Factors that influence magnetic orientation in Caenorhabditis elegans.

Magnetoreceptive animals orient to the earth's magnetic field at angles that change depending on temporal, spatial, and environmental factors such as season, climate, and position within the geomagnetic field. How magnetic migratory preference changes in response to internal or external stimuli is not understood. We previously found that Caenorhabditis elegans orients to magnetic fields favoring migrations in one of two opposite directions. Here we present new data from our labs together with replication by an independent lab to test how temporal, spatial, and environmental factors influence the unique spatiotemporal trajectory that worms make during magnetotaxis. We found that worms gradually change their average preferred angle of orientation by ~ 180° to the magnetic field during the course of a 90-min assay. Moreover, we found that the wild-type N2 strain prefers to orient towards the left side of a north-facing up, disc-shaped magnet. Lastly, similar to some other behaviors in C. elegans, we found that magnetic orientation may be more robust in dry conditions (< 50% RH). Our findings help explain why C. elegans accumulates with distinct patterns during different periods and in differently shaped magnetic fields. These results provide a tractable system to investigate the behavioral genetic basis of state-dependent magnetic orientation.

Guidelines for Perioperative Care in Elective Colorectal Surgery: Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018.

BACKGROUND: This is the fourth updated Enhanced Recovery After Surgery (ERAS®) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded recommendations for each ERAS item within the ERAS® protocol. METHODS: A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. RESULTS: All recommendations on ERAS® protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly. CONCLUSIONS: The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS® Society in this comprehensive consensus review.

Ascorbic acid ameliorates renal injury in a murine model of contrast-induced nephropathy.

BACKGROUND: Contrast induced nephropathy (CIN) is the commonest cause of iatrogenic renal injury and its incidence has increased with the advent of complex endovascular procedures. Evidence suggests that ascorbic acid (AA) has a nephroprotective effect in percutaneous coronary interventions when contrast media are used. A variety of biomarkers (NGAL, NGAL:creatinine, mononuclear cell infiltration, apoptosis and RBP-4) in both the urine and kidney were assayed using a mouse model of CIN in order to determine whether AA can reduce the incidence and/or severity of renal injury. METHODS: Twenty-four BALB/c mice were divided into 4 groups. Three groups were exposed to high doses of contrast media (omnipaque) in a well-established model of CIN, and then treated with low or high dose AA or placebo (saline). CIN severity was determined by measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL):creatinine at specific time intervals. Histological analysis was performed to determine the level of mononuclear inflammatory infiltration as well as immunohistochemistry to determine apoptosis in the glomeruli by staining for activated caspase-3 and DNA nicking (TUNEL assays). Reverse transcriptase PCR (rtPCR) of mRNA transcripts prepared from mRNA extracted from mouse kidneys was also performed for both lipocalin-2 (Lcn2) encoding NGAL and retinol binding protein-6 (RBP4) genes. NGAL protein expression was also confirmed by ELISA analysis of kidney lysates. RESULTS: Urinary NGAL:creatinine ratio was significantly lower at 48 h with a 44% and 62% (204.3µg/mmol versus 533.6µg/mmol, p = 0.049) reduction in the low and high dose AA groups, respectively. The reduced urinary NGAL:creatinine ratio remained low throughout the time period assessed (up to 96 h) in the high dose AA group. In support of the urinary analysis ELISA analysis of NGAL in kidney lysates also showed a 57% reduction (12,576 ng/ml versus 29,393 ng/ml) reduction in the low dose AA group. Immunohistochemistry for apoptosis demonstrated decreased TUNEL and caspase-3 expression in both low and high dose AA groups. CONCLUSIONS: Ascorbic acid reduced the frequency and severity of renal injury in this murine model of CIN. Further work is required to establish whether AA can reduce the incidence of CIN in humans undergoing endovascular procedures.

Mid-term cost-effectiveness analysis of open and endovascular repair for ruptured abdominal aortic aneurysm.

