Organ donor screening for carbapenem‐resistant gram‐negative bacteria in Italian intensive care units: the DRIn study

The 759 cases of brain death declaration (BDD [Italian law, 6 hours of observation time]) that occurred in 190 Italian intensive care units (ICUs) between May and September 2012 were studied to quantify carbapenem‐resistant gram‐negative bacteria (CR‐GN) isolated in organ donors, to evaluate adherence to national screening guidelines, and to identify risk factors for CR‐GN isolation. Mandatory blood, bronchoalveolar lavage, and urine cultures were performed on the BDD day in 99% of used donors. Because results were rarely made available before transplant, >20% of transplants were performed before obtaining any microbiological information, and organs from 15 of 22 CR‐GN cases were used. Two (lung–liver) of the 37 recipients died, likely because of donor‐derived early CR‐GN sepsis. ICU stay >3 days (odds ratio [OR] = 7.49, P = .004), fever (OR = 3.11, P = .04), age <60 years (OR = 2.80, P = .06), and positive ICU epidemiology (OR = 8.77, P = .07) were associated with CR‐GN isolation. An association between single ICU and risk of CR‐GN was observed, as a result of differences across ICUs (ICC = 29%; 95% confidence interval [CI] 6.5%‐72%) probably related to inadequate practices of infection control. Continuous education aimed at implementing priority actions, including stewardship programs for a rational use of antimicrobials, is a priority in healthcare systems and transplant networks. Improved awareness among ICU personnel regarding the importance of early CR‐GN detection and timely alert systems might facilitate decisions regarding organ suitability and eventually save recipient lives.     

Cutaneous adverse reactions linked to targeted anticancer therapies bortezomib and lenalidomide for multiple myeloma: new drugs,old side effects

Context: Cutaneous toxicity is a frequent side effect of new anticancer targeted therapies. Skin reactions can severely impact the patient’s physical, psychological and social well-being and may sometimes lead to discontinuations either treatment dose reductions.

Objective: This study evaluates the impact of cutaneous adverse drug reactions (cADR) of the new therapies bortezomib and lenalidomide and presents a review of their skin side effects.

Materials and method: Type, frequency, severity, time of onset and management of cADR were collected and the medical records of all multiple myeloma patients receiving bortezomib or lenalidomide in the Hematology and Medical Oncology Institute of the University of Bologna, were analyzed.

Results: A total of 17 cADR occurred in 10 patients of 17 (58.8% of patients) treated with bortezomib: 5 rashes, 3 events of pruriginous rash, 1 purpuric rash, 2 records of mouth swelling, 1 stomatitis-mucositis, 3 cases of edema in the lower limbs, 1 patient referred pruritus and another telogen effluvium. Eight skin manifestations were due to lenalidomide in 7 patients of 25 treated (28%): 2 pruriginous rashes, 3 cases of edema, 2 records of pruritus, 1 case of stomatitis-mucositis. Three adverse events linked to bortezomib and 4 to lenalidomide forced to a complete withdrawal of the drug, while 3 reactions due to bortezomib mandated a dose reduction. Dermatological evaluation was performed only in 2 patients treated with bortezomib and 1 with lenalidomide.

Discussion: Evaluations of cADR due to bortezomib and lenalidomide were performed. There are no other reports focused on skin events in patients treated with the triple regimen velcade (bortezomib)-thalidomide-dexamethasone (VTD) up to date. Our study suggests that cutaneous toxicities, when researched by Dermatologists, are a side effect even more frequent than the reported data.

Limitations: As it is a single institute and retrospective study, ongoing cADR were rarely evaluated by dermatologists; thus, it is possible that cutaneous reactions (especially mild) may have been under reported by Hematologists and Oncologists in clinical records.

Conclusions: Even with the development of new drugs for cancer treatment, “old” cutaneous side effects may still be present, compromising patients’ quality of life. Physicians prescribing bortezomib and lenalidomide should monitor their patients for the spectrum of cADR, and they should involve dermatologists in consultations and management of these events. A multidisciplinar approach is necessary to oncologic patient in order to provide a tailored supportive clinical care.     

