Current use of drains and management of seroma following mastectomy and axillary surgery: results of a United Kingdom national practice survey.

PURPOSE: Up to 40% of the 56,000 women diagnosed with breast cancer each year in the UK undergo mastectomy. Seroma formation following surgery is common, may delay wound healing, and be uncomfortable or delay the start of adjuvant treatment. Multiple strategies to reduce seroma formation include surgical drains, flap fixation and external compression exist but evidence to support best practice is lacking. We aimed to survey UK breast surgeons to determine current practice to inform the feasibility of undertaking a future trial. METHODS: An online survey was developed and circulated to UK breast surgeons via professional and trainee associations and social media to explore current attitudes to drain use and management of post-operative seroma. Simple descriptive statistics were used to summarise the results. RESULTS: The majority of surgeons (82/97, 85%) reported using drains either routinely (38, 39%) or in certain circumstances (44, 45%). Other methods for reducing seroma such as flap fixation were less commonly used. Wide variation was reported in the assessment and management of post-operative seromas. Over half (47/91, 52%) of respondents felt there was some uncertainty about drain use after mastectomy and axillary surgery and two-thirds (59/91, 65%) felt that a trial evaluating the use of drains vs no drains after simple breast cancer surgery was needed. CONCLUSIONS: There is a need for a large-scale UK-based RCT to determine if, when and in whom drains are necessary following mastectomy and axillary surgery. This work will inform the design and conduct of a future trial.

Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Acute impact of aerobic exercise on local cutaneous thermal hyperaemia.

Little is known about the acute changes in cutaneous microvascular function that occur in response to exercise, the accumulation of which may provide the basis for beneficial chronic cutaneous vascular adaptations. Therefore, we examined the effects of acute exercise on cutaneous thermal hyperaemia. Twelve healthy, recreationally active participants (11 male, 1 female) performed 30-minute cycling at 50 % (low-intensity exercise, LOW) or 75 % (high-intensity exercise, HIGH) maximum heart rate. Laser Doppler flowmetry (LDF) and rapid local skin heating were used to quantify cutaneous thermal hyperaemia before (PRE), immediately following (IMM) and 1-h (1HR) after exercise. Baseline, axon reflex peak, axon reflex nadir, plateau, maximum skin blood flow responses to rapid local heating (42 °C for 30-min followed by 44 °C for 15-min) at each stage were assessed and indexed as cutaneous vascular conductance [CVC = flux / mean arterial blood pressure (MAP), PU·mm Hg-1], and expressed as a percentage of maximum (%CVCmax). Exercise increased heart rate (HR), MAP and skin blood flow (all P < 0.001), and to a greater extent during HIGH (all P < 0.001). The axon reflex peak and nadir were increased immediately and 1-h after exercise (all comparisons P < 0.01 vs. PRE), which did not differ between intensities (peak: P = 0.34, axon reflex nadir: P = 0.91). The endothelium-dependent plateau response was slightly elevated after exercise (P = 0.06), with no effect of intensity (P = 0.58) nor any interaction effect (P = 0.55). CONCLUSION: Exercise increases cutaneous microvascular axonal responses to local heating for up to 1-h, suggesting an augmented sensory afferent function post-exercise. Acute exercise may only modestly affect endothelial function in cutaneous microcirculation.

Are physical performance and frailty assessments useful in targeting and improving access to adjuvant therapy in patients undergoing resection for pancreatic cancer?

BACKGROUND: Many patients fail to receive adjuvant chemotherapy following pancreatic cancer surgery. This study implemented a multimodal, multidisciplinary approach to improving recovery after pancreatoduodenectomy (the 'Fast Recovery' programme) and measured its impact on adjuvant chemotherapy uptake and nutritional decline. The predictive accuracies of a bundle of frailty and physical performance assessments, with respect to the recipient of adjuvant chemotherapy, were also evaluated. RESULTS: The N = 44 patients treated after the introduction of the 'Fast Recovery' programme were not found to have a significantly higher adjuvant chemotherapy uptake than the N = 409 treated before the pathway change (80.5 vs. 74.3%, p = 0.452), but did have a significantly lower average weight loss at six weeks post-operatively (mean: 4.3 vs. 6.9 kg, p = 0.013). Of the pre-operative frailty and physical performance assessments tested, the 6-min walk test was found to be the strongest predictor of the receipt of adjuvant chemotherapy (area under the ROC curve: 0.91, p = 0.001); all patients achieving distances ≥ 360 m went on to receive adjuvant chemotherapy, compared to 33% of those walking < 360 m. CONCLUSIONS: The multimodal 'Fast Recovery' programme was not found to significantly improve access to adjuvant chemotherapy, but did appear to have benefits in reducing nutritional decline. Pre-operative assessments were found to be useful in identifying patients at risk of non-receipt of adjuvant therapies, with markers of physical performance appearing to be the best predictors. As such, these markers could be useful in targeting pre- and post-habilitation measures, such as physiotherapy and improved dietetic support.