BACKGROUND: Emergency endovascular repair (EVAR) for ruptured abdominal aortic aneurysm (rAAA) may have lower operative mortality rates than open surgical repair. Concerns remain that the early survival benefit after EVAR for rAAA may be offset by late reinterventions. The aim of this study was to compare reintervention rates and cost-effectiveness of EVAR and open repair for rAAA. METHODS: A retrospective analysis was undertaken of patients with rAAA undergoing EVAR or open repair over 6 years. A health economic model developed for the cost-effectiveness of elective EVAR was used in the emergency setting. RESULTS: Sixty-two patients (mean age 77·9 years) underwent EVAR and 85 (mean age 75·9 years) had open repair of rAAA. Median follow-up was 42 and 39 months respectively. There was no significant difference in 30-day mortality rates after EVAR and open repair (18 and 26 per cent respectively; P = 0·243). Reintervention rates were also similar (32 and 31 per cent; P = 0·701). The mean cost per patient was €26,725 for EVAR and €30,297 for open repair, and the cost per life-year gained was €7906 and €9933 respectively (P = 0·561). Open repair had greater initial costs: longer procedural times (217 versus 178·5 min; P < 0·001) and intensive care stay (5·0 versus 1·0 days; P = 0·015). Conversely, EVAR had greater reintervention (€156,939 versus €35,335; P = 0·001) and surveillance (P < 0·001) costs. CONCLUSION: There was no significant difference in reintervention rates after EVAR or open repair for rAAA. EVAR was as cost-effective at mid-term follow-up. The increased procedural costs of open repair are not outweighed by greater surveillance and reintervention costs after EVAR.

Survival following ruptured abdominal aortic aneurysm before and during the IMPROVE Trial: a single-centre series.

OBJECTIVES: The first large-scale randomised trial (Immediate Management of the Patient with Rupture: Open Versus Endovascular repair [IMPROVE]) for endovascular repair of ruptured abdominal aortic aneurysm (rEVAR) has recently finished recruiting patients. The aim of this study was to examine the impact on survival after rEVAR when the IMPROVE protocol was initiated in a high volume abdominal aortic aneurysm (AAA) centre previously performing rEVAR. METHODS: One hundred and sixty-nine patients requiring emergency infrarenal AAA repair from January 2006 to April 2013 were included. Eighty-four patients were treated before (38 rEVAR, 46 open) and 85 (31 rEVAR, 54 open) were treated during the trial period. A retrospective analysis was performed. RESULTS: Before the trial, there was a significant survival benefit for rEVAR over open repair (90-day mortality 13% vs. 30%, p = .04, difference remained significant up to 2 years postoperatively). This survival benefit was lost after starting randomisation (90-day mortality 35% vs. 33%, p = .93). There was an increase in overall 30-day mortality from 15% to 31% (p = .02), while there was no change for open repair (p = .438). There was a significant decrease in general anaesthetic use (p = .002) for patients treated during the trial. Randomised patients had shorter hospital and intensive treatment unit stays (p = .006 and p = .03 respectively). CONCLUSIONS: The change in survival seen during the IMROVE trial highlights the need for randomised rather than cohort data to eliminate selection bias. These results from a single centre reinforce those recently reported in IMPROVE.

Meta-analysis of contemporary short- and long-term mortality rates in patients diagnosed with critical leg ischaemia.

BACKGROUND: Critical leg ischaemia (CLI) has been associated with high mortality rates. There is a lack of contemporary data on both short- and long-term mortality rates in patients diagnosed with CLI. METHODS: This was a systematic literature search for studies prospectively reporting mortality in patients diagnosed with CLI. Meta-analysis and meta-regression models were developed to determine overall mortality rates and specific patient-related factors that were associated with death. RESULTS: A total of 50 studies were included in the analysis The estimated probability of all-cause mortality in patients with CLI was 3·7 per cent at 30 days, 17·5 per cent at 1 year, 35·1 per cent at 3 years and 46·2 per cent at 5 years. Men had a statistically significant survival benefit at 30 days and 3 years. The presence of ischaemic heart disease, tissue loss and older age resulted in a higher probability of death at 3 years. CONCLUSION: Early mortality rates in patients diagnosed with CLI have improved slightly compared with previous historical data, but long-term mortality rates are still high.

