Polymorphisms in the androgen receptor CAG repeat sequence are related to tumour stage but not to ERG or androgen receptor expression in Malaysian men with prostate cancer.

INTRODUCTION: Polymorphic expression of a CAG repeat sequence in the androgen receptor (AR) gene may influence the activity of the AR and the occurrence of prostate cancer and the TMPRSS2-ERG fusion event. Furthermore, this polymorphism may be responsible for the ethnic variation observed in prostate cancer occurrence and expression of the ERG oncogene. We investigate the expression of AR and ERG in the biopsies of Malaysian men with prostate cancer and in the same patients relate this to the length of the CAG repeat sequence in their AR gene. MATERIALS AND METHODS: From a PSA screening initiative, 161 men were shown to have elevated PSA levels in their blood and underwent prostatic tissue biopsy. DNA was extracted from the blood, and exon 1 of the AR gene amplified by PCR and sequenced. The number of CAG repeat sequences were counted and compared to the immunohistochemical expression of ERG and AR in the matched tumour biopsies. RESULTS: Of men with elevated PSA, 89 were diagnosed with prostate cancer, and 72 with benign prostatic hyperplasia (BPH). There was no significant difference in the length of the CAG repeat in men with prostate cancer and BPH. The CAG repeat length was not associated with; age, PSA or tumour grade, though a longer CAG repeat was associated with tumour stage. ERG and AR were expressed in 36% and 86% of the cancers, respectively. There was no significant association between CAG repeat length and ERG or AR expression. However, there was a significant inverse relationship between ERG and AR expression. In addition, a significantly great proportion of Indian men had ERG positive tumours, compared to men of Malay or Chinese descent. CONCLUSIONS: CAG repeat length is not associated with prostate cancer or expression of ERG or AR. However, ERG appears to be more common in the prostate cancers of Malaysian Indian men than in the prostate cancers of other Malaysian ethnicities and its expression in this study was inversely related to AR expression.

Prior fragility fracture and risk of incident ischaemic cardiovascular events: results from UK Biobank.

In the large UK Biobank population-based cohort, we found that amongst men, but not women, prior fragility fracture was associated with increased risk of admission with ischaemic heart disease. INTRODUCTION: We aimed to investigate the relationship between prior fracture and risk of incident ischaemic cardiovascular events in a UK population-based cohort. METHODS: UK Biobank is a large prospective cohort comprising 502,637 men and women aged 40-69 years, with detailed baseline assessment. History of fracture was self-reported, and details of hospital admissions for ischaemic heart disease (IHD) (ICD-10:I20-I25) were obtained through linkage to UK Hospital Episode Statistics. Cox proportional hazards models were used to investigate the prospective relationships between prior fracture and hospital admission for men and women, controlling for age, BMI, smoking, alcohol, educational level, physical activity, systolic blood pressure, calcium and vitamin D use, ankle spacing-width, heel BUA and HRT use (women). RESULTS: Amongst men, a fragility fracture (hip, spine, wrist or arm fracture resulting from a simple fall) within the previous 5 years was associated with a 35% increased risk of IHD admission (fully adjusted HR 1.35; 95%CI 1.00, 1.82; p = 0.047), with the relationship predominantly driven by wrist fractures. Associations with hospitalisation for angina in men were similar in age-adjusted models [HR1.54; 95%CI: 1.03, 2.30), p = 0.037], but did not remain statistical significant after full adjustment [HR 1.64; 95%CI: 0.88, 3.07); p = 0.121]. HRs for admission with angina were lower in women, and neither age- nor fully adjusted relationships attained statistical significance. CONCLUSIONS: Prior fragility fracture is an independent risk factor for incident ischaemic cardiovascular events in men. Further work may clarify whether this association is causal or represents shared risk factors, but these findings are likely to be of value in risk assessment of both osteoporosis and cardiovascular disease.

Heterogenous expression of ERG oncoprotein in Malaysian men with adenocarcinoma of the prostate.

INTRODUCTION: Prostate cancer is a heterogenous disease and the mechanisms that drive it to behave differently are not well understood. Tumour expression of the ERG oncogene occurs in the majority of patients with prostate cancer in Western studies. This is considered to be oncogenic as ERG acts as a transcription factor to regulate genes involved in tumour proliferation and invasion. In this study we investigated expression of ERG in Malaysian men with prostate cancer. METHODS: Tissues were collected from 80 patients with clinically detected prostate cancer and treated with radical prostatectomy. Cases were tested for ERG by immunohistochemistry using the mouse monoclonal antibody EP111. All blocks on 48 cases were tested in order to determine the extent of heterogeneity of ERG expression within individual cases. ERG expression was analysed in relation to patient age, ethnicity and tumour stage and grade. RESULTS: Forty-six percent of cases were ERG positive. There was no significant association between ERG and tumour grade or stage. Sixty-nine percent of Indian patients had ERG positive tumours; this was significantly higher (p=0.031) than for Chinese (40%) and Malay (44%) patients. Heterogeneity of ERG expression, in which both positive and negative clones were present, was seen in 35% of evaluated cases. Evaluation by tumour foci showed younger patients had more ERG positive tumour foci than older patients (p=0.01). Indian patients were more likely to have the majority of tumour foci with ERG staining positively, compared to either Chinese or Malay patients (P <0.01). CONCLUSION: In this study, tumour expression of ERG was more likely to occur in patients of Indian ethnicity.

