Autophagy induced by taurolidine protects against polymicrobial sepsis by promoting both host resistance and disease tolerance.

Sepsis, septic shock, and their sequelae are the leading causes of death in intensive care units, with limited therapeutic options. Disease resistance and tolerance are two evolutionarily conserved yet distinct defense strategies that protect the host against microbial infection. Here, we report that taurolidine administered at 6 h before septic challenge led to strong protection against polymicrobial sepsis by promoting both host resistance and disease tolerance characterized by accelerated bacterial clearance, ameliorated organ damage, and diminished vascular and gut permeability. Notably, taurolidine administered at 6 h after septic challenge also rescued mice from sepsis-associated lethality by enhancing disease tolerance to tissue and organ injury. Importantly, this in vivo protection afforded by taurolidine depends on an intact autophagy pathway, as taurolidine protected wild-type mice but was unable to rescue autophagy-deficient mice from microbial sepsis. In vitro, taurolidine induced light chain 3-associated phagocytosis in innate phagocytes and autophagy in vascular endothelium and gut epithelium, resulting in augmented bactericidal activity and enhanced cellular tolerance to endotoxin-induced damage in these cells. These results illustrate that taurolidine-induced autophagy augments both host resistance and disease tolerance to bacterial infection, thereby conferring protection against microbial sepsis.

Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

A Randomized Clinical Trial Evaluating the Efficacy and Quality of Life of Antibiotic-only Treatment of Acute Uncomplicated Appendicitis: Results of the COMMA Trial.

OBJECTIVE: Evaluate the efficacy and quality of life associated with conservative treatment of acute uncomplicated appendicitis. SUMMARY BACKGROUND DATA: Conservative management with antibiotics only has emerged as a potential treatment option for acute uncomplicated appendicitis. However the reported failure rates are highly variable and there is a paucity of data in relation to quality of life. METHODS: Symptomatic patients with radiological evidence of acute, uncomplicated appendicitis were randomized to either intravenous antibiotics only or undergo appendectomy. RESULTS: One hundred eighty-six patients underwent randomization. In the antibiotic-only group, 23 patients (25.3%) experienced a recurrence within 1 year following randomization. There was a significantly better EQ-VAS quality of life score in the surgery group compared with the antibiotic-only group at 3 months (94.3 vs 91.0, P < 0.001) and 12 months postintervention (94.5 vs 90.4, P < 0.001). The EQ-5D-3L quality-of-life score was significantly higher in the surgery group indicating a better quality of life (0.976 vs 0.888, P < 0.001). The accumulated 12-month sickness days was 3.6 days shorter for the antibiotics only group (5.3 vs 8.9 days; P < 0.01). The mean length of stay in both groups was not significantly different (2.3 vs 2.8 days, P = 0.13). The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs €3,077, P < 0.001). CONCLUSIONS: Patients with acute, uncomplicated appendicitis treated with antibiotics only experience high recurrence rates and an inferior quality of life. Surgery should remain the mainstay of treatment for this commonly encountered acute surgical condition.

Screening for second malignancies in mycosis fungoides: non-Hodgkin lymphoma, Hodgkin lymphoma, lung cancer, bladder cancer and melanoma.