Outcomes of normothermic machine perfusion of liver grafts in repeat liver transplantation (NAPLES initiative).

BACKGROUND: Retransplantation candidates are disadvantaged owing to lack of good-quality liver grafts. Strategies that can facilitate transplantation of suboptimal grafts into retransplant candidates require investigation. The aim was to determine whether late liver retransplantation can be performed safely with suboptimal grafts, following normothermic machine perfusion. METHODS: A prospectively enrolled group of patients who required liver retransplantation received a suboptimal graft preserved via normothermic machine perfusion. This group was compared with both historical and contemporaneous cohorts of patient who received grafts preserved by cold storage. The primary outcome was 6-month graft and patient survival. RESULTS: The normothermic machine perfusion group comprised 26 patients. The historical (cold storage 1) and contemporaneous (cold storage 2) groups comprised 31 and 25 patients respectively. The 6-month graft survival rate did not differ between groups (cold storage 1, 27 of 31, cold storage 2, 22 of 25; normothermic machine perfusion, 22 of 26; P = 0.934). This was despite the normothermic machine perfusion group having significantly more steatotic grafts (8 of 31, 7 of 25, and 14 of 26 respectively; P = 0.006) and grafts previously declined by at least one other transplant centre (5 of 31, 9 of 25, and 21 of 26; P < 0.001). CONCLUSION: In liver retransplantation, normothermic machine perfusion can safely expand graft options without compromising short-term outcomes.

Liver transplantation is a life-saving procedure for many different diseases. In the UK, one in 10 patients awaiting transplant have had a previous liver transplant. These retransplant operations are complex, and the general belief is that a good-quality donor liver graft is required for best outcomes. However, there is a significant shortage of good-quality organs for liver transplantation, so many patients awaiting retransplantation spend longer on the waiting list. This study investigated whether a new technology, called normothermic machine perfusion, could be used to preserve lower-quality donor livers and have successful outcomes for patients undergoing retransplantation. Traditionally, good-quality livers are preserved in an ice box and the study compared the outcomes of these two different approaches. The aim was to prove that normothermic machine perfusion improves access to transplantation for this group of patients, without compromising outcomes. A group of patients who underwent retransplantation and received a lesser-quality liver preserved with normothermic machine perfusion was compared with two groups of patients who had received a transplant with traditional ice-box preservation. The complications, graft, and patient survival of the former group was compared with those in the latter two groups who underwent liver retransplantation with better-quality liver grafts. The rate of survival and adverse surgical outcomes were comparable between the groups of patients who received a liver preserved via traditional ice-box preservation, and those who received a lesser-quality liver preserved via normothermic machine perfusion. Normothermic machine perfusion can potentially expand the number of suitable donor livers available for retransplant candidates.

Impact of Frailty on Short-Term Outcomes After Laparoscopic and Open Hepatectomy.

BACKGROUND: Although laparoscopic hepatectomy (LH) is associated with improved short-term outcomes compared to open hepatectomy (OH), it is unknown whether frail patients also benefit from LH. The aim of this study was to evaluate the impact of frailty on post-operative outcomes after LH and OH. PATIENTS AND METHODS: Consecutive patients who underwent LH and OH between January 2011 and December 2018 were identified from a prospective database. Frailty was assessed using the modified Frailty Index (mFI), with patients scoring mFI ≥ 1 deemed to be frail. RESULTS: Of 1826 patients, 34.7% (N = 634) were frail and 18.6% (N = 340) were elderly (≥ 75 years). Frail patients had significantly higher 90-day mortality (6.6% vs. 2.9%, p < 0.001) and post-operative complications (36.3% vs. 26.1%, p < 0.001) than those who were not frail, effects that were independent of patient age on multivariate analysis. For those undergoing minor resections, the benefits of LH vs. OH were similar for frail and non-frail patients. Length of hospital stay was 53% longer in OH (vs. LH) in frail patients, compared to 58% longer in the subgroup of non-frail patients. CONCLUSIONS: Frailty is independently associated with inferior post-operative outcomes in patients undergoing hepatectomy. However, the benefits of laparoscopic (compared to open) hepatectomy are similar for frail and non-frail patients. Frailty should not be a contraindication to laparoscopic minor hepatectomy in carefully selected patients.

