Does DCD Donor Time‐to‐Death Affect Recipient Outcomes? Implications of Time‐to‐Death at a High‐Volume Center in the United States

For donation after circulatory death (DCD), many centers allow 1 h after treatment withdrawal to donor death for kidneys. Our center has consistently allowed 2 h. We hypothesized that waiting longer would be associated with worse outcome. A single‐center, retrospective analysis of DCD kidneys transplanted between 2008 and 2013 as well as a nationwide survey of organ procurement organization DCD practices were conducted. We identified 296 DCD kidneys, of which 247 (83.4%) were transplanted and 49 (16.6%) were discarded. Of the 247 recipients, 225 (group 1; 91.1%) received kidneys with a time to death (TTD) of 0–1 h; 22 (group 2; 8.9%) received grafts with a TTD of 1–2 h. Five‐year patient survival was 88.8% for group 1, and 83.9% for group 2 (p = 0.667); Graft survival was also similar, with 5‐year survival of 74.1% for group 1, and 83.9% for group 2 (p = 0.507). The delayed graft function rate was the same in both groups (50.2% vs. 50.0%, p = 0.984). TTD was not predictive of graft failure. Nationally, the average maximum wait‐time for DCD kidneys was 77.2 min. By waiting 2 h for DCD kidneys, we performed 9.8% more transplants without worse outcomes. Nationally, this practice would allow for hundreds of additional kidney transplants, annually.     

Engaged,Workaholic, Burned‐Out or Just 9‐to‐5? Toward a Typology of Employee Well‐being

The aim of this study was to establish a typology of employee well‐being, together with its psychosocial antecedents and consequences. Results obtained with a sample of 786 full‐time employees from different occupational sectors show four types of employee well‐being: 9‐to‐5 or relaxed, work engaged or enthusiastic, workaholic or tense, and burned‐out or fatigued, each having different relationships with job and personal characteristics. This study provides evidence of a parsimonious, theory‐based classification of employee well‐being and contributes to the existing literature about work investment because meaningful relations were found between various types of employee well‐being, and heavy and soft work investors. Copyright © 2013 John Wiley & Sons, Ltd.     

What is behind phylogenetic analysis of hospital‐, community‐ and livestock‐associated methicillin‐resistant Staphylococcus aureus?

Methicillin‐resistant Staphylococcus aureus (MRSA) has been shown to be the predominant life‐threatening pathogen in Egypt. MRSA is a major cause of severe healthcare‐associated (HA) infections. During the last decades, the incidence of community‐associated (CA) MRSA infections has a complex epidemiology arising from the circulation of different strains in the general population. Moreover, livestock‐associated (LA) MRSA emerged recently becomes an emerging threat to public health. Therefore, it is important to illuminate the differences between CA‐, HA‐ and LA‐MRSA to shed light on their genetic diversity and evolution. This study presents the first data on analysing the correlation between CA‐, LA‐ and HA‐MRSA using antibiogram typing, molecular characteristics and antimicrobial resistance and virulence genes’ profiles. Overall, HA‐MRSA strains tended to be multidrug resistant and less virulent than both LA‐ and CA‐MRSA strains. Importantly, CA‐MRSA strains had a high homology with each of HA‐ and LA‐MRSA. However, no similarity was observed between HA‐ and LA‐MRSA. Our findings suggest that the epidemiological changes in genetic behaviour between HA‐ and LA‐MRSA are due to the presence of CA‐MRSA confirming that CA‐MRSA has created a public health crisis worldwide.     

Are N‐glycolylneuraminic acid (Hanganutziu–Deicher) antigens important in pig‐to‐human xenotransplantation?

