Mortality of Patients with Hematological Malignancy after Admission to the Intensive Care Unit

Background: The admission of patients with malignancies to an intensive care unit (ICU) still remains a matter of substantial controversy. The identification of factors that potentially influence the patient outcome can help ICU professionals make appropriate decisions. Patients and Methods: 90 adult patients with hematological malignancy (leukemia 47.8%, high-grade lymphoma 50%) admitted to the ICU were analyzed retrospectively in this single-center study considering numerous variables with regard to their influence on ICU and day-100 mortality. Results: The median simplified acute physiology score (SAPS) II at ICU admission was 55 (ICU survivors 47 vs. 60.5 for non-survivors). The overall ICU mortality rate was 45.6%. With multivariate regression analysis, patients admitted with sepsis and acute respiratory failure had a significantly increased ICU mortality (sepsis odds ratio (OR) 9.12, 95% confidence interval (CI) 1.1-99.7, p = 0.04; respiratory failure OR 13.72, 95% CI 1.39-136.15, p = 0.025). Additional factors associated with an increased mortality were: high doses of catecholamines (ICU: OR 7.37, p = 0.005; day 100: hazard ratio (HR) 2.96, p < 0.0001), renal replacement therapy (day 100: HR 1.93, p = 0.026), and high SAPS II (ICU: HR 1.05, p = 0.038; day 100: HR 1.2, p = 0.027). Conclusion: The decision for or against ICU admission of patients with hematological diseases should become increasingly independent of the underlying malignant disease

A survey of medical students to assess their exposure to and knowledge of renal transplantation

BACKGROUND: Within the field of renal transplantation there is a lack of qualified and trainee surgeons and a shortage of donated organs. Any steps to tackle these issues should, in part, be aimed at future doctors. METHODS: A questionnaire was distributed to final year students at a single medical school in the UK to assess their exposure to and knowledge of renal transplantation. RESULTS: Although 46% of responding students had examined a transplant recipient, only 14% had ever witnessed the surgery. Worryingly, 9% of students believed that xenotransplantation commonly occurs in the UK and 35% were unable to name a single drug that a recipient may need to take. CONCLUSIONS: This survey demonstrates a lack of exposure to, and knowledge of, the field of renal transplantation. Recommendations to address the problems with the recruitment of surgeons and donation of organs, by targeting medical students are made

Trophy hunting certification

Adaptive certification is the best remaining option for the trophy hunting industry in Africa to demonstrate sustainable and ethical hunting practices that benefit local communities and wildlife conservation

A qualitative study of health professionals’ views on using iPads to facilitate distraction during paediatric burn dressing changes

Introduction: Distraction is a non-pharmacologic pain management technique commonly used to avert a person’s attention from procedural pain and distress during stressful procedures such as treatment after a burn injury. In recent years, computer tablets (such as iPads) have been used within paediatric burns services to facilitate distraction by way of apps, games, cartoons and videos during dressing changes. However, we know very little about health professionals’ experiences of using them in this context.Methods: The current study explored health professionals’ experiences of using iPads to facilitate distraction during paediatric burn dressing changes. Fifteen health professionals from a single paediatric burns unit were interviewed. Thematic analysis revealed two key themes: (1) the iPad is a universal panacea for distraction; and (2) trials and tribulations.Discussion: Participants considered iPads to be potentially useful and effective distraction tools, suitable for use with a wide range of patients with burn injuries including young children, adolescents and young adults. However, issues including health professionals’ understandings of one another’s roles, the challenge of working in a busy burns service, and lack of experience and confidence were identified as possible barriers to their use within routine burn care. Training for staff on the use of iPads as a means of facilitating distraction, development of guidelines and a review of how they are incorporated into routine burn care are recommended

Analysis and comparative genomics of R997, the first SXT/R391 integrative and conjugative element (ICE) of the Indian Sub-Continent

peer-reviewedThe aim of this study was to analyse R997, the first integrative and conjugative element (ICE) isolated from the Indian Sub-Continent, and to determine its relationship to the SXT/R391 family of ICEs. WGS of Escherichia coli isolate AB1157 (which contains R997) was performed using Illumina sequencing technology. R997 context was assessed by de novo assembly, gene prediction and annotation tools, and compared to other SXT/R391 ICEs. R997 has a size of 85 Kb and harbours 85 ORFs. Within one of the variable regions a HMS-1 β-lactamase resistance gene is located. The Hotspot regions of the element contains restriction digestion systems and insertion sequences. R997 is very closely related to the SXT-like elements from widely dispersed geographic areas. The sequencing of R997 increases the knowledge of the earliest isolated SXT/R391 elements and may provide insight on the emergence of these elements on the Indian sub-continent.PUBLISHEDpeer-reviewe

Differences in the signaling pathways of α1A- and α1B-adrenoceptors are related to different endosomal targeting

Aims: To compare the constitutive and agonist-dependent endosomal trafficking of α1A- and α1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods: Using CypHer5 technology and VSV-G epitope tagged α1A- and α1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions: Constitutive as well as agonist-induced trafficking of α1A and α1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: α1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to β-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. α1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-β-cyclodextrin

Seatbelt use and risk of major injuries sustained by vehicle occupants during motor-vehicle crashes: A systematic review and meta-analysis of cohort studies