Nd:YAG laser as an adjunctive treatment to nonsurgical periodontal therapy

A meta-analysis was conducted to investigate whether the use of Nd:YAG laser adjunctive to scaling root planing (SRP) could provide additional benefits compared to SRP alone in patients with chronic periodontitis. The meta-analysis was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) statement and the recommendations of the Cochrane Collaboration. A literature search was performed on seven databases, followed by a manual search. Weighted mean differences and 95 % confidence intervals were calculated for the clinical attachment level (CAL), probing depth (PD), and changes in plaque index (PI) and gingival crevicular fluid (GCF). Inter-study heterogeneity was assessed by the I ² test, and publication bias was analyzed by the visual inspection of the funnel plot for asymmetry, Egger’s regression test, and trim-and-fill method. All outcomes were evaluated from baseline to the end of follow-up. Significant differences in PD and GCF reduction were observed in favor of SRP?+?Nd:YAG; no significant differences were observed in CAL gain or PI change. The findings of this meta-analysis suggest that use of the Nd:YAG laser as an adjunctive therapy to conventional nonsurgical periodontal therapy could potentially provide additional benefits. However, all included studies were not at low risk of bias, and only three studies were included in the meta-analysis. As a result, the evidence is insufficient to support the effectiveness of adjunctive Nd:YAG to SRP. Future long-term well-designed parallel randomized clinical trials are required to assess the effectiveness of the adjunctive use of Nd:YAG laser. These trials should also include microbiological and adverse events analyses.     

5‐S‐cysteinyldopamine neurotoxicity: Influence on the expression of α‐synuclein and ERp57 in cellular and animal models of Parkinson's disease

Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is still unclear in spite of extensive investigations. It has been hypothesized that 5‐S‐cysteinyldopamine (CysDA), a catechol‐thioether metabolite of dopamine (DA), could be an endogenous parkinsonian neurotoxin. To gain further insight into its role in the neurodegenerative process, both CD1 mice and SH‐SY5Y neuroblastoma cells were treated with CysDA, and the data were compared with those obtained by the use of 6‐hydroxydopamine, a well‐known parkinsonian mimetic. Intrastriatal injection of CysDA in CD1 mice caused a long‐lasting depletion of DA, providing evidence of in vivo neurotoxicity of CysDA. Both in mice and in SH‐SY5Y cells, CysDA treatment induced extensive oxidative stress, as evidenced by protein carbonylation and glutathione depletion, and affected the expression of two proteins, α‐synuclein (α‐Syn) and ERp57, whose levels are modulated by oxidative insult. Real‐time PCR experiments support these findings, indicating an upregulation of both ERp57 and α‐Syn expression. α‐Syn aggregation was also found to be modulated by CysDA treatment. The present work provides a solid background sustaining the hypothesis that CysDA is involved in parkinsonian neurodegeneration by inducing extensive oxidative stress and protein aggregation. © 2013 Wiley Periodicals, Inc.     

Anticholinergic drugs rescue synaptic plasticity in DYT1 dystonia: Role of M1 muscarinic receptors

Broad‐spectrum muscarinic receptor antagonists have represented the first available treatment for different movement disorders such as dystonia. However, the specificity of these drugs and their mechanism of action is not entirely clear. We performed a systematic analysis of the effects of anticholinergic drugs on short‐ and long‐term plasticity recorded from striatal medium spiny neurons from DYT1 dystonia knock‐in (Tor1a^+/Δgag) mice heterozygous for ΔE‐torsinA and their controls (Tor1a^+/+ mice). Antagonists were chosen that had previously been proposed to be selective for muscarinic receptor subtypes and included pirenzepine, trihexyphenydil, biperiden, orphenadrine, and a novel selective M₁ antagonist, VU0255035. Tor1a^+/Δgag mice exhibited a significant impairment of corticostriatal synaptic plasticity. Anticholinergics had no significant effects on intrinsic membrane properties and on short‐term plasticity of striatal neurons. However, they exhibited a differential ability to restore the corticostriatal plasticity deficits. A complete rescue of both long‐term depression (LTD) and synaptic depotentiation (SD) was obtained by applying the M₁‐preferring antagonists pirenzepine and trihexyphenidyl as well as VU0255035. Conversely, the nonselective antagonist orphenadrine produced only a partial rescue of synaptic plasticity, whereas biperiden and ethopropazine failed to restore plasticity. The selectivity for M₁ receptors was further demonstrated by their ability to counteract the M₁‐dependent potentiation of N‐methyl‐d ‐aspartate (NMDA) current recorded from striatal neurons. Our study demonstrates that selective M₁ muscarinic receptor antagonism offsets synaptic plasticity deficits in the striatum of mice with the DYT1 dystonia mutation, providing a potential mechanistic rationale for the development of improved antimuscarinic therapies for this movement disorder. © 2014 International Parkinson and Movement Disorder Society     

Meta-Analysis of Drainage Versus No Drainage After Laparoscopic Cholecystectomy

Background and Objectives:

Routine drainage after laparoscopic cholecystectomy is still controversial. This meta-analysis was performed to assess the role of drains in reducing complications in laparoscopic cholecystectomy.

Methods:

An electronic search of Medline, Science Citation Index Expanded, Scopus, and the Cochrane Library database from January 1990 to June 2013 was performed to identify randomized clinical trials that compare prophylactic drainage with no drainage in laparoscopic cholecystectomy. The odds ratio for qualitative variables and standardized mean difference for continuous variables were calculated.