BACKGROUND: N-glycolylneuraminic acid (NeuGc) epitopes, so called Hanganutziu-Deicher (HD) antigens, which are widely expressed on endothelial cells of all mammals except humans, are considered to be potential targets for natural and elicited anti-nonGalalpha1-3 Gal (Gal) antibodies in humans. We previously reported that anti-NeuGc antibodies were not detected in healthy humans by enzyme-linked immunosorbent assay (ELISA) using NeuGc-GM3-coated plates, and no antibody production was observed in patients with a history of exposure to pig cells. However, a recent paper has revealed that (i) anti-NeuGc antibodies to porcine red blood cells (PRBC) are detectable in most healthy humans, and (ii) the majority of anti-nonGal antibodies are specific for NeuGc epitopes. The purpose of this study was to reassess whether NeuGc is important as an immunogenic nonGal epitope. METHODS: The binding of antibodies to PRBC and porcine aortic endothelial cells (PAEC) was compared. Cells were treated with (i) alpha-galactosidase, and then (ii) neuraminidase, which digests sialic acids, including NeuGc epitopes. Cells were incubated with human pooled sera, and applied to flow cytometric analysis. After enzyme digestion, almost complete reduction of Gal and NeuGc expression was confirmed by GS-IB4 and HU/Ch2-7 (a chicken monoclonal antibody against HD antigens), respectively. Trypsin, which removes membrane glycoproteins, and endoglycoceramidase which cleaves glycolipids, were used for differentiating between NeuGc-containing glycoproteins and glycolipids. RESULTS: Neuraminidase-treatment reduced the binding of immunoglobulin G (IgG) antibodies to PRBC; about half of the anti-nonGal IgG antibodies to PRBC were directed to NeuGc. In contrast, anti-nonGal antibodies to PAEC were not directed to NeuGc. Trypsin-treatment markedly reduced the expression of NeuGc only on PRBC. Endoglycoceramidase-treatment was followed by a greater reduction in NeuGc epitopes on PAEC than on PRBC. Most NeuGc on PRBC appeared to be linked to proteins, but most NeuGc on PAEC was expressed on glycolipids. CONCLUSIONS: Carbohydrate structures on PRBC are different from those on PAEC. Healthy human sera contain anti-nonGal IgG antibodies to NeuGc expressed on PRBC, but not on PAEC. We speculate that anti-nonGal IgG antibodies to PRBC can recognize both NeuGc and protein, and this may be the reason why such antibodies have not been detected by ELISA. A definite conclusion about the immunogenicity of NeuGc has not been obtained. More sera from patients (not from non-human primates) sensitized with porcine cells or organs need to be studied.     

The Challenging Estrogen Receptor‐Negative/ Progesterone Receptor‐Negative/HER‐2‐Negative Patient: A Promising Candidate for Epidermal Growth Factor Receptor‐Targeted Therapy?

While epidermal growth factor receptor (EGFR)-targeted therapy has been very promising in a number of human malignancies, to date these targeted biologic agents have not proven effective in breast cancer. However, the EGFR tyrosinase inhibitors have been used indiscriminately against all types of breast tumors, perhaps missing a subpopulation of patients who may be prime candidates for EGFR-targeted therapy. In this communication we propose that patients with estrogen receptor (ER)-negative/progesterone receptor (PR)-negative/HER-2-negative tumors, which currently present a therapeutic challenge for the oncologist, may be the subgroup of breast cancer patients that might benefit from specific EGFR-targeted therapies.     

Long‐ or short‐acting opioids for chronic non‐malignant pain? A qualitative systematic review

In selected patients with chronic non‐malignant pain, chronic opioid therapy is indicated. Published guidelines recommend long‐acting over short‐acting opioids in these patients. The aim of this systematic review was to investigate whether long‐acting opioids in chronic non‐malignant pain are superior to short‐acting opioids in pain relief, physical function, sleep quality, quality of life or adverse events. This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. PubMed, Embase and Cochrane Central Register of Controlled Trials were searched for relevant trials up to July 2012. Reference lists of included trials and relevant reviews were in addition searched by hand. Of the 1168 identified publications, 6 randomised trials evaluating efficacy and safety filled the criteria for inclusion. None of them found a significantly better pain relief, significantly less consumption of rescue analgesia, improved quality of sleep or improved physical function from long‐acting opioids. None of the trials investigated quality of life. None of the trials investigated adverse events properly nor addiction, tolerance or hyperalgesia. Three trials in healthy volunteers with a recreational drug use, found no difference in abuse potential between long‐ and short‐acting opioids. While long term, comparative data are lacking, there is fair evidence from short‐term trials that long‐acting opioids provide equal pain relief compared with short‐acting opioids. Contrary to several guidelines, there is no evidence supporting long‐acting opioids superiority to short‐acting ones in improving functional outcomes, reducing side effects or addiction.     