Positive lifestyle behaviours and emotional health factors are associated with low back pain resilience.

PURPOSE: To evaluate the relationship between lifestyle behaviours, emotional health factors, and low back pain (LBP) resilience. METHODS: This retrospective longitudinal study utilised 1,065 twins with a recent history of LBP from the Washington State Twin Registry. A lifestyle behaviour score was built using variables of body mass index, physical activity engagement, sleep quality, smoking status, and alcohol consumption. An emotional health score was built using variables of the absence of depressed mood, perceived stress, and active coping. The main outcome was LBP resilience, assessed as recovery ("bouncing back"), and sustainability (maintaining high levels of function despite LBP). RESULTS: After adjusting for covariates, there was no relationship between the lifestyle behaviour score (OR 1.05, 95% CI 0.97-1.15, p = 0.218) and the emotional health score (OR 1.08, 95% CI 0.98-1.19, p = 0.142) with the likelihood of recovering from LBP. There was however, evidence of a positive association between the lifestyle behaviour score (ß 0.20, 95% CI 0.04-0.36, p = 0.013), the emotional health score (ß 0.22, 95% CI 0.00-0.43, p = 0.049), and greater levels of sustainability. These results were confirmed by a within-pair analysis (lifestyle behaviour score: ß 1.79, 95% CI 0.05-3.53, p = 0.043) and (emotional health score: ß 0.52, 95% CI 0.09-0.96, p = 0.021) adjusting for genetic and early shared environmental confounding. CONCLUSION: Findings from this study suggest that people who adopt optimal lifestyle behaviours and positive emotional factors are more likely to be resilient and maintain high levels of function despite suffering from LBP.

A qualitative exploration of the feasibility and acceptability of Meaning-Centered Psychotherapy for Cancer Caregivers.

OBJECTIVE: Caregivers of patients with cancer are at significant risk for existential distress. Such distress negatively impacts caregivers' quality of life and capacity to serve in their role as healthcare proxies, and ultimately, contributes to poor bereavement outcomes. Our team developed Meaning-Centered Psychotherapy for Cancer Caregivers (MCP-C), the first targeted psychosocial intervention that directly addresses existential distress in caregivers. METHOD: Nine caregivers of patients with glioblastoma multiforme (GBM) enrolled in a pilot randomized controlled trial evaluating the feasibility, acceptability, and effects of MCP-C, and completed in-depth interviews about their experience in the therapy. One focus group with three MCP-C interventionists was also completed. RESULTS: Four key themes emerged from interviews: (1) MCP-C validated caregivers' experience of caregiving; (2) MCP-C helped participants reframe their "caregiving identity" as a facet of their larger self-identity, by placing caregiving in the context of their life's journey; (3) MCP-C enabled caregivers to find ways to assert their agency through caregiving; and (4) the structure and sequence of sessions made MCP-C accessible and feasible. Feedback from interventionists highlighted several potential manual changes and overall ways in which MCP-C can help facilitate caregivers' openness to discussing death and engaging in advanced care planning discussions with the patient. SIGNIFICANCE OF RESULTS: The overarching goal of MCP-C is to allow caregivers to concurrently experience meaning and suffering; the intervention does not seek to deny the reality of challenges endured by caregivers, but instead to foster a connection to meaning and purpose alongside their suffering. Through in-depth interviews with caregivers and a focus group with MCP interventionists, we have refined and improved our MCP-C manual so that it can most effectively assist caregivers in experiencing meaning and purpose, despite inevitable suffering.

Gemcitabine-based adjuvant chemotherapy in subtypes of ampullary adenocarcinoma: international propensity score-matched cohort study.