Effects of arterial load variations on dynamic arterial elastance: an experimental study.

BACKGROUND.: Dynamic arterial elastance (Ea dyn ), the relationship between pulse pressure variation (PPV) and stroke volume variation (SVV), has been suggested as a functional assessment of arterial load. The aim of this study was to evaluate the impact of arterial load changes during acute pharmacological changes, fluid administration, and haemorrhage on Ea dyn . METHODS.: Eighteen anaesthetized, mechanically ventilated New Zealand rabbits were studied. Arterial load changes were induced by phenylephrine ( n =9) or nitroprusside ( n =9). Thereafter, animals received a fluid bolus (10 ml kg -1 ), followed by stepwise bleeding (blood loss: 15 ml kg -1 ). The influence of arterial load and cardiac variables on PPV, SVV, and Ea dyn was analysed using a linear mixed-effects model analysis. RESULTS.: After phenylephrine infusion, mean ( sd ) Ea dyn decreased from 0.89 (0.14) to 0.49 (0.12), P <0.001; whereas after administration of nitroprusside, Ea dyn increased from 0.80 (0.23) to 1.28 (0.21), P <0.0001. Overall, the fluid bolus decreased Ea dyn [from 0.89 (0.44) to 0.73 (0.35); P <0.01], and haemorrhage increased it [from 0.78 (0.23) to 0.95 (0.26), P =0.03]. Both PPV and SVV were associated with similar arterial factors (effective arterial elastance, arterial compliance, and resistance) and heart rate. Furthermore, PPV was also related to the acceleration and peak velocity of aortic blood flow. Both arterial and cardiac factors contributed to the evolution of Ea dyn throughout the experiment. CONCLUSIONS.: Acute modifications of arterial load induced significant changes on Ea dyn ; vasodilatation increased Ea dyn , whereas vasoconstriction decreased it. The Ea dyn was associated with both arterial load and cardiac factors, suggesting that Ea dyn should be more properly considered as a ventriculo-arterial coupling index.

Anaplastic lymphoma kinase (ALK) mutations in patients with adenocarcinoma of the lung.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major cause of cancer-related death. Approximately 2-16% of NSCLC patients with wild-type epidermal growth factor receptor (EGFR) harbour anaplastic lymphoma kinase (ALK) mutations. Both EGFR and ALK mutations occur most commonly in Asian patients with NSCLC. As targeted therapy is available for NSCLC patients with these mutations, it is important to establish reliable assays and testing strategies to identify those most likely to benefit from this therapy. MATERIALS AND METHODS: Patients diagnosed with adenocarcinoma of the lung between 2010 and 2014 were tested for EGFR mutations. Of these, 92 cases were identified as EGFR wild type and suitable candidates for ALK testing utilising immunohistochemistry and the rabbit monoclonal antibody D5F3. The reliability of the IHC was confirmed by validating the results against those achieved by fluorescence in situ hybridisation (FISH) to detect ALK gene rearrangements. RESULTS: Twelve (13%) cases were positive for ALK expression using immunohistochemistry. Of the 18 evaluable cases tested by FISH, there was 100% agreement with respect to ALK rearrangement/ALK expression between the assays, with 11 cases ALK negative and 7 cases ALK positive by both assays. ALK tumour expression was significantly more common in female compared to male patients (29.6% vs. 6.2%, P < 0.001), detected exclusively in patients that had never smoked (P < 0.001) and more frequently in metastases (22.7%) than in primary tumours (10%) (P = 0.047). CONCLUSIONS: Detection of ALK expression by IHC is reliable and the most practical way of identifying NSCLC patients likely to benefit from crizotinib treatment.

Evaluation of clinical practice in perioperative patient blood management.

BACKGROUND: Several guidelines have been published to facilitate implementation of patient blood management (PBM). This study was performed to evaluate clinical practices in PBM. METHODS: An online survey based on the guidelines for the management of severe perioperative bleeding from the European Society of Anaesthesiology (ESA) was conducted among ESA members. We assessed characteristic data of participating physicians, preoperative assessment of bleeding risk and anaemia, intraoperative transfusion practices, specific pharmacologic treatment of significant bleeding, and clinical use of PBM algorithms. Data distributions for five European regions and the workplace and experience of physicians were analysed using a χ2 test. RESULTS: We received 706 fully completed surveys from physicians in 57 countries. Most (99%) respondents were anaesthetists or intensive care physicians, and 68% worked at university or university-affiliated hospitals. A standardised bleeding history before surgery is routinely obtained by 48% of physicians. When bleeding history is negative, 55% of physicians routinely order preoperative coagulation testing. Only 24% of physicians timely assess patients at risk of bleeding during surgery for anaemia before elective surgery. When anaemia is diagnosed, 38% of physicians routinely investigate its cause. The rate of routinely performed targeted haemostatic interventions with fibrinogen, vitamin K or prothrombin complex, and tranexamic acid was 60%, 52%, and 54%, respectively. Algorithms to guide PBM are used by 62% of physicians. Results varied between geographic regions. CONCLUSIONS: Major deficits exist in the use of recommended PBM among anaesthetists, indicating an opportunity to improve clinical standards.