On what are our end‐of‐life decisions based?

BACKGROUND: The incidence of withholding and withdrawing life support from the critically ill has increased in recent years. The aim of this study was to assess the degree of consistency between the weight assigned by intensivists to different determinants and their relation to end-of-life decisions, and to evaluate the current concepts in withholding or withdrawing intensive care in Nordic countries. METHODS: Forty-one intensivists from Nordic countries completed a questionnaire sent by e-mail: consistency between contributing factors and the decisions regarding 10 actual cases was evaluated by logistic regression analysis and by the classification (leave-one-out) method. Concepts in management after the withdrawal decision were also analyzed. RESULTS: The median (range) number of withdrawals per physician was four (range 0-10) out of 10 cases. No single factor was an independent covariant of all decisions made. The classification method revealed that approximately 70% only of decisions could be predicted correctly. Different actions taken after a decision to withdraw intensive care varied from 9.8% (discontinuing ventilator therapy) to 97.6% (informing relatives). CONCLUSIONS: No generally accepted grounds for end-of-life decisions could be detected among Nordic intensivists. In addition, the current concept of management after decision to withdraw therapy varies markedly. This study has implications in further assessment of the individual decision-making process and the uniformity of actions after withdrawal decisions.     

Pig‐to‐human heart transplantation: Who goes first?

Cardiac xenotransplantation has recently taken an important step towards clinical reality. In anticipation of the “first‐in‐human” heart xenotransplantation trial, we propose a set of patient characteristics that define potential candidates. Our premise is that, to be ethically justified, the risks posed by current state‐of‐the‐art options must outweigh the anticipated risks of a pioneering xenotransplant procedure. Suitable candidates include patients who are at high immunologic risk because of sensitization to alloantigens, including those who have exhibited early onset or accelerated cardiac allograft vasculopathy. In addition, patients should be considered (1) for whom mechanical circulatory support would be prohibitively risky due to a hypercoagulable state, a contraindication to anticoagulation, or restrictive physiology; (2) with severe biventricular dysfunction predicting unsuccessful univentricular left heart support; and (3) adults with complex congenital heart disease. In conclusion, because the published preclinical benchmark for clinical translation of heart xenotransplantation appears within reach, carefully and deliberately defining appropriate trial participants is timely as the basis for ethical clinical trial design.     

Do antioxidants inhibit oxidative‐stress‐induced autophagy of tenofibroblasts?

Recent research on tendinopathy has focused on its relationship to programmed cell death. Increased autophagy has been observed in ruptured rotator cuff tendon tissues, suggesting a causal relationship. We investigated whether autophagy occurs in human rotator cuff tenofibroblast death induced by oxidative stress and whether antioxidants protect against autophagic cell death. We used H₂O₂ (0.75 mM) as oxidative stressor, cyanidin (100 µg/ml) as antioxidant, zVAD (20 µM) as apoptosis inhibitor, and 3‐MA (10 mM) as autophagy inhibitor. We evaluated cell viability and known autophagic markers: LC3‐II expression, GFP‐LC3 puncta formation, autolysosomes, and Atg5‐12 and Beclin 1 expression. H₂O₂ exposure increased the rates of cell death, LC3‐II expression, GFP‐LC3 puncta formation, and autolysosomes. After we induced apoptosis arrest using zVAD, H₂O₂ exposure still induced cell death, LC3‐II expression, and GFP‐LC3 puncta formation. H₂O₂ exposure also increased Atg5‐12 and Beclin 1 expressions, indicating autophagic cell death. However, cyanidin treatment reduced H₂O₂‐induced cell death, LC3‐II expression, GFP‐LC3 puncta formation, and autolysosomes. Cyanidin and 3‐MA similarly reduced the cell‐death rate, and Atg5‐12 and Beclin 1 expression. This study demonstrated that H₂O₂, an oxidative stressor, induces autophagic cell death in rotator cuff tenofibroblasts, and that cyanidin, a natural antioxidant, inhibits autophagic cell death. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:937–943, 2014.     