BACKGROUND: Whether patients who undergo resection of ampullary adenocarcinoma have a survival benefit from adjuvant chemotherapy is currently unknown. The aim of this study was to compare survival between patients with and without adjuvant chemotherapy after resection of ampullary adenocarcinoma in a propensity score-matched analysis. METHODS: An international multicentre cohort study was conducted, including patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma between 2006 and 2017, in 13 centres in six countries. Propensity scores were used to match patients who received adjuvant chemotherapy with those who did not, in the entire cohort and in two subgroups (pancreatobiliary/mixed and intestinal subtypes). Survival was assessed using the Kaplan-Meier method and Cox regression analyses. RESULTS: Overall, 1163 patients underwent pancreatoduodenectomy for ampullary adenocarcinoma. After excluding 187 patients, median survival in the remaining 976 patients was 67 (95 per cent c.i. 56 to 78) months. A total of 520 patients (53·3 per cent) received adjuvant chemotherapy. In a propensity score-matched cohort (194 patients in each group), survival was better among patients who received adjuvant chemotherapy than in those who did not (median survival not reached versus 60 months respectively; P = 0·051). A survival benefit was seen in patients with the pancreatobiliary/mixed subtype; median survival was not reached in patients receiving adjuvant chemotherapy and 32 months in the group without chemotherapy (P = 0·020). Patients with the intestinal subtype did not show any survival benefit from adjuvant chemotherapy. CONCLUSION: Patients with resected ampullary adenocarcinoma may benefit from gemcitabine-based adjuvant chemotherapy, but this effect may be reserved for those with the pancreatobiliary and/or mixed subtype.

ANTECEDENTES: Actualmente se desconoce si la quimioterapia adyuvante ofrece un beneficio en la supervivencia de los pacientes que se someten a resección de un adenocarcinoma ampular. El objetivo de este estudio fue comparar la supervivencia mediante la concordancia estimada por emparejamiento por puntaje de propensión, entre pacientes con y sin quimioterapia adyuvante después de la resección de un adenocarcinoma ampular. MÉTODOS: Se realizó un estudio internacional de cohortes multicéntrico, que incluyó a los pacientes que se sometieron a una duodenopancreatectomía por adenocarcinoma ampular (2006-2017) en 13 centros de seis países. Los puntajes de propensión se usaron para emparejar a los pacientes que recibieron quimioterapia adyuvante con los que no; tanto en la cohorte completa como en dos subgrupos (subtipo pancreaticobiliar / mixto e intestinal). La supervivencia se evaluó utilizando el método de Kaplan-Meier y las regresiones de Cox. RESULTADOS: En total, 1.163 pacientes fueron sometidos a una duodenopancreatectomía por adenocarcinoma ampular. Después de excluir a 179 pacientes, la mediana de supervivencia de los 976 pacientes restantes fue de 67 meses (i.c. del 95%, 56-78), de los cuales un total de 520 pacientes (53%) recibieron quimioterapia adyuvante. En una cohorte de emparejamiento por puntaje de propensión (194 versus 194 pacientes), la mediana de supervivencia fue mejor en los pacientes tratados con quimioterapia adyuvante en comparación con aquellos sin quimioterapia adyuvante (no se alcanzó la mediana de supervivencia versus 60 meses, respectivamente; P = 0,051). En el subtipo pancreaticobiliar/mixto se observó un beneficio en la supervivencia; no se alcanzó la mediana de supervivencia en pacientes que recibieron quimioterapia adyuvante versus 32 meses en el grupo sin quimioterapia, P = 0,020. El subtipo intestinal no mostró beneficio en la supervivencia de la quimioterapia adyuvante. CONCLUSIÓN: Los pacientes con adenocarcinoma ampular resecado pueden beneficiarse de la quimioterapia adyuvante basada en gemcitabina, pero este efecto podría reservarse para aquellos pacientes con subtipo de tumor pancreaticobiliar y/o mixto.

Enzyme replacement improves survival among patients with pancreatic cancer: Results of a population based study.