Functional outcomes following revascularisation for critical limb ischaemia.

OBJECTIVES: More traditional outcome measures following lower limb bypass procedures are poor predictors of functional outcome. This paper aimed to review the effect of infrainguinal bypass surgery on residential and mobility status in patients with critical limb ischaemia. DESIGN: Review. METHODS: A Medline search up until April 2011 was undertaken of all studies involving patients with CLI undergoing ILLB and PTA. Studies were reviewed if they addressed the ambulatory/residential status of the patients pre- and post-operatively. Ambulatory status was defined as the ability to walk even with the help of a stick/frames. Independent residential status was defined as living at home with no help. RESULTS: A total of 10 studies on IILB were deemed suitable for inclusion in the review, reporting 3381 patients (2064 men). Median age ranged from 66 years to 84 years. Thirty day mortality ranged from 0% to 6.3%. Follow-up ranged from 30 days to 1 year. Three studies noted an improvement in ambulation status. No study reported any improvement in residential status after ILLB. Only one study reported on specific improvements in ambulatory status in patients with CLI after PTA. CONCLUSIONS: ILLB for patients with CLI is not without risk. Patients are not as independent or mobile following surgery. Further studies need to firstly identify the cause(s) of this and to determine optimal methods to return more patients to independence. Furthermore, CLI studies need to routinely report data on functionality.

A forensic investigation into the etiology of bat mortality at a wind farm: barotrauma or traumatic injury?

Migrating bats have increased mortality near moving turbine blades at wind farms. The authors evaluated competing hypotheses of barotrauma and traumatic injury to determine the cause. They first examined the utility of lungs from salvaged bat carcasses for histopathologic diagnosis of barotrauma and studied laboratory mice as a model system. Postmortem time, environmental temperature, and freezing of carcasses all affected the development of vascular congestion, hemorrhage, and edema. These common tissue artifacts mimicked the diagnostic criteria of pulmonary barotrauma; therefore, lung tissues from salvaged bats should not be used for barotrauma diagnosis. The authors next compared wind farm (WF) bats to building collision (BC) bats collected near downtown Chicago buildings. WF bats had an increased incidence in fracture cases and specific bone fractures and had more external lacerations than BC bats. WF bats had additional features of traumatic injury, including diaphragmatic hernia, subcutaneous hemorrhage, and bone marrow emboli. In summary, 73% (190 of 262) of WF bats had lesions consistent with traumatic injury. The authors then examined for ruptured tympana, a sensitive marker of barotrauma in humans. BC bats had only 1 case (2%, 1 of 42), but this was attributed to concurrent cranial fractures, whereas WF bats had a 20% (16 of 81) incidence. When cases with concurrent traumatic injury were excluded, this yielded a small fraction (6%, 5 of 81) of WF bats with lesions possibly consistent with barotrauma etiology. Forensic pathology examination of the data strongly suggests that traumatic injury is the major cause of bat mortality at wind farms and, at best, barotrauma is a minor etiology.

Coagulopathy associated with massive cell salvage transfusion following aortic surgery.

Cell saver blood is used within the peri-operative setting of cardiothoracic surgery to reduce the need for transfusion of allogenic blood products. Several meta-analyses have proven a significant decrease in allogenic transfusion with the use of cell salvage techniques. Washing of red cells by the cell saver and subsequent transfusion of suspended red cells can occasionally cause coagulopathy, particularly when using high concentration heparin saline to wash the spilled blood. We present the case of a 74-year-old female who underwent complicated aortic surgery and was transfused large volumes of cell-saved blood due to post-operative bleeding, which subsequently led to coagulopathy.