BACKGROUND: Patients with mycosis fungoides (MF) are at increased risk of developing non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), lung cancer, bladder cancer and melanoma. The characteristics of patients developing these malignancies have not been specifically delineated. In addition, there are no established guidelines for screening MF patients for second malignancies. MATERIALS/METHODS: We identified 742 patients with MF who developed second malignancies in the Surveillance Epidemiology and End Result-18 database. RESULTS: The majority of second malignancy patients were white and male, mean age 55-67 years at diagnosis of MF, and mean age 61-72 years at diagnosis of second malignancy. The majority of patients diagnosed with second malignancies had early stage MF. MF patients with NHL, lung cancer, and bladder cancer tended to be diagnosed at earlier stages of the second malignancy than patients without MF and demonstrated better 5-year overall survival. There was no improvement in stage at diagnosis or survival for MF patients who were diagnosed with melanoma compared to patients without MF. CONCLUSIONS: Improvements in survival in MF/NHL, MF/lung cancer and MF/bladder cancer patients may reflect differences in disease biology secondary to having MF or the importance of increased contact with the healthcare system. MF/melanoma data suggest that patients require regular pigmented-lesion-focused skin examinations. Tools for screening include regular lymph node examinations, pigmented-lesion-focused examinations and detailed review of systems questions. Smoking cessation counseling is key intervention in this population, as is ensuring that all age- and sex-specific cancer screenings are up-to-date (e.g. lung cancer screening, mammography, and colonoscopy). The utility of regular imaging for second malignancy screening and lab testing such as routine urinalysis requires additional study and expert consensus.

Mycosis fungoides: developments in incidence, treatment and survival.

BACKGROUND: Prior studies have demonstrated improved disease-specific survival of mycosis fungoides (MF) patients over the last 50 years. OBJECTIVE: To analyse patterns of survival and incidence from 1973 to 2016 and determine whether apparent improvements in MF-specific survival are due to lead-time bias rather than improvements in treatment. METHODS: We performed an analysis of 10 155 patients diagnosed with MF from 1973 to 2016 in the United States cancer registries of SEER-18. We also performed a literature review of papers including stage data for unselected populations of MF patients prior to 2000. RESULTS: Incidence of MF increased from 3.0 per million person-years in the 1970s to 5.9 in the 2010s. For all cohorts, non-Hodgkin lymphoma (including MF) was the leading cause of death. Survival analysis demonstrated marked improvement in disease-specific and overall survival from the 1970s to 2010s. Based on systematic review of the literature, 32%-73% of patients diagnosed prior to 2000 were diagnosed with early-stage disease, as opposed to 81% of patients in the SEER 2000-2016 cohort (P < 0.035 for all cohorts). CONCLUSIONS: Although there have been improvements in MF-related survival over the last 50 years, these may reflect improvements in our ability to diagnose early-stage disease rather than improved treatment.

Nuclear singlet relaxation by scalar relaxation of the second kind in the slow-fluctuation regime.

The singlet state of nuclear spin-1/2 pairs is protected against many common relaxation mechanisms. Singlet order, which is defined as the population difference between the nuclear singlet and triplet states, usually decays more slowly than the nuclear magnetization. Nevertheless, some decay mechanisms for nuclear singlet order persist. One such mechanism is called scalar relaxation of the second kind (SR2K) and involves the relaxation of additional nuclei ("third spins") which have scalar couplings to the spin-1/2 pair. This mechanism requires a difference between the couplings of at least one third spin with the two members of the spin-1/2 pair, and depends on the longitudinal relaxation time of the third spin. The SR2K mechanism of nuclear singlet relaxation has previously been examined in the case where the relaxation rate of the additional spins is on the time scale of the nuclear Larmor frequency. In this paper, we consider a different regime, in which the longitudinal relaxation of the third spins is on a similar time scale to the J-coupling between the members of the spin pair. This regime is often encountered when the spin-1/2 pair has scalar couplings to nearby deuterium nuclei. We show that the SR2K mechanism may be suppressed in this regime by applying a radiofrequency field which is resonant either with the members of the spin pair, or with the third spins. These phenomena are analyzed theoretically and by numerical simulations, and demonstrated experimentally on a diester of [13C2, 2H2]-labeled fumarate in solution.

Longer small bowel segments are resected in emergency surgery for ileocaecal Crohn's disease with a higher ileostomy and complication rate.