BACKGROUND: Pancreatic exocrine insufficiency (PEI) and malnutrition are prevalent among patients with pancreatic adenocarcinoma. Pancreatic enzyme replacement therapy (PERT) can correct PEI but its use among patients with pancreatic cancer is unclear as are effects upon survival. This population-based study sought to address these issues METHODS: Subjects with pancreatic adenocarcinoma were identified from the UK Clinical Practice Research Datalink (CPRD). Propensity score matching generated matched pairs of subjects who did and did not receive PERT. Progression to all-cause mortality was compared using parametric survival models that included a range of relevant co-variables RESULTS: PERT use among the whole cohort (987/4554) was 21.7%. Some 1614 subjects generated 807 matched pairs. This resulted in a total, censored follow-up period of 1643 years. There were 1403 deaths in total, representing unadjusted mortality rates of 748 and 994 deaths per 1000 person-years for PERT-treated cases and their matched non-PERT-treated controls, respectively. With reference to the observed survival in pancreatic adenocarcinoma patients, adjusted median survival time was 262% greater in PERT-treated cases (survival time ratio (STR) = 2.62, 95% CI 2.27-3.02) when compared with matched, non-PERT-treated controls. Survival remained significantly greater among subjects receiving PERT regardless of the studied subgroup with respect to use of surgery or chemotherapy CONCLUSIONS: This population based study observes that the majority of patients with pancreatic adenocarcinoma do not receive PERT. PERT is associated with increased survival among patients with pancreatic adenocarcinoma suggesting a lack of clinical awareness and potential benefit of addressing malnutrition among these patients.

Risk factors for subclinical hypocalcaemia, and associations between subclinical hypocalcaemia and reproductive performance, in pasture-based dairy herds in New Zealand.

AIMS To estimate the herd-level prevalence of subclinical hypocalcaemia within 3 days of calving, to determine cow and herd-level risk factors for this condition, and associations with reproductive performance, in pasture-based cows in New Zealand. METHODS Between 10 and 15 clinically healthy cows ≥3-years-old (n=1,051) were enrolled from 76 spring-calving dairy herds. Blood samples were collected from all cows on 1 or 2 days within 3 days of calving, and assayed for total concentrations of Ca in serum. Subclinical hypocalcaemia was defined as concentrations of Ca in serum ≤2.14 mmol/L, and herd-level prevalence was the percentage of sampled cows with subclinical hypocalcaemia. Breeding and pregnancy diagnosis data were obtained for each cow to calculate reproductive outcomes. Herd-level data about management practices were collected from farmers at enrolment. Associations between cow-level variables, and reproductive outcomes, and subclinical hypocalcaemia were examined using multivariable logistic regression mixed models. Associations between herd-level variables and prevalence of subclinical hypocalcaemia were examined using a multivariable linear regression model. RESULTS Mean herd-level prevalence of subclinical hypocalcaemia was 52 (95% CI=49-55)%. Risk of subclinical hypocalcaemia at the cow-level was associated with an interaction between age of cow and interval from calving to sampling (p=0.03). Increasing age of cow was associated with increased risk of subclinical hypocalcaemia, and cows sampled on the day of calving had an increased risk compared with cows sampled 1 or 2 days after calving. Increased herd-level prevalence of subclinical hypocalcaemia was associated with feeding grass silage (p=0.06) or maize silage (p=0.004), and feeding increasing amounts of elemental Mg in the form of magnesium oxide (p=0.02). The mean farmer-reported herd-level prevalence of clinical hypocalcaemia was 2.9 (95% CI=2.1-3.8)%. Subclinical hypocalcaemia was not associated with any of the reproductive outcomes measured. CONCLUSIONS AND CLINICAL RELEVANCE There was a high prevalence of subclinical hypocalcaemia in the pasture-fed, spring-calving dairy herds sampled and a large between-herd variation in prevalence. Subclinical hypocalcaemia increased with increasing age, and declined with time postpartum. Herd-level prevalence was associated with feeding grass silage and maize silage to pre-calving cows and with increasing amounts of supplemented magnesium oxide. Subclinical hypocalcaemia was not associated with reproductive outcomes.

Effect of treatment with oral Ca boluses following calving on concentrations of Ca in serum in pasture-based dairy cows.