Early exposure to nonlethal predation risk by size-selective predators increases somatic growth and decreases size at adulthood in three-spined sticklebacks.

Predation has an important influence on life history traits in many organisms, especially when they are young. When cues of trout were present, juvenile sticklebacks grew faster. The increase in body size as a result of exposure to cues of predators was adaptive because larger individuals were more likely to survive predation. However, sticklebacks that had been exposed to cues of predators were smaller at adulthood. This result is consistent with some life history theory. However, these results prompt an alternative hypothesis, which is that the decreased size at adulthood reflects a deferred cost of early rapid growth. Compared to males, females were more likely to survive predation, but female size at adulthood was more affected by cues of predators than male size at adulthood, suggesting that size at adulthood might be more important to male fitness than to female fitness.

Meta-analysis of goal-directed fluid therapy using transoesophageal Doppler monitoring in patients undergoing elective colorectal surgery.

Background: Intraoperative goal-directed fluid therapy (GDFT) is recommended in most perioperative guidelines for intraoperative fluid management in patients undergoing elective colorectal surgery. However, the evidence in elective colorectal surgery alone is not well established. The aim of this meta-analysis was to compare the effects of GDFT with those of conventional fluid therapy on outcomes after elective colorectal surgery. Methods: A meta-analysis of RCTs examining the role of transoesophageal Doppler-guided GDFT with conventional fluid therapy in adult patients undergoing elective colorectal surgery was performed in accordance with PRISMA methodology. The primary outcome measure was overall morbidity, and secondary outcome measures were length of hospital stay, time to return of gastrointestinal function, 30-day mortality, acute kidney injury, and surgical-site infection and anastomotic leak rates. Results: A total of 11 studies were included with a total of 1113 patients (556 GDFT, 557 conventional fluid therapy). There was no significant difference in any clinical outcome measure studied between GDFT and conventional fluid therapy, including overall morbidity (risk ratio (RR) 0·90, 95 per cent c.i. 0·75 to 1·08, P = 0·27; I 2 = 47 per cent; 991 patients), 30-day mortality (RR 0·67, 0·23 to 1·92, P = 0·45; I 2 = 0 per cent; 1039 patients) and length of hospital stay (mean difference 0·01 (95 per cent c.i. -0·92 to 0·94) days, P = 0·98; I 2 = 34 per cent; 1049 patients). Conclusion: This meta-analysis does not support the perceived benefits of GDFT guided by transoesophageal Doppler monitoring in the setting of elective colorectal surgery.

Major abdominal surgery in Jehovah's Witnesses.

Introduction Patients who are Jehovah's Witnesses pose difficult ethical and moral dilemmas for surgeons because of their refusal to receive blood and blood products. This article outlines the personal experiences of six Jehovah's Witnesses who underwent major abdominal surgery at a single institution and also summarises the literature on the perioperative care of these patients. Methods The patients recorded their thoughts and the dilemmas they faced during their surgical journey. We also reviewed the recent literature on the ethical principles involved in treating such patients and strategies recommended to make surgery safer. Results All patients were supported in their decision making by the clinical team and the Hospital Liaison Committee for Jehovah's Witnesses. The patients recognised the ethical and moral difficulties experienced by clinicians in this setting. However, they described taking strength from their belief in Jehovah. A multitude of techniques are available to minimise the risk associated with major surgery in Jehovah's Witness patients, many of which have been adopted to minimise unnecessary use of blood products in general. Nevertheless, the risks of catastrophic haemorrhage and consequent mortality remain an unresolved issue for the treating team. Conclusions Respect for a patient's autonomy in this setting is the overriding ethical principle, with detailed discussion forming an important part of the preparation of a Jehovah's Witness for major abdominal surgery. Clinicians must be diligent in the documentation of the patient's wishes to ensure all members of the team can abide by these.

Management of rib fractures in traumatic flail chest: a meta-analysis of randomised controlled trials.