BACKGROUND: Repeated intestinal resections may have disabling consequences in patients with Crohn's disease even in the absence of short bowel syndrome. Our aim was to evaluate the length of resected small bowel in patients undergoing elective and emergency surgery for ileocolic Crohn's disease. METHODS: A prospective observational study was conducted on patients undergoing surgery for ileocolonic Crohn's disease in a single colorectal centre from May 2010 to April 2018. The following patients were included: (1) patients with first presentation of ileocaecal Crohn's disease undergoing elective surgery; (2) patients with ileocaecal Crohn's disease undergoing emergency surgery; (3) patients with recurrent Crohn's disease of the distal ileum undergoing elective surgery. The primary outcomes were length of resected small bowel and the ileostomy rate. Operating time, complications and readmissions within 30 days were the secondary outcomes. RESULTS: One hundred and sixty-eight patients were included: 87 patients in the elective primary surgery group, 50 patients in the emergency surgery group and 31 in the elective redo surgery group. Eleven patients (22%) in the emergency surgery group had an ileostomy compared to 10 (11.5%) in the elective surgery group (p < 0.0001). In the emergency surgery group the median length of the resected small bowel was 10 cm longer than into the group having elective surgery for primary Crohn's disease. CONCLUSIONS: Patients undergoing emergency surgery for Crohn's disease have a higher rate of stoma formation and 30-day complications. Laparoscopic surgery in the emergency setting has a higher conversion rate and involves resection of longer segments of small bowel.

Recent advances in ruthenium-based olefin metathesis.

Ruthenium-based olefin metathesis catalysts, known for their functional group tolerance and broad applicability in organic synthesis and polymer science, continue to evolve as an enabling technology in these areas. A discussion of recent mechanistic investigations is followed by an overview of selected applications.

RandomiSed clinical trial assessing Use of an anti-inflammatoRy aGent in attenUating peri-operatiVe inflAmmatioN in non-meTastatic colon cancer - the S.U.R.G.U.V.A.N.T. trial.

BACKGROUND: Peri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised. METHODS: We conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence. RESULTS: A total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo (p = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group (p = 0.27). Surgical site infection was reduced in the Taurolidine treated group (p = 0.09). CONCLUSION: Peri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer. TRIAL REGISTRATION: The trial was registered with EudraCT (year = 2008, registration number = 005570-12 ) and ISRCTN (year = 2008, registration number = 77,829,558 ).

Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms.

BACKGROUND: Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities. METHOD: Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined. RESULTS: HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior. CONCLUSIONS: Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.

Clinical assessment to determine the risk of bowel cancer using Symptoms, Age, Mass and Iron deficiency anaemia (SAMI).

BACKGROUND: The aim of this study was to identify characteristics with independent predictive value for bowel cancer for use in the clinical assessment of patients attending colorectal outpatient clinics. METHODS: This was a 22-year (1986-2007) retrospective cohort analysis of data collected prospectively from patients who attended colorectal surgical outpatient clinics in Portsmouth. The data set was split randomly into two groups of patients to generate and validate a predictive model. Multivariable logistic regression was used to create and validate a system to predict outcome. Receiver operating characteristic (ROC) curves and Hosmer-Lemeshow test were used to evaluate the model's predictive capability. The likelihood of bowel cancer was expressed as the odds ratio (OR). RESULTS: Data from 29 005 patients were analysed. Discrimination of the model for bowel cancer was high in the development (C-statistic 0·87, 95 per cent c.i. 0·85 to 0·88) and validation (C-statistic 0·86, 0·84 to 0·87) groups. The most important co-variables in the final model were: age (OR 3·17-27·10), rectal (OR 31·48) or abdominal (OR 1·83-8·45) mass, iron deficiency anaemia (IDA) (OR 4·42-8·38), rectal bleeding and change in bowel habit in combination (OR 5·37), change in bowel habit without rectal bleeding, with or without abdominal pain (OR 2·12-2·52), and rectal bleeding with no perianal symptoms and without change in bowel habit (OR 2·91). Some 91·5 per cent of bowel cancers presented with these characteristics, 40·4 per cent with a mass and/or IDA. In patients with at least one of these characteristics the overall risk of having cancer was 10·0 (range 6·5-50·4) per cent, compared with 1·1 (0·3-2·3) per cent in patients without them. CONCLUSION: A clinical assessment that systematically identifies or excludes four symptom-age combinations, a mass and IDA (SAMI) stratifies patients as having a low and higher risk of having bowel cancer. This could improve patient selection for referral and investigation.