AIMS To assess the effect of the administration of two oral Ca boluses on concentrations of total Ca, ß-hydoxybutyrate (BHB) and non-esterified fatty acids (NEFA) in serum, and urine pH, in recently calved pasture-fed dairy cows. METHODS Friesian or Friesian cross Jersey cows from one dairy farm were blocked by age and randomly assigned to no treatment (control; n=14), or treatment (n=13) with two oral Ca boluses administered approximately 12 hours apart, with the first bolus being given within 14 hours of calving. Each bolus weighed 198 g and contained 43 g of Ca; 31 g of Ca from calcium chloride and 12 g of Ca from calcium sulfate. Cows were enrolled over three calendar days, and all cows were managed in one group during the 24-hour study period. Blood samples were collected at 0, 1, 2, 4, 8, 12, 13, 14, 16, 20 and 24 hours after the initial treatment. Serum from each time point was analysed for concentrations of total Ca, and from 0, 12, and 24 hours for NEFA and BHB. Urine was collected at 0, 12 and 24 hours for pH measurement and pH was categorised as <7 or ≥7. The effect of treatment on percentage change in concentrations of Ca in serum relative to 0 hours, and concentrations of NEFA, BHB and urine pH, was examined using multivariable repeated measures mixed models with cow as a random effect. RESULTS In the final multivariable model for percentage change in concentrations of Ca, there was an interaction between time and treatment (p=0.004), with the percentage increase being higher in treatment than control cows at 1, 2, 4, 8 and 13 hours. At 12 hours, 5/13 (41%) treated cows had a urine pH <7compared to 0/12 (0%) control cows (p<0.001), and at 24 hours 13/13 (100%) treated cows had urine pH <7 compared to 0/12 (0%) control cows (p<0.001). Over the 24-hour period, mean concentrations of NEFA or BHB in serum were similar in treated and control cows (p>0.3). CONCLUSIONS AND CLINICAL RELEVANCE Oral treatment with two Ca boluses increased concentrations of total Ca in serum and decreased urine pH in pasture-fed cows. This bolus has the potential to reduce the prevalence and duration of subclinical hypocalcaemia in recently calved cows.

Examination of inequivalent wetting on the crystal habit surfaces of RS-ibuprofen using grid-based molecular modelling.

Synthonic engineering tools, including grid-based searching molecular modelling, are applied to investigate the wetting interactions of the solute and four crystallisation solvents (ethanol, ethyl acetate, acetonitrile and toluene) with the {100}, {001} and {011} forms of RS-ibuprofen. The grid-based methods, in particular the construction of a crystal slab parallel to a given plane in a coordinate system with one axis perpendicular to the surface, are defined in detail. The interaction strengths and nature (dispersive, hydrogen bonding (H-bonding) or coulombic forces) are related to the crystal growth rates and morphologies. The solute is found to interact strongest with the capping {011}, then the side {001} and weakest with the top {100} habit surfaces. The solute interactions with the {100} and {001} surfaces are found to be almost solely dominated by dispersive force contributions, whilst the same with the {011} surfaces are found to have a greater contribution from H-bonding and coulombic forces. The increased surface rugosity, at the molecular level of the {011} surfaces, results in a favourable docking site in a surface 'valley', not present in the {100} and {001} surfaces. The H-bonding solvents ethanol, acetonitrile and ethyl acetate are found to strongly interact with the {011} surfaces and weakly with the {001} surfaces, with the {011} interactions having a much greater contribution from H-bonding and coulombic forces. The interaction energies of the apolar and aprotic solvent toluene, with the {011} and {001} surfaces, are found to be very close. Toluene is found having slightly stronger interactions with the {001} than the {011} surfaces, which are all dominated by dispersive interactions. The ratio of the average energy of the top 100 solvent interactions with the {001} surface divided by the average energy of the top 100 interactions with the {011} surface is compared to the ratio of the experimentally measured growth rates of the same forms. In general, the interaction energy ratio is found to have an inverse ratio with the growth rates, implying that the solvents which are calculated to interact strongly with a particular surface are impeding the growth of that surface and reducing the growth rate, in turn impacting upon the final morphology of the material.

Ninety day mortality following pancreatoduodenectomy in England: has the optimum centre volume been identified?