AIMS: Flail chest from a blunt injury to the thorax is associated with significant morbidity and mortality. Its management globally is predominantly non-operative; however, there are an increasing number of centres which undertake surgical stabilisation. The aim of this meta-analysis was to compare the efficacy of this approach with that of non-operative management. PATIENTS AND METHODS: A systematic search of the literature was carried out to identify randomised controlled trials (RCTs) which compared the clinical outcome of patients with a traumatic flail chest treated by surgical stabilisation of any kind with that of non-operative management. RESULTS: Of 1273 papers identified, three RCTs reported the results of 123 patients with a flail chest. Surgical stabilisation was associated with a two thirds reduction in the incidence of pneumonia when compared with non-operative management (risk ratio 0.36, 95% confidence interval (CI) 0.15 to 0.85, p = 0.02). The duration of mechanical ventilation (mean difference -6.30 days, 95% CI -12.16 to -0.43, p = 0.04) and length of stay in an intensive care unit (mean difference -6.46 days, 95% CI 9.73 to -3.19, p = 0.0001) were significantly shorter in the operative group, as was the overall length of stay in hospital (mean difference -11.39, 95% CI -12.39 to -10.38, p < 0.0001). CONCLUSION: Surgical stabilisation for a traumatic flail chest is associated with significant clinical benefits in this meta-analysis of three relatively small RCTs. Cite this article: Bone Joint J 2016;98-B:1119-25.

Antibiotic prophylaxis in orthopaedic surgery: difficult decisions in an era of evolving antibiotic resistance.

Prophylactic antibiotics can decrease the risk of wound infection and have been routinely employed in orthopaedic surgery for decades. Despite their widespread use, questions still surround the selection of antibiotics for prophylaxis, timing and duration of administration. The health economic costs associated with wound infections are significant, and the judicious but appropriate use of antibiotics can reduce this risk. This review examines the evidence behind commonly debated topics in antibiotic prophylaxis and highlights the uses and advantages of some commonly used antibiotics. Cite this article: Bone Joint J 2016;98-B:1014-19.

PET-CT offers accurate assessment of tumour length in oesophageal malignancy.

INTRODUCTION: Radiotherapy is increasingly used for both curative and palliative treatment of oesophageal malignancy. Accurate treatment depends on determining tumour location and length. This study assessed the value of PET-CT versus other staging modalities in determining tumour length. MATERIALS AND METHODS: Oesophageal cancer patients who underwent staging with PET/CT and endoscopic ultrasound (EUS) in addition to their diagnostic upper GI endoscopy and subsequent surgical resection were assessed. PET/CT length was obtained retrospectively by using Hermes Hybrid Viewer™ with a 1-5 Standardised Uptake Value grey scale. An SUV of 5 was used as the cut off for determining length. Direct measurement by EUS and OGD were determined. RESULTS: 53 patients underwent PET-CT, EUS, OGD and surgical resection for oesophageal cancer. Overall the correlation between PET-CT and histopathological length was strongest (Pearson r=0.5977, 95% CI 0.390-0.747) versus EUS (Pearson R=0.5365, 95% CI 0.311-0.705) and OGD (Pearson r=0.1574, 95% CI -0.118 to 0.410). After excluding tumours with a significant chemotherapy response, PET-CT length correlated significantly with histopathological length (R=0.5651, p=0.0005). In comparison, the correlation between histological length and EUS (R=0.4637, p=0.0057) measurement was less significant and this did not correlate with OGD (R=-0.1084, p=0.5417). CONCLUSION: Tumour length estimated by PET-CT correlated most strongly with histopathological length of oesophageal malignancy and is the most accurate determinant of tumour length of all the staging modalities. This suggests a potential role for PET-CT in the planning of radiotherapy and resection, particularly when considering the practical limitations of EUS.

Relaxant effect of U0126 in hemolysate-, oxyhemoglobin-, and bloody cerebrospinal fluid-induced contraction in rabbit basilar artery.