Comparison of QT-interval and variability index methodologies in individuals with spinal cord injury.

STUDY DESIGN: Within-group comparison. OBJECTIVES: Individuals with spinal cord injury (SCI) demonstrate an elevated risk for cardiac arrhythmias as indicated by an elevated QT-variability index (QTVI). The methodology measuring the QTVI, however, is not standardized, and therefore the purpose of this investigation is to determine whether the threshold and tangent methods of QT-interval measurement, as well as the electrocardiographic (ECG) epoch duration, influence the QTVI in individuals with SCI. SETTING: Ontario, Canada. METHODS: Ten minutes of resting ECG data were collected and analyzed from 14 individuals with SCI (C2-L3; ASIA Impairment Scale (AIS) A-D; 11.5±9.4 years post injury). The QTVI was analyzed via the threshold and tangent methods of QT-interval measurement, as well as from 1-, 5- and 10-min ECG epochs. RESULTS: The threshold method produced significantly higher QTVI values compared with the tangent method. The QTVI from a 1-min epoch was significantly higher compared with that from 5- and 10-min epochs. The QTVI values acquired from the threshold method were shown to have higher reproducibility compared with those from the tangent method. There were no differences in QTVI values between participants with lesions above and below T1, as shown by both methods of QT-interval measurement. CONCLUSION: The method of QT-interval measurement and the length of ECG epoch influence QTVI values in individuals with SCI. The methodology of QTVI analysis must be standardized in studies involving SCI individuals to reduce the variability accounted by methodological inconsistency.

The effect of blood volume and volume loading on left ventricular diastolic function in individuals with spinal cord injury.

STUDY DESIGN: Cohort Study (Prospective Observational Study). OBJECTIVES: The objectives of the study were (i) to examine left ventricular (LV) diastolic function at rest and during rapid saline infusion in those with spinal cord injury (SCI) and (ii) to determine the contribution of blood volume on the purported diastolic impairments in individuals with SCI. SETTINGS: St Catharines, ON, Canada. METHODS: Thirteen SCI (AIS:A-D; C4-T6; age: 41±8.5; 10 males, 3 females) and 12 able-bodied (AB) individuals (age: 40±8.5; 9 males, 3 females) without a history of cardiovascular disease participated in the study. LV structure and diastolic function were assessed via conventional echocardiography. The carbon monoxide rebreathe test was used to measure the blood volume. LV diastolic function was assessed once more following rapid saline infusion (dose: 15 ml kg-1; rate: 100 ml min-1). RESULTS: Compared with the AB group, individuals with SCI had a smaller LV internal diameter (SCI: 4.5±0.3 cm vs AB: 5.1±0.7 cm; P=0.01), lower blood volume (SCI: 3.9±0.6 l vs AB: 5.0±1.2 l; P=0.02) and end-diastolic volume (SCI: 97.2±29.4 ml vs AB: 128.6±38.3 ml; P=0.03). There were no between-group differences in baseline diastolic parameters; however, when LV internal diameter was adjusted for individuals with SCI demonstrated lower early to late transmitral velocity ratio (SCI: 1.9±0.5 vs AB: 2.2±0.7; P=0.03). There was no between-group difference in diastolic responses to the saline infusion, as both groups showed similar diastolic changes following volume loading. CONCLUSION: Individuals with SCI have preserved LV diastolic function despite having lower preload. Preserved diastolic function may be mediated by the cardiac atrophy that occurs following SCI. Individuals with SCI also demonstrate normal diastolic responses to increased volume loading, suggesting compliant ventricles.

The effect of purse-string approximation versus linear approximation of ileostomy reversal wounds on morbidity rates and patient satisfaction: the 'STOMA' trial.