BACKGROUND: Mortality following pancreatoduodenectomy is related to centre volume although the optimal volume is not defined. METHODS: Patients undergoing PD between 2001 and 2016 were identified from UK national databases. The effects of patient variables, centre volume and time period upon 90 day mortality were studied. RESULTS: 90 day mortality (970/14,935, 6.5%) was related to advanced age, comorbidity, diagnosis, ethnicity, deprivation, centre volume and time period. Mortality rates fell markedly from 10.0% in 2001-4 to 4.1% in 2013-16. There was no difference in 90 day mortality between high (36 -60 PD per year) and very high volume (>60) centres. However, patients operated upon at very high volume centres were more elderly (66, 58 -73 vs 65, 56 -72; median, IQR; p = 0.006), deprived (38.7 vs 34.6%; p < 0.001) and co morbid (48.9 vs 46.1%; p = 0.027). CONCLUSION: Although a plateau in the centre volume and mortality relationship appears to have been demonstrated those patients treated at the highest volume centres were at higher risk of mortality. This data suggests therefore that to further understand outcomes from specialist centres characteristics of the patient population should be defined, not just centre volume.

CB2 receptors regulate natural killer cells that limit allergic airway inflammation in a murine model of asthma.

BACKGROUND: Allergic asthma is a chronic airway inflammatory disease involving the complementary actions of innate and adaptive immune responses. Endogenously generated cannabinoids acting via CB2 receptors play important roles in both homeostatic and inflammatory processes. However, the contribution of CB2-acting eicosanoids to the innate events preceding sensitization to the common house dust mite (HDM) allergen remains to be elucidated. We investigated the role of CB2 activation during allergen-induced pulmonary inflammation and natural killer (NK) cell effector function. METHODS: Lung mucosal responses in CB2-deficient (CB2-/- ) mice were examined and compared with wild-type (WT) littermates following intranasal exposure to HDM allergen. RESULTS: Mice lacking CB2 receptors exhibited elevated numbers of pulmonary NK cells yet were resistant to the induction of allergic inflammation exemplified by diminished airway eosinophilia, type 2 cytokine production and mucus secretion after allergen inhalation. This phenomenon was corroborated when WT mice were treated with a CB2-specific antagonist that caused a pronounced inhibition of HDM-induced airway inflammation and goblet cell hyperplasia. Unexpectedly, the preponderance of NK cells in the lungs of CB2-/- mice correlated with reduced numbers of group 2 innate lymphoid cells (ILC2s). Depletion of NK cells restored the allergen responsiveness in the lungs and was associated with elevated ILC2 numbers. CONCLUSIONS: Collectively, these results reveal that CB2 activation is crucial in regulating pulmonary NK cell function, and suggest that NK cells serve to limit ILC2 activation and subsequent allergic airway inflammation. CB2 inhibition may present an important target to modulate NK cell response during pulmonary inflammation.

Performance of the revised Atlanta and determinant-based classifications for severity in acute pancreatitis.

BACKGROUND: Severity classification systems aim to stratify patients with acute pancreatitis reliably into coherent risk groups. Recently, the Atlanta 1992 classification has been revised (Atlanta 2012) and a novel determinant-based classification (DBC) system developed. This study assessed the ability of the three systems to stratify disease severity among patients with acute pancreatitis. METHODS: This was an observational cohort study of patients with acute pancreatitis identified from an institutional database. Cohort characteristics, investigations, interventions and outcomes were identified. Systems were compared using receiver operating characteristic (ROC) analysis and Spearman's correlation coefficients. RESULTS: The in-hospital mortality rate was 6·6 per cent (15 of 228 patients). All of the outcomes considered correlated significantly with the three systems, with the exception of the need for surgery in Atlanta 1992. Atlanta 2012 and the DBC had higher area under the curve (AUC) values than Atlanta 1992 for all outcomes. The revised Atlanta and DBC systems both performed similarly with regard to ICU admission (AUC 0·927 and 0·917 respectively; both P < 0·001), need for percutaneous drainage (AUC 0·879 and 0·891; both P < 0·001), need for surgery (AUC 0·827 and 0·845; P = 0·006 and P = 0·004 respectively) and in-hospital mortality (0·955 and 0·931; both P < 0·001). However, the critical category in the DBC system identified patients with the most severe disease; seven of eight patients in this group died in hospital, compared with 15 of 34 with severe pancreatitis according to Atlanta 2012. CONCLUSION: The Atlanta 2012 and DBC perform equally well for classification of disease severity in acute pancreatitis. The addition of a critical category in the DBC identifies patients with the most severe disease.

Do not forget the boys - gender differences in children living in high HIV-affected communities in South Africa and Malawi in a longitudinal, community-based study.