BACKGROUND AND PURPOSE: It has been suggested that mitogen-activated protein kinase (MAPK) is involved in cerebral vasospasm after subarachnoid hemorrhage. The present study was undertaken to explore the inhibitory effect of U0126, a novel MAPK inhibitor, in the contraction of the rabbit basilar artery by 3 spasmogens: hemolysate, oxyhemoglobin, and bloody cerebrospinal fluid (CSF) from patients with vasospasm. METHODS: The contraction and relaxation of rabbit basilar arteries were measured by isometric tension. MAPK immunoprecipitation was assessed by Western blot analysis. RESULTS: (1) Pretreatment of the rabbit basilar arteries with U0126 reduced contractions to hemolysate, oxyhemoglobin, or bloody CSF applied subsequently. (2) In the absence of endothelial cells, U0126 produced an inhibitory effect similar to the contractions induced by hemolysate, oxyhemoglobin, or bloody CSF. (3) U0126 relaxed the sustained contraction induced by hemolysate, oxyhemoglobin, or bloody CSF. (4) Hemolysate, oxyhemoglobin, and bloody CSF enhanced MAPK immunoprecipitation. (5) U0126 reduced MAPK immunoprecipitation induced by hemolysate, oxyhemoglobin, and bloody CSF. (6) Hemolysate, oxyhemoglobin, and bloody CSF significantly increased MAPK activity in the rabbit basilar artery. (7) U0126 abolished the effect of hemolysate, oxyhemoglobin, or bloody CSF on MAPK activation. CONCLUSIONS: This study demonstrated a role of MAPK in the contraction of rabbit basilar arteries by hemolysate, oxyhemoglobin, and bloody CSF. MAPK inhibitor U0126 may be useful in the treatment of cerebral vasospasm.

The role of the physician in effecting change in hospital charge for radical prostatectomy.

BACKGROUND: Continuing effort is being made to provide the best medical care in a cost-effective manner, requiring an evaluation of factors that control charges. The number of cases of carcinoma of the prostate gland and the number of radical retropubic prostatectomies performed have increased in recent years, with an estimate of several hundred million dollars being spent annually on this procedure in the United States of America. Because physicians are reported to effect the majority of charges for a hospitalization, this study examines the influence of notification of the physician of hospital charges on the overall hospital charges for radical retropubic prostatectomy. STUDY DESIGN: Total hospital charge and duration per hospitalization were determined for all patients having radical prostatectomies performed at five community hospitals in Richmond, VA, between January 1991 and December 1993. Patients included 625 males diagnosed with carcinoma of the prostate gland undergoing radical prostatectomy by one of 20 urologists from several different private practice groups. Halfway into the time period studied, physicians were notified of data collection and of factors that seemed to have a role in hospital charges. Total hospital charges before and after physician notification were measured to determine whether or not physicians could effect hospital charges. RESULTS: Overall, hospital charges decreased significantly after notification of physicians in the study. The decline in total charges continued throughout the follow-up period. Duration of hospitalization decreased throughout the entire study period, while total charge per hospital day increased. CONCLUSIONS: Physician awareness of hospital charges for operative procedures and accompanying hospitalizations may influence the overall decrease in charges.

A GC/MS method for the determination of 4,4'-diaminodiphenylmethane and substituted analogues in urine.

A sensitive and specific gas chromatography/mass spectrometry (GC/MS) method has been developed for the analysis of 4,4'-diaminodiphenylmethane (DDM), 3-ethyl DDM (EDDM), and 3,3'-diethyl DDM (DEDDM) in urine. The method has been applied to the analysis of urine samples from workers exposed to a mixture of all three compounds, and the analysis has shown that EDDM and DEDDM are excreted in urine. We have also shown that there are two classes of conjugates present in urine. EDDM and DEDDM are excreted as heat labile conjugates, while DDM and EDDM are excreted, at least in part, as heat stable but alkaline hydrolyzable conjugates. It is proposed that the method described here could be used for biological monitoring of workers exposed to mixtures of DDM, EDDM, and DEDDM.