Predictors of Mortality in Bloodstream Infections Caused by Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae: Importance of Combination Therapy

Background.?The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens is a major challenge for clinicians. Methods.?In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality. Results.?The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P?=?.02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio [OR]: 7.17; 95% confidence interval [CI]: 1.65-31.03; P?=?.008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61-10.76; P?=?.003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02-1.07; P?相似文献   

Effects of Opiates and HIV Proteins on Neurons: The Role of Ferritin Heavy Chain and a Potential for Synergism

Human immunodeficiency virus 1 (HIV-1) and its associated proteins can have a profound impact on the central nervous system. Co-morbid abuse of opiates, such as morphine and heroin, is often associated with rapid disease progression and greater neurological dysfunction. The mechanisms by which HIV proteins and opiates cause neuronal damage on their own and together are unclear. The emergence of ferritin heavy chain (FHC) as a negative regulator of the chemokine receptor CXCR4, a co-receptor for HIV, may prove to be important in elucidating the interaction between HIV proteins and opiates. This review summarizes our current knowledge of central nervous system damage inflicted by HIV and opiates, as well as the regulation of CXCR4 by opiate-induced changes in FHC protein levels. We propose that HIV proteins and opiates exhibit an additive or synergistic effect on FHC/CXCR4, thereby decreasing neuronal signaling and function.     

Periocular Cutaneous Anaplastic Large Cell Lymphoma Clearance with Brentuximab Vedotin

The treatment options for primary cutaneous anaplastic large cell lymphoma are numerous, including excision, external beam radiation, methotrexate, and chemotherapy. In patients with recalcitrant tumors, alternative options may be necessary. The authors report a 60-year-old man with a 6cm primary cutaneous anaplastic large cell lymphoma located on the right cheek, near the eye. After failing four months of methotrexate, and due to concern for ocular radiation toxicity, the patient started brentuximab vedotin, an anti-CD30 antibody-drug conjugate. With two cycles of brentuximab vedotin, he had a complete response that was histologically confirmed. Six months after a total of four cycles, he remains clear. He experienced no side effects other than a mild infusion reaction. Brentuximab vedotin may be an effective option for primary cutaneous anaplastic large cell lymphoma in patients with large tumors in cosmetically sensitive areas, those who have not responded to conventional therapy, or those who have contraindications to radiation therapy. Optimal dosing for primary cutaneous anaplastic large cell lymphoma and long-term outcomes are not currently known.Primary cutaneous anaplastic large cell lymphomaa (pcALCL) is a subtype of cutaneous T-cell lymphoma (CTCL) histologically characterized by large, highly typical CD30+ T-cells that clinically presents as a solitary tumor. The authors report a case of a large pcALCL arising on the face with periorbital extension. The size and periorbital location were relative contraindications to radiation therapy and surgery. Oral weekly methotrexate was initiated, but the tumor enlarged in size and the growth extended near the eye despite generally adequate doses. After brief treatment with brentuximab vedotin, the tumor resolved completely.     

Left ventricular geometry correlates with early repolarization pattern in adolescent athletes

Some forms of early ECG repolarization QRS pattern (ERp) with J‐point elevation of 0.1 mV in two contiguous inferior and/or lateral leads with or without ST‐elevation are potentially associated with a higher arrhythmic risk in adults. We assessed the prevalence of ERp among non‐professional adolescent athletes and correlated it with age, sex, ethnicity, and structural and electric cardiac parameters. We retrospectively analyzed 414 ECGs obtained from young athletes referred to our center from 2006 to 2017. We found ERp in 22% of cases. In the ERp group, we found a greater percentage of black athletes, a higher systolic blood pressure, and lower heart rate (HR) compared with the group without ERp. This pattern was less frequent in female athletes. In athletes with ERp, the occurrence of ventricular ectopic beats was less frequent and QRS‐duration was shorter. They also exhibited greater (a) ECG‐based left ventricular hypertrophy (LVH), (b) left ventricular mass, and (c) relative wall thickness (RWT), suggesting a tendency to concentric geometry. At logistic regression analysis, we found that HR (OR 0.98 [0.96‐0.99] P = .013), QRS‐duration (OR 0.96 [0.94‐0.99], P = .003), LVH (OR 1.09 [1.05‐1.12], P < .001), and RWT (OR 1.08 [1.01‐1.16] P = .032) were significant predictors of ERp incidence. ERp is quite common in adolescent athletes and correlates with concentric LV remodeling. Specific clinical and ECG‐findings related to training such as lower HR, LVH, and QRS‐duration are also predictors of ERp. In adolescent non‐professional athletes, ERp is a benign finding associated with some structural and electric cardiac modifications induced by training.     

