in RCTs, the assessment of SM is advisable.

     

Postural Rehabilitation and Kinesio Taping for Axial Postural Disorders in Parkinson's Disease

Objective

To assess the effects of postural rehabilitation (PR) on trunk asymmetry and balance, with and without Kinesio taping (KT) of the back muscles as additional treatment, in patients with Parkinson's disease (PD) who have postural disorders.

Design

Single-blind, randomized controlled trial with 1-month follow-up.

Setting

Ambulatory care in referral center.

Participants

Patients (N=20) with PD showing postural abnormalities of the trunk, in the sagittal and/or coronal plane.

Interventions

Four weeks of patient-tailored proprioceptive and tactile stimulation, combined with stretching and postural reeducation, was provided to 13 subjects (PR group), while 7 received no treatment (control group). Six of the 13 subjects receiving PR also had KT strips applied to their trunk muscles, according to the features of their postural abnormalities.

Main Outcome Measures

Berg Balance Scale, Timed Up and Go, and degrees of trunk bending in the sagittal and coronal planes were assessed at the enrollment (t0), 1 month later (t1), and 2 months later (t2).

Results

At t1, all treated patients showed a significant improvement in trunk posture in both the sagittal (P=.002) and coronal planes (P=.01), compared with baseline. Moreover, they showed an improvement in measures of gait and balance (P<.01). Benefits persisted at t2 for all measures, except lateral trunk bend. No differences were found when comparing the PR and KT groups.

Conclusions

The combination of active posture correction and trunk movements, muscle stretching, and proprioceptive stimulation may usefully impact PD axial symptoms. Repeated training is advocated to avoid waning of the effect.     

Characterization of the Population Pharmacokinetics of Ampicillin in Neonates Using an Opportunistic Study Design

Although ampicillin is the most commonly used drug in neonates, developmental pharmacokinetic (PK) data to guide dosing are lacking. Ampicillin is primarily renally eliminated, and developmental changes are expected to influence PK. We conducted an open-label, multicenter, opportunistic, prospective PK study of ampicillin in neonates stratified by gestational age (GA) (≤34 or >34 weeks) and postnatal age (PNA) (≤7 or >7 days). Drug concentrations were measured by tandem mass spectrometry. PK data were analyzed using population nonlinear mixed-effects modeling in NONMEM 7.2. Monte Carlo simulations were conducted to determine the probability of target attainment for the time in which the total steady-state ampicillin concentrations remained above the MIC (T>MIC) for 50%, 75%, and 100% of the dosing interval. A total of 142 PK samples from 73 neonates were analyzed (median [range] GA, 36 [24 to 41] weeks; PNA, 5 [0 to 25] days). The median ampicillin dose was 200 (100 to 350) mg/kg/day. Postmenstrual age and serum creatinine were covariates for ampicillin clearance (CL). A simplified dosing regimen of 50 mg/kg every 12 h for GA of ≤34 weeks and PNA of ≤7 days, 75 mg/kg every 12 h for GA of ≤34 weeks and PNA of ≥8 and ≤28 days, and 50 mg/kg every 8 h for GA of >34 weeks and PNA of ≤28 days achieved the prespecified surrogate efficacy target in 90% of simulated subjects. Ampicillin CL was associated with neonatal development. A simplified dosing regimen stratified by GA and PNA achieves the desired surrogate therapeutic target in the vast majority of neonates.     

