Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE)

The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.     

The effects of anti-angiogenic therapy on the formation of radiation-induced microbleeds in normal brain tissue of patients with glioma

Background

Radiotherapy (RT) is an integral component in managing patients with glioma, but the damage it may cause to healthy brain tissue and quality of life is of concern. Susceptibility-weighted imaging (SWI) is highly sensitive to the detection of microbleeds that occur years after RT. This study''s goals were to characterize the evolution of radiation-induced microbleeds in normal-appearing brain and determine whether the administration of an anti-angiogenic agent altered this process.

Methods

Serial high-resolution SWI was acquired on 17 patients with high-grade glioma between 8 months and 4.5 years posttreatment with RT and adjuvant chemotherapy. Nine of these patients were also treated with the anti-angiogenic agent enzastaurin. Microbleeds were identified as discrete foci of susceptibility not corresponding to vessels, tumor, or postoperative infarct, and counted in normal-appearing brain. Analysis of covariance was performed to compare slopes of regression of individual patients'' microbleed counts over time, Wilcoxon rank-sum tests examined significant differences in rates of microbleed formation between groups, and linear and quadratic mixed-effects models were employed.

Results

The number of microbleeds increased with time for all patients, with initial onset occurring at 8–22 months. No microbleeds disappeared once formed. The average rate of microbleed formation significantly increased after 2 years post-RT (P < .001). Patients receiving anti-angiogenic therapy exhibited fewer microbleeds overall (P < .05) and a significant reduction in initial rate of microbleed appearance (P = .01).

Conclusions

We have demonstrated a dramatic increase in microbleed formation after 2 years post-RT that was decelerated by the concomitant administration of anti-angiogenic therapy, which may aid in determining brain regions susceptible to RT.     

Hyperhomocysteinaemia in black patients with cerebral thrombosis

Hyperhomocysteinemia is regarded as a risk factor for stroke but its pathogenetic role has not yet been established in Black patients. We studied 24 Black patients admitted with cerebral thrombosis, and compared them with age- and sex-matched apparently healthy controls from the same community. Total homocysteine (tHcy) (free homocysteine, protein-bound homocysteine, the disulfide homocystine and the mixed disulfide homocysteine-cysteine) concentration was 10.91 (4.95-23.05) mumol/l in the stroke patients and 8.73 (3.95-15.10) mumol/l in controls (p = 0.031). This difference could not be explained by differences in vitamin B12, vitamin B6 or folate status. A subgroup of nine stroke patients with hypercreatininaemia (> 90 mumol/l, 75% of control concentrations) had significantly higher plasma tHcy concentrations [median (range) 9.10 (5.40-15.10) mumol/l] compared with controls [8.65 (3.96-13.89) mumol/l] (p = 0.002). Plasma tHcy concentrations of stroke patients with normal serum creatinine concentrations were not significantly different to those of controls. Hyperhomocysteinemia in Black patients with stroke may be partially caused by renal insufficiency. Therefore, while hyperhomocysteinemia may increase the risk of stroke, it is unlikely to be a primary initiating factor.      

The relative roles of major and minor histocompatibility antigens in the induction of immunologic unresponsiveness by blood transfusion

Renal allograft survival may be prolonged indefinitely in some strains of rats following preoperative transfusion with whole blood from the organ donor. Similarly donor-specific transfusion results in a reduction in the proliferative response of lymph node (LN) white cells (WBCs) to donor-specific stimulators in mixed-lymphocyte culture (MLC). To determine the relative roles of major and minor histocompatibility antigens in the depression of the proliferative response, in vitro lymphocyte proliferation assays were performed using congenic rat strains as blood donors. Unidirectional MLCs were set up between haplotype-disparate responder and stimulator LN cells, in cases in which the responding cells had been harvested from rats transfused with blood that shared either some, all, or none of the major histocompatibility complex genes with the stimulator strain. The proliferative response of LN cells harvested from rats transfused with blood sharing major (class I or II) or minor antigens, or both, with the in vitro stimulator cells was significantly less than the response of cells harvested from nontransfused controls. No single-locus product was more or less effective than whole blood in depressing cell proliferation. These data suggest that the beneficial effect of preoperative random blood transfusions observed in clinical transplantation may arise from the fortuitous sharing by the blood donor and the subsequent organ donor of not only a single major histocompatibility antigen but also of minor histocompatibility antigens.     