ASDIN: Autogenous Side‐to‐Side Brachial‐Basilic Fistulas Without Vein Transposition: A Valuable Option?

An autogenous brachial‐basilic arteriovenous fistula (BBAVF) in the upper arm must be considered before placing prosthetic grafts in hemodialysis patients with multiple failures of forearm AVFs. The aim of this observational study was to compare technical and clinical outcomes of a new construction technique for BBAVF (n‐BBAVF) with that of the standard one‐stage side‐artery to end‐vein transposed BBAVF (t‐BBAVF). A n‐BBAVF is constructed in the following way: basilic vein and brachial artery are isolated. Patency of the proximal and distal vein is verified by injecting warmed (37°C) saline solution. A venotomy and an arterotomy of 4–5 mm are performed. The two vessels are prepared for a side‐to‐side anastomosis without transposition of the vein. The latter allows both an antegrade and retrograde flow along the basilic vein, both proximally and distally to the anastomosis with more sites available for the venipunctures of the dialysis. Thirty BBAVFs were constructed as the secondary or tertiary vascular access in 30 patients over a 4‐year period: 17 patients with adequate forearm basilic vein underwent the construction of a n‐BBAVF; 13 underwent the construction of a t‐BBAVF. The construction of a n‐BBAVF requires a significantly lesser surgical time (55.0 ± 9.0 minutes vs. 115.0 ± 18.0, p < 0.0001), has fewer surgical complications (5.9% vs. 46.2%, p < 0.0001), and a reduced time to first use (24.5 ± 6.3 vs. 37.7 ± 9.1 days, p < 0.0001) than that of a t‐BBAVF. n‐BBAVFs showed a relatively low rate of thrombosis per patient‐year at risk (0.067 at 1 year and 0.099 at 2 years). The latter was significantly lower at 1 year when compared with t‐BBAVFs (0.067 vs. 0.285; p < 0.004). Our policy of “all AVFs should be autogenous” led us to the construction of a vascular access which is based on a side‐to‐side anastomosis between the brachial artery and the basilic vein without transposition of the vein allowing both antegrade and retrograde flow into the basilic vein. The results of this surgical technique appear satisfactory.     

Short‐term administration of prulifloxacin in patients with nonmuscle‐invasive bladder cancer: an effective option for the prevention of bacillus Calmette‐Guérin‐induced toxicity?

OBJECTIVE

To determine whether the new fluoroquinolone prulifloxacin might improve tolerance to Bacillus Calmette‐Guérin (BCG) intravesical therapy in patients with bladder cancer.

PATIENTS AND METHODS

A series of 72 patients with intermediate‐ or high‐risk nonmuscle‐invasive bladder cancer were enrolled in this prospective, randomized, open‐label, controlled clinical trial performed at a single tertiary care institution. After complete transurethral resection, patients were randomized to receive induction treatment with BCG and three capsules of prulifloxacin 600 mg or no prophylactic treatment (control group). Adverse events (AEs) were self‐recorded by the patients after each instillation and classified by the investigator according to a classification grid considering account duration and intensity. Cystoscopy findings at 3 and 6 months were also recorded.

RESULTS

There was no significant difference in baseline symptoms between the groups. Overall, there was a significant decrease in the percentage of patients with at least one AE between instillations in prulifloxacin‐treated group. The proportion of patients with moderate to severe AEs after the fourth instillation was significantly less in the prulifloxacin‐treated group. There was a significant effect of prulifloxacin on the need for anti‐tuberculosis treatment. More patients in the control group stopped or delayed the full induction course of BCG instillations (34% vs 19%, P = 0.04). Recurrence rates were not affected by prulifloxacin treatment.

CONCLUSION

Prulifloxacin reduces the incidence of moderate to severe AEs from BCG intravesical therapy in patients with nonmuscle‐invasive bladder cancer, improving compliance to the induction BCG course. These preliminary findings warrant further clinical research.