A novel self-lipid antigen targets human T cells against CD1c+ leukemias

T cells that recognize self-lipids presented by CD1c are frequent in the peripheral blood of healthy individuals and kill transformed hematopoietic cells, but little is known about their antigen specificity and potential antileukemia effects. We report that CD1c self-reactive T cells recognize a novel class of self-lipids, identified as methyl-lysophosphatidic acids (mLPAs), which are accumulated in leukemia cells. Primary acute myeloid and B cell acute leukemia blasts express CD1 molecules. mLPA-specific T cells efficiently kill CD1c⁺ acute leukemia cells, poorly recognize nontransformed CD1c-expressing cells, and protect immunodeficient mice against CD1c⁺ human leukemia cells. The identification of immunogenic self-lipid antigens accumulated in leukemia cells and the observed leukemia control by lipid-specific T cells in vivo provide a new conceptual framework for leukemia immune surveillance and possible immunotherapy.CD1-restricted T lymphocytes recognize lipid antigens presented by the nonpolymorphic, MHC class I–related family of CD1 molecules (Porcelli and Modlin, 1999). CD1-restricted T cells can respond to lipid antigens derived from microbial cells and may exert protective roles during host infection (Moody et al., 2000, 2004; Amprey et al., 2004; Gilleron et al., 2004; Kinjo et al., 2005; Sriram et al., 2005; Wu et al., 2005; Montamat-Sicotte et al., 2011). A striking characteristic of many CD1-restricted T cells is autoreactivity against different types of APCs even in the absence of microbial antigens, implying that they can also recognize endogenous self-lipid molecules (Dellabona et al., 1993; Mattner et al., 2005; Vincent et al., 2005). Autoreactive T cells recognize different types of self-lipids present in cell membranes and synthesized within different cellular compartments (Shamshiev et al., 1999, 2000; Gumperz et al., 2000; Wu et al., 2003; De Libero et al., 2005). CD1a- and CD1c-autoreactive T cells are relatively abundant among circulating T cells in healthy individuals (de Jong et al., 2010; de Lalla et al., 2011) and might become activated by host antigens in autoimmune diseases and cancer. Lipid-specific T cells can control cancer cell growth in mouse models (Berzofsky and Terabe, 2009) as well as in human patients (Dhodapkar and Richter, 2011; Metelitsa, 2011), but it remains unknown whether they recognize unique lipids expressed by tumor cells.Acute leukemia comprises a heterogeneous group of hematological disorders characterized by blood and bone marrow accumulation of immature and abnormal cells derived from hematopoietic precursors (Pui et al., 2004; Rubnitz et al., 2008). Current therapy for acute leukemia is based on polychemotherapy and allogeneic hematopoietic stem cell (HSC) transplantation (HSCT). A major cause of treatment failure and area of substantial unmet need in HSCT is posttransplant regrowth of residual leukemia blasts that survive the conditioning regimen (Wingard et al., 2011). Donor-derived T cells transferred into patients may induce a beneficial graft versus leukemia (GVL) reaction capable of maintaining remission (Kolb, 2008), but grafted T cells are also capable of killing patient cells in nonhematopoietic tissues to induce detrimental graft versus host disease (GVHD; Socié and Blazar, 2009). A promising therapeutic strategy is the selective targeting of T cell responses against malignant hematopoietic cells, while maintaining hematopoietic capacity among grafted cells and preserving organ functions in recipient patients (Kolb, 2008). Because CD1 molecules are both nonpolymorphic and preferentially expressed by mature hematopoietic cells (Porcelli and Modlin, 1999; Brigl and Brenner, 2004), targeting tumor-associated lipid antigens presented by CD1 molecules might provide opportunities to improve the efficacy of HSCT. Immune recognition of tumor-associated lipid antigens may also complement ongoing antitumor responses mediated by protein antigens.Here we have identified the novel self-lipid antigen that stimulates CD1c autoreactive T cells to destroy tumor cell lines and primary human leukemia cells. We report that both group 1 CD1 molecules and a novel class of tumor-associated lipids are broadly expressed by different types of acute leukemia. In addition to killing CD1c⁺ leukemia cell lines and primary blasts in vitro, the CD1c-restricted T cells also displayed therapeutic efficacy in a mouse xenograft model of human leukemia. Our findings provide proof-of-concept evidence that T cell responses against lipids accumulated in acute leukemia could be exploited for leukemia immunotherapy.