Clinical and Histological Spectrum of Osteomalacia Among Asians in South London

In a prospective study of 175 adult Asian patients attendinga medical out-patient clinic we found a spectrum of metabolicbone disease. Twenty-four patients (13.5 per cent) had definiteosteomalacia, of whom 11 (6 per cent) had severe clinical osteomalaciaon the basis of associated symptoms and radiological signs.Fifteen (8.5 per cent) had borderline osteomalacia, while theremaining 136 (78 per cent) had normal bone biopsy, or werepresumed to be normal. This histological spectrum was paralleled by the increasingprevalence of musculoskeletal symptoms (thi gh pain, changein gait and difficulty rising from seated position) attributableto osteomalacia. Multivariate analysis showed that the majordeterminant of osteomalacia in Asians in South London was vegetariandiet. Increasing severity of bone disease was associated withincreasingly strict vegetarian practice, which accounted forthe excess risk of females, Hindus, and Asians originating fromEast Africa. Covering skin when outdoors also contributed tothe female excess risk, and suggested a role for reduced solarexposure. Clinically significant osteomalacia is underdiagnosed in theAsian population, but evidence of dietary adaptation suggeststhis problem may diminish with time.     

Influence of haemodialysis on high-sensitivity C-reactive protein, lipoprotein(a), apolipoproteins A and B

OBJECTIVES: There is debate on the influence of haemodialysis (HD) on lipoprotein(a). DESIGN AND METHODS: Lp(a), apo A, apo B and high-sensitivity C-reactive protein (hs-CRP) were measured in 46 patients pre- and post-HD. RESULTS: The median Lp(a) concentration significantly decreased post-HD (106 vs. 145 mg/L, p<0.001). No significant variations were observed for apo A, apo B and hs-CRP. Comparable results were observed with high- and low-flux membranes. CONCLUSION: HD is effective in lowering Lp(a).     

Hematologic effects of flt3 ligand in vivo in mice

We have investigated the effects of in vivo treatment with flt3 ligand (FL) on murine hematopoiesis, including mobilization of progenitors into the peripheral blood (PB). Mice were injected once daily with 10 micrograms recombinant human FL for 15 days. On days 3, 5, 8, 10, 15, and 22, mice were killed and analyzed for the number of leukocytes and colony-forming units (CFU) in bone marrow (BM), spleen, and PB. Splenic and PB cellularity increased with time in FL-treated mice. In the spleen, there was an increase in B cells, myeloid cells, and nucleated erythroid cells; in the PB, there was an increase in lymphocytes, granulocytes, and monocytic cells. The maximal number of CFU in the BM was observed after 3 days of FL treatment, giving 3.7- and 7.3-fold increases in CFU-granulocyte-macrophage (CFU-GM) and CFU-granulocyte, erythrocyte, monocyte, megakaryocyte (CFU-GEMM), respectively, compared with mouse serum albumin (MSA)-treated controls. After 8 days of FL treatment, there was a maximal 123- and 108-fold increase in splenic CFU-GM and CFU-GEMM, respectively. The maximal number CFU-GM and CFU- GEMM were seen in PB on day 10, with 537- and 585-fold increases, respectively. Burst-forming units-erythroid (BFU-E) increased in the same time frame as those of CFU-GM and CFU-GEMM in BM, spleen, and PB, although the magnitude was not as great. Primitive day-13 CFU-spleen (CFU-S) and phenotypically defined stem cells were also mobilized into the PB of FL-treated mice with similar kinetics and magnitude to that of CFU-GM and CFU-GEMM. We conclude from these studies that FL, when administered as a single agent, is a potent mobilizer of hematopoietic progenitors into the PB.     

Cosmeceutical peptides

ABSTRACT:  Peptide cosmeceuticals are one of the new, popular options to treat aging skin. There are three main categories of cosmeceutical peptides: signal peptides, neurotransmitter-affecting peptides and carrier peptides. Although their benefits currently may not be as rigorously tested as most FDA-regulated drugs, the evidence to support their use is growing. This article attempts to review the various current popular cosmeceutical peptides, the published studies on their theoretical effects, and their practical use in dermatology.     

18F‐fluoro‐2‐deoxy‐D‐glucose positron emission tomography and positron emission tomography/computed tomography imaging of malignant pleural mesothelioma*

Malignant pleural mesothelioma (MPM) is the most common primary pleural tumor and its incidence is rising. Its diagnosis, staging and response assessment are challenging for imaging. Integrated positron emission tomography (PET)/CT increases the accuracy of overall staging in patients with mesothelioma and improves the selection of patients for curative surgical resection. It is particularly useful in identifying occult distant metastases. It may be used to predict prognosis and to assess the metabolic response to therapy.