Gender is an important factor in child development. Especially in sub-Saharan Africa, girls have often been shown to be less likely to access education compared to boys. The consequence of this has been that that programmes addressing child development are often aimed at girls in order to redress gender imbalances. This study examines the effect of gender on the development of children attending community-based organisations in high HIV-affected areas, and explores whether community-based organisation attendance was associated with any changes in gender differences over time. Baseline data from 989 children and 12-15 month follow from 854 (86% response rate) were used to examine gender differences in children from Malawi and South Africa. At baseline, where there were differences by gender, these tended to disadvantage boys. It was found that boys were significantly more often found to be subjected to violence. Boys showed worse performance at school and more behavioural problems than girls. These gender differences persisted from baseline to follow-up. At follow-up, boys self-reported significantly worse average quality of life than girls. Only harsh discipline differed by gender in progression over time: boys experienced a stronger reduction in harsh physical discipline than girls from baseline to follow-up. Since harsh discipline was associated with boys' worse educational outcomes and behavioural problems, our data cautiously suggests that gender differences could be reduced over time. In conclusion, our data suggests that, perhaps due to the narrow equity approach focusing on provision for girls, boys may be overlooked. As a result, there are some specific experiences where boys are generally worse off. These differences have distinct ramifications for the educational and emotional development of boys. A broader equity approach to child development might be warranted to ensure that the needs of both girls and boys are considered, and that boys are not overlooked.

The influence of solution environment on the nucleation kinetics and crystallisability of para-aminobenzoic acid.

The influence of solvent type on the solution thermodynamics, nucleation-kinetics and crystal growth of alpha para-aminobenzoic acid (PABA) crystallising from supersaturated ethanol, acetonitrile and water solutions, is examined using poly-thermal analysis of the metastable zone width. Application of a recently proposed model for analysis of crystallisation kinetics (J. Cryst. Growth, 2010, 312, 698-704) indicates a solvent and concentration dependence of the nucleation mechanism and key nucleation parameters for the alpha form of PABA. The mechanism of nucleation is found to change from instantaneous to progressive with decreasing concentration and also when changing the solvent from ethanol to acetonitrile to water. The dependence of the nucleation mechanism is correlated to the kinetic component of the nucleation rate through calculated values of instantaneously nucleated crystallites, which increase from 1.40 × 109 m-3 in ethanol to 1.08 × 1010 m-3 in acetonitrile to 2.58 × 1010 m-3 in water. This in combination with low calculated number concentrations of interfacial tension between 1.13 and 2.71 mJ m-2, supports the conclusion that the kinetic component of the nucleation rate is more limiting when crystallising PABA from ethanol solutions in comparison to water solutions. This finding is further supported by molecular dynamics simulations of the solvation free energy of PABA, which is found to be greatest in water, -42.4 kJ mol-1 and lowest in ethanol, -58.5 kJ mol-1.

Comparison of preoperative CT-based imaging parameters to predict postoperative pancreatic fistula.

AIM: To review all reported methods of preoperative computed tomography (CT) in one patient cohort and to identify which were the strongest to predict postoperative pancreatic fistula (POPF) after pancreatoduodenectomy. MATERIALS AND METHODS: Consecutive patients undergoing pancreatoduodenectomy were included if they had unenhanced CT images for review. Eighteen variables and two scores were tested. Receiver operator characteristics (ROC) were explored. RESULTS: POPF affected 26 of 107 patients (24.3%). Nine variables were significantly related to POPF with pancreatic duct width having the largest area under the ROC curve (AUROC; 0.808, p<0.001). An obese body habitus was associated with POPF with six of nine related variables using data from CT images associated with POPF; of these intra-abdominal wall thickness yielded the largest AUROC (0.713, p=0.001). This corresponded to the finding that body mass index (BMI) was related to POPF (AUROC 0.705, p=0.002). The largest AUROC of all was associated with one of the predictive scores (0.828, p<0.001). Substituting BMI for intra-abdominal wall thickness in this score yielded a non-significant increase to predict POPF (AUROC 0.840, p=0.676). None of the assessments of organ density (in Hounsfield Units) were associated with POPF. CONCLUSION: Data from preoperative CT imaging provides valuable information regarding a patient's risk of POPF. Obesity as assessed by CT images strongly relates to POPF, but the largest single risk factor for POPF is a narrow pancreatic duct.