BackgroundIn 2004, a World Health Report on road safety called for enforcement of measures such as seatbelt use, effective at minimizing morbidity and mortality caused by road traffic accidents. However, injuries caused by seatbelt use have also been described. Over a decade after publication of the World Health Report on road safety, this study sought to investigate the relationship between seatbelt use and major injuries in belted compared to unbelted passengers.MethodsCohort studies published in English language from 2005 to 2018 were retrieved from seven databases. Critical appraisal of studies was carried out using the Scottish Intercollegiate Guidelines Network (SIGN) checklist. Pooled risk of major injuries was assessed using the random effects meta-analytic model. Heterogeneity was quantified using I-squared and Tau-squared statistics. Funnel plots and Egger's test were used to investigate publication bias. This review is registered in PROSPERO (CRD42015020309).ResultsEleven studies, all carried out in developed countries were included. Overall, the risk of any major injury was significantly lower in belted passengers compared to unbelted passengers (RR 0.47; 95%CI, 0.29 to 0.80; I-2=99.7; P=0.000). When analysed by crash types, belt use significantly reduced the risk of any injury (RR 0.35; 95%CI, 0.24 to 0.52). Seatbelt use reduces the risk of facial injuries (RR=0.56, 95% CI=0.37 to 0.84), abdominal injuries (RR=0.87; 95% CI=0.78 to 0.98) and, spinal injuries (RR=0.56, 95% CI=0.37 to 0.84). However, we found no statistically significant difference in risk of head injuries (RR=0.49; 95% CI=0.22 to 1.08), neck injuries (RR=0.69: 95%CI 0.07 to 6.44), thoracic injuries (RR 0.96, 95%CI, 0.74 to 1.24), upper limb injuries (RR=1.05, 95%CI 0.83 to 1.34) and lower limb injuries (RR=0.77, 95%CI 0.58 to 1.04) between belted and non-belted passengers.ConclusionIn sum, the risk of most major road traffic injuries is lower in seatbelt users. Findings were inconclusive regarding seatbelt use and susceptibility to thoracic, head and neck injuries during road traffic accidents. Awareness should be raised about the dangers of inadequate seatbelt use. Future research should aim to assess the effects of seatbelt use on major injuries by crash type

Retrospective harm benefit analysis of pre-clinical animal research for six treatment interventions

The harm benefit analysis (HBA) is the cornerstone of animal research regulation and is considered to be a key ethical safeguard for animals. The HBA involves weighing the anticipated benefits of animal research against its predicted harms to animals but there are doubts about how objective and accountable this process is.i. To explore the harms to animals involved in pre-clinical animal studies and to assess these against the benefits for humans accruing from these studies; ii. To test the feasibility of conducting this type of retrospective HBA.Data on harms were systematically extracted from a sample of pre-clinical animal studies whose clinical relevance had already been investigated by comparing systematic reviews of the animal studies with systematic reviews of human studies for the same interventions (antifibrinolytics for haemorrhage, bisphosphonates for osteoporosis, corticosteroids for brain injury, Tirilazad for stroke, antenatal corticosteroids for neonatal respiratory distress and thrombolytics for stroke). Clinical relevance was also explored in terms of current clinical practice. Harms were categorised for severity using an expert panel. The quality of the research and its impact were considered. Bateson's Cube was used to conduct the HBA.The most common assessment of animal harms by the expert panel was 'severe'. Reported use of analgesia was rare and some animals (including most neonates) endured significant procedures with no, or only light, anaesthesia reported. Some animals suffered iatrogenic harms. Many were kept alive for long periods post-experimentally but only 1% of studies reported post-operative care. A third of studies reported that some animals died prior to endpoints. All the studies were of poor quality. Having weighed the actual harms to animals against the actual clinical benefits accruing from these studies, and taking into account the quality of the research and its impact, less than 7% of the studies were permissible according to Bateson's Cube: only the moderate bisphosphonate studies appeared to minimise harms to animals whilst being associated with benefit for humans.This is the first time the accountability of the HBA has been systematically explored across a range of pre-clinical animal studies. The regulatory systems in place when these studies were conducted failed to safeguard animals from severe suffering or to ensure that only beneficial, scientifically rigorous research was conducted. Our findings indicate a pressing need to: i. review regulations, particularly those that permit animals to suffer severe harms; ii. reform the processes of prospectively assessing pre-clinical animal studies to make them fit for purpose; and iii. systematically evaluate the benefits of pre-clinical animal research to permit a more realistic assessment of its likely future benefits

Monocytes regulate the mechanism of T-cell death by inducing Fas-mediated apoptosis during bacterial infection.

Monocytes and T-cells are critical to the host response to acute bacterial infection but monocytes are primarily viewed as amplifying the inflammatory signal. The mechanisms of cell death regulating T-cell numbers at sites of infection are incompletely characterized. T-cell death in cultures of peripheral blood mononuclear cells (PBMC) showed 'classic' features of apoptosis following exposure to pneumococci. Conversely, purified CD3(+) T-cells cultured with pneumococci demonstrated necrosis with membrane permeabilization. The death of purified CD3(+) T-cells was not inhibited by necrostatin, but required the bacterial toxin pneumolysin. Apoptosis of CD3(+) T-cells in PBMC cultures required 'classical' CD14(+) monocytes, which enhanced T-cell activation. CD3(+) T-cell death was enhanced in HIV-seropositive individuals. Monocyte-mediated CD3(+) T-cell apoptotic death was Fas-dependent both in vitro and in vivo. In the early stages of the T-cell dependent host response to pneumococci reduced Fas ligand mediated T-cell apoptosis was associated with decreased bacterial clearance in the lung and increased bacteremia. In summary monocytes converted pathogen-associated necrosis into Fas-dependent apoptosis and regulated levels of activated T-cells at sites of acute bacterial infection. These changes were associated with enhanced bacterial clearance in the lung and reduced levels of invasive pneumococcal disease