BACKGROUND: Ileostomy reversal is associated with surgical site infection (SSI) rates as high as 37%. Recent literature suggests that employing a purse-string approximation (PSA) of the reversal wound reduces this rate of SSI. Thus we wished to perform a randomised controlled trial to compare SSI rates in purse-string versus linear closure (PLC) wounds following ileostomy reversal. METHODS: A randomised, controlled trial was conducted at University Hospital Limerick. Sixty-one patients undergoing ileostomy reversal were included. Thirty-four patients were randomised to PSA and 27 patients to linear closure. The primary endpoint was incidence of SSI and secondary endpoints measured were quality of life and satisfaction with cosmesis. Statistical analysis was performed on a per protocol basis using SPSS version 22.0. RESULTS: Three patients in the PSA group developed an SSI compared to 8 in the PLC group at 30 days (8 vs 30%, p = 0.03). The mean time to SSI diagnosis was faster in the PSA group (3 vs 12.3 days, p = 0.08). Patients who developed SSI experienced a longer mean length of stay (6.8 vs 11.4 days, p = 0.012). On multivariate analysis, PLC was the only predictive factor of SSI formation (p < 0.001). There was no difference in patient satisfaction between the two study groups (p = 0.14). CONCLUSIONS: PSA of wounds following ileostomy reversal significantly reduces SSI formation compared to linear approximation without any effect on patient satisfaction.

Translational neurocardiology: preclinical models and cardioneural integrative aspects.

Neuronal elements distributed throughout the cardiac nervous system, from the level of the insular cortex to the intrinsic cardiac nervous system, are in constant communication with one another to ensure that cardiac output matches the dynamic process of regional blood flow demand. Neural elements in their various 'levels' become differentially recruited in the transduction of sensory inputs arising from the heart, major vessels, other visceral organs and somatic structures to optimize neuronal coordination of regional cardiac function. This White Paper will review the relevant aspects of the structural and functional organization for autonomic control of the heart in normal conditions, how these systems remodel/adapt during cardiac disease, and finally how such knowledge can be leveraged in the evolving realm of autonomic regulation therapy for cardiac therapeutics.

Influence of complications following immediate breast reconstruction on breast cancer recurrence rates.

BACKGROUND: The rate of immediate breast reconstruction is rising. Postoperative infections are more frequent in patients who undergo reconstruction. The inflammatory response to a postoperative infection can increase the risk of tumour recurrence in other forms of cancer through the release of proinflammatory mediators. The aim of this study was to assess the relationship between complications and breast cancer recurrence in patients undergoing immediate reconstruction. METHODS: This was a review of a prospectively maintained database of all patients who had immediate breast reconstruction between 2004 and 2009 at Galway University Hospital, a tertiary breast cancer referral centre serving the west of Ireland. All patients had a minimum follow-up of 5 years. Outcomes assessed included the development of wound complications and breast cancer recurrence. The data were evaluated by univariable and multivariable Cox regression analysis. RESULTS: A total of 229 patients who underwent immediate reconstruction were identified. The overall 5-year recurrence-free survival rate was 85·6 per cent. Fifty-three patients (23·1 per cent) had wound complications, of whom 44 (19·2 per cent) developed a wound infection. There was a significantly greater risk of developing systemic recurrence among patients who experienced a postoperative wound complication compared with those without a complication (hazard ratio 4·94, 95 per cent c.i. 2·72 to 8·95; P < 0·001). This remained significant after adjusting for Nottingham Prognostic Index group in the multivariable analysis. The 5-year recurrence-free survival rate for patients who had a wound complication was 64 per cent, compared with 89·2 per cent in patients without a complication (P < 0·001). CONCLUSION: This study has demonstrated that wound complications after immediate breast reconstructive surgery have significant implications for patients with breast cancer. Strategies are required to minimize the risk of postoperative wound complications in patients with breast cancer undergoing immediate reconstruction.

A case-control study of risk factors for death from 2009 pandemic influenza A(H1N1): is American Indian racial status an independent risk factor?