Results:

Twelve randomized controlled trials were included in the meta-analysis, involving 1939 patients randomized to a drain (960) versus no drain (979). The morbidity rate was lower in the no drain group (odds ratio, 1.97; 95% confidence interval, 1.26 to 3.10; P = .003). The wound infection rate was lower in the no drain group (odds ratio, 2.35; 95% confidence interval, 1.22 to 4.51; P = .01). Abdominal pain 24 hours after surgery was less severe in the no drain group (standardized mean difference, 2.30; 95% confidence interval, 1.27 to 3.34; P < .0001). No significant difference was present with respect to the presence and quantity of subhepatic fluid collection, shoulder tip pain, parenteral ketorolac consumption, nausea, vomiting, and hospital stay.

Conclusion:

This study was unable to prove that drains were useful in reducing complications in laparoscopic cholecystectomy.     

Dry Sliding Behavior of an Aluminum Alloy after Innovative Hard Anodizing Treatments

This work evaluates the dry sliding behavior of anodic aluminum oxides (AAO) formed during one traditional hard anodizing treatment (HA) and two golden hard anodizing treatments (named G and GP, respectively) on a EN AW-6060 aluminum alloy. Three different thicknesses of AAO layers were selected: 25, 50, and 100 μm. Prior to wear tests, microstructure and mechanical properties were determined by scanning electron microscopy (VPSEM/EDS), X-ray diffractometry, diffuse reflectance infrared Fourier transform (DRIFT-FTIR) spectroscopy, roughness, microhardness, and scratch tests. Wear tests were carried out by a pin-on-disc tribometer using a steel disc as the counterpart material. The friction coefficient was provided by the equipment. Anodized pins were weighed before and after tests to assess the wear rate. Worn surfaces were analyzed by VPSEM/EDS and DRITF-FTIR. Based on the results, the GP-treated surfaces with a thickness of 50 μm exhibit the lowest friction coefficients and wear rates. In any case, a tribofilm is observed on the wear tracks. During sliding, its detachment leads to delamination of the underlying anodic aluminum oxides and to abrasion of the aluminum substrate. Finally, the best tribological performance of G- and GP-treated surfaces may be related to the existence of a thin Ag-rich film at the coating/aluminum substrate interfaces.     

Antiviral Activity of the G-Quadruplex Ligand TMPyP4 against Herpes Simplex Virus-1

The herpes simplex virus 1 (HSV-1) genome is extremely rich in guanine tracts that fold into G-quadruplexes (G4s), nucleic acid secondary structures implicated in key biological functions. Viral G4s were visualized in HSV-1 infected cells, with massive virus cycle-dependent G4-formation peaking during viral DNA replication. Small molecules that specifically interact with G4s have been shown to inhibit HSV-1 DNA replication. We here investigated the antiviral activity of TMPyP4, a porphyrin known to interact with G4s. The analogue TMPyP2, with lower G4 affinity, was used as control. We showed by biophysical analysis that TMPyP4 interacts with HSV-1 G4s, and inhibits polymerase progression in vitro; in infected cells, it displayed good antiviral activity which, however, was independent of inhibition of virus DNA replication or entry. At low TMPyP4 concentration, the virus released by the cells was almost null, while inside the cell virus amounts were at control levels. TEM analysis showed that virus particles were trapped inside cytoplasmatic vesicles, which could not be ascribed to autophagy, as proven by RT-qPCR, western blot, and immunofluorescence analysis. Our data indicate a unique mechanism of action of TMPyP4 against HSV-1, and suggest the unprecedented involvement of currently unknown G4s in viral or antiviral cellular defense pathways.     

Nursing profession and nurses' contribution to nursing education as seen through students' eyes: A qualitative study

The behavior of clinical instructors, as observed by students, deeply influences their professional development. When instructors behave unprofessionally, they risk undermining the professional growth students gain from their clinical placement experience. Clinical instructors need to be aware of how their behavior can affect the students' learning process and the contributions they make to clinical nursing education. A qualitative study was performed to describe the nursing profession as perceived by students who observed their clinical instructors' behaviors during the clinical experience. In‐depth interviews of nursing students were conducted until data saturation was attained. Sixteen interviews were analyzed using an inductive content analysis methodology. The nursing profession was described by the participants through five themes as follows: the helping relationship, technical role, professional growth, working group, and contradictions and conflicts. Several examples of unprofessional behaviors on the part of the clinical instructors were reported by the respondents. The nursing profession, as perceived by nursing students, does not always reflect their expectations and their ideas related to professionalism. Universities and schools of nursing should ascertain that clinical instructors are prepared to educate students. Faculty should clearly state to students what they can expect from the clinical experience, namely, preparing students to face real working environments that do not always reflect educational philosophies.