Ultrastructural characteristics of human mesenchymal stromal (stem) cells derived from bone marrow and term placenta

Human mesenchymal stromal (stem) cells (hMSCs) isolated from adult bone marrow (BM-hMSCs) as well as amnion (AM-hMSCs) and chorion (CM-hMSCs) term placenta leaves were studied by transmission electron microscopy (TEM) to investigate their ultrastructural basic phenotype. At flow cytometry, the isolated cells showed a homogeneous expression of markers commonly used to identify hMSCs, i.e., CD105, CD44, CD90, CD166, HLA-ABC positivities, and CD45, AC133, and HLA-DR negativities. However, TEM revealed subtle yet significant differences. BM-hMSCs had mesenchymal features with dilated cisternae of rough endoplasmic reticulum (rER) and peripheral collections of multiloculated clear blisters; this latter finding mostly representing complex foldings of the plasma membrane could be revelatory of the in situ cell arrangement in the niche microenvironment. Unlike BM-hMSCs, CM-hMSCs were more primitive and metabolically quiescent, their major features being the presence of rER stacks and large peripheral collections of unbound glycogen. AM-hMSCs showed a hybrid epithelial-mesenchymal ultrastructural phenotype; epithelial characters included non-intestinal-type surface microvilli, intracytoplasmic lumina lined with microvilli, and intercellular junctions; mesenchymal features included rER profiles, lipid droplets, and well-developed foci of contractile filaments with dense bodies. These features are consistent with the view that AM-hMSCs have a pluripotent potential. In conclusion, this study documents that ultrastructural differences exist among phenotypically similar hMSCs derived from human bone marrow and term placenta leaves; such differences could be revelatory of the hMSCs in vitro differentiation potential and may provide useful clues to attempt their in situ identification.     

Differences in the rate of carbapenem-resistant Enterobacteriaceae colonisation or Clostridium difficile infection following frontline treatment with tigecycline vs. meropenem for intra-abdominal infections

Objectives

We hypothesised that treatment with a tigecycline-based antimicrobial regimen for intra–abdominal infection (IAI) could be associated with lower rates of subsequent carbapenem-resistant Enterobacteriaceae (CRE) colonisation or Clostridium difficile infection (CDI) compared with a meropenem-based regimen.

A safety evaluation of budesonide MMX for the treatment of ulcerative colitis

Introduction: Budesonide belongs to low-bioavailability steroids class. A novel oral formulation of budesonide, which uses the Multi-Matrix System (MMX) for delivering drugs to the colon, is now available as a possible treatment of ulcerative colitis patients intolerant or not-responding to first-line therapy with 5-ASA.

Areas covered: in this review we present information about the development and the use of budesonide MMX and we provide data about its mechanism of action as well as, pharmacodynamics and pharmacokynetics. Moreover, we present the available literature data about the efficacy and, mainly, the safety of budesonide-MMX.

Expert opinion: budesonide-MMX is a new therapeutic option in mild-to-moderate UC patients. Its good safety profile in clinical trials undoubtedly represents a strength for a possible wide use in clinical practice, mainly if it will be confirmed by post-marketing data. Other indications, such as treatment of colonic Crohn’s disease, could theoretically be considered, if sustained by reliable scientific data.     

Electromyographic activity of masticatory, neck and trunk muscles of subjects with different skeletal facial morphology--a cross-sectional evaluation

The electromyographic pattern activity of masticatory, neck and trunk muscles was assessed using surface electromyography (sEMG) in 60 Caucasian adult females (20 subjects in skeletal class I, 20 subjects in skeletal class II and 20 subjects in skeletal class III), classified on the base of their skeletal class (ANB angle), corrected on the base of maxillary and mandibular rotations. The sEMG activity was recorded at mandibular rest position and during maximal voluntary clenching. At mandibular rest position, the sEMG activities of masseter and anterior temporal muscles were significantly higher in class III subjects than in class I and class II subjects, that showed no significant difference between them. Then, the sEMG activities of posterior cervicals and upper trapezius were significantly higher in skeletal class III subjects than in the other two groups. During maximal voluntary clenching, no significant difference was observed in the sEMG activity of masticatory muscles among the three considered groups. However, the sEMG activities of posterior cervicals and upper trapezius were significantly higher in skeletal class III subjects than in the other two groups, which showed no significant difference between them. In conclusion, the skeletal class seems to affect the sEMG pattern activity of masticatory, neck and trunk muscles.