Historically, American Indian/Alaska Native (AI/AN) populations have suffered excess morbidity and mortality from influenza. We investigated the risk factors for death from 2009 pandemic influenza A(H1N1) in persons residing in five states with substantial AI/AN populations. We conducted a case-control investigation using pandemic influenza fatalities from 2009 in Alaska, Arizona, New Mexico, Oklahoma and Wyoming. Controls were outpatients with influenza. We reviewed medical records and interviewed case proxies and controls. We used multiple imputation to predict missing data and multivariable conditional logistic regression to determine risk factors. We included 145 fatal cases and 236 controls; 22% of cases were AI/AN. Risk factors (P 45 years vs. <18 years], pre-existing medical conditions (mOR 7·1), smoking (mOR 3·0), delayed receipt of antivirals (mOR 6·5), and barriers to healthcare access (mOR 5·3). AI/AN race was not significantly associated with death. The increased influenza mortality in AI/AN individuals was due to factors other than racial status. Prevention of influenza deaths should focus on modifiable factors (smoking, early antiviral use, access to care) and identifying high-risk persons for immunization and prompt medical attention.

Identification of the optimal visual recording system in open abdominal surgery - a prospective observational study.

INTRODUCTION: Current methodologies used to record and render the surgeon's point of view in open operative surgery remain limited. Chief among these limitations is a failure to demonstrate, in high definition and magnification, the planar roadmap that surgeons utilise in colorectal surgery. The high magnification and high resolution views provided during laparoscopic surgery simultaneously capture the planar road map and surgeon's point of view. We developed an arm-mounted external laparoscope (exoscope) system and compared its performance against multiple standard recording modalities. METHODS: Following ethical approval and informed consent, open colorectal procedures were recorded using five separate methodologies. Each methodology was assessed and compared. RESULTS: Most of the methodologies utilised scored poorly at one if not more levels. The arm-mounted external laparoscope (exoscope) scored highest in rendering the surgeon's point of view while simultaneously achieving high resolution and high magnification rendition of operative field (p < .001). This methodology was tested in a number of operative contexts within which it reproducibly and consistently scored highly. CONCLUSIONS: The arm-mounted exoscope is the optimal means of rendering the surgeon's point of view of anatomic planes during open colorectal surgery.

Major postoperative complications following elective resection for colorectal cancer decrease long-term survival but not the time to recurrence.

AIM: The aim of the study was to determine the effect of major complications after colorectal cancer surgery on survival and time to recurrence. METHOD: Patients having a curative colorectal cancer resection and a follow-up of at least 3 years were identified from a prospective database. Major complications were defined as Clavien-Dindo Grades 3b or 4 and their impact on time to recurrence and mortality was analysed by univariate and multivariable analysis. Postoperative death within 30 days or during the initial hospitalization (Clavien-Dindo Grade 5) was a priori excluded. RESULTS: From 2003 to 2012, 868 colorectal cancer resections resulting in 63 (7%) major postoperative complications including deaths (Clavien-Dindo ≥ 3b) were identified. After exclusion of Grade 5 complications (postoperative or in-hospital deaths), 844 resections with 39 (5%) major complications remained for analysis. Median follow-up time was 5.7 years. Using the Kaplan-Meier method, the estimated crude 5-year overall survival probability was 78% (95% CI 75-81) in the group without and 65% (95% CI 51-83) in the group with major complications (P = 0.009, log-rank test). Major complications were a significant negative predictor for overall survival (hazard ratio 2.42, 95% CI 1.41-4.14) when adjusted for sex, age, American Society of Anesthesiologists grade, tumour site (colon vs rectum), R stage and tumour stage. However, in both univariate and multivariable analysis, major complications were not a significant predictor for time to recurrence (hazard ratio 1.29, 95% CI 0.56-2.99). CONCLUSION: Non-lethal major postoperative complications seem to have a negative long-term impact on survival but not on time to recurrence.