Preoperative abnormalities in serum sodium concentrations are associated with higher in-hospital mortality in patients undergoing major surgery.

BACKGROUND: Abnormal serum sodium concentrations are common in patients presenting for surgery. It remains unclear whether these abnormalities are independent risk factors for postoperative mortality. METHODS: This is a secondary analysis of the European Surgical Outcome Study (EuSOS) that provided data describing 46 539 patients undergoing inpatient non-cardiac surgery. Patients were included in this study if they had a recorded value of preoperative serum sodium within the 28 days immediately before surgery. Data describing preoperative risk factors and serum sodium concentrations were analysed to investigate the relationship with in-hospital mortality using univariate and multivariate logistic regression techniques. RESULTS: Of 35 816 (77.0%) patients from the EuSOS database, 21 943 (61.3%) had normal values of serum sodium (138-142 mmol litre(-1)) before surgery, 8538 (23.8%) had hyponatraemia (serum sodium ≤137 mmol litre(-1)) and 5335 (14.9%) had hypernatraemia (serum sodium ≥143 mmol litre(-1)). After adjustment for potential confounding factors, moderate to severe hypernatraemia (serum sodium concentration ≥150 mmol litre(-1)) was independently associated with mortality [odds ratio 3.4 (95% confidence interval 2.0-6.0), P<0.0001]. Hyponatraemia was not associated with mortality. CONCLUSIONS: Preoperative abnormalities in serum sodium concentrations are common, and hypernatraemia is associated with increased mortality after surgery. Abnormalities of serum sodium concentration may be an important biomarker of perioperative risk resulting from co-morbid disease.

The role of heat shock proteins and glucose regulated proteins in cancer.

Heat shock proteins (HSPs) are a family of evolutionary conserved proteins that work as molecular chaperones for cellular proteins essential for cell viability and growth as well as having numerous cyto-protective roles. They are sub-categorised based on their molecular weights; amongst which some of the most extensively studied are the HSP90 and HSP70 families. Important members of these two families; Heat shock proteins 70 and heat shock proteins 90 (Hsp70/90), are the glucose regulated proteins (GRP). These stress-inducible chaperones possess distinct roles from that of the other HSPs, residing mostly in the endoplasmic reticulum and mitochondria, but they can also be translocated to other cellular locations. Their ability in adapting to stress conditions in the tumour microenvironment suggests novel functions in cancer. GRPs have been implicated in many crucial steps of carcinogenesis to include stabilization of oncogenic proteins, induction of tumour angiogenesis, inhibition of apoptosis and replicative senescence, and promotion of invasion and metastasis.

Point prevalence of surgical checklist use in Europe: relationship with hospital mortality.

BACKGROUND: The prevalence of use of the World Health Organization surgical checklist is unknown. The clinical effectiveness of this intervention in improving postoperative outcomes is debated. METHODS: We undertook a retrospective analysis of data describing surgical checklist use from a 7 day cohort study of surgical outcomes in 28 European nations (European Surgical Outcomes Study, EuSOS). The analysis included hospitals recruiting >10 patients and excluding outlier hospitals above the 95th centile for mortality. Multivariate logistic regression and three-level hierarchical generalized mixed models were constructed to explore the relationship between surgical checklist use and hospital mortality. Findings are presented as crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: A total of 45 591 patients from 426 hospitals were included in the analysis. A surgical checklist was used in 67.5% patients, with marked variation across countries (0-99.6% of patients). Surgical checklist exposure was associated with lower crude hospital mortality (OR 0.84, CI 0.75-0.94; P=0.002). This effect remained after adjustment for baseline risk factors in a multivariate model (adjusted OR 0.81, CI 0.70-0.94; P<0.005) and strengthened after adjusting for variations within countries and hospitals in a three-level generalized mixed model (adjusted OR 0.71, CI 0.58-0.85; P<0.001). CONCLUSIONS: The use of surgical checklists varies across European nations. Reported use of a checklist was associated with lower mortality. This observation may represent a protective effect of the surgical checklist itself, or alternatively, may be an indirect indicator of the quality of perioperative care. CLINICAL TRIAL REGISTRATION: The European Surgical Outcomes Study is registered with ClinicalTrials.gov, number NCT01203605.

Cardiac complications associated with goal-directed therapy in high-risk surgical patients: a meta-analysis.

Patients with limited cardiopulmonary reserve are at risk of mortality and morbidity after major surgery. Augmentation of oxygen delivery index (DO2I) with i.v. fluids and inotropes (goal-directed therapy, GDT) has been shown to reduce postoperative mortality and morbidity in high-risk patients. Concerns regarding cardiac complications associated with fluid challenges and inotropes may prevent clinicians from performing GDT in patients who need it most. We hypothesized that GDT is not associated with an increased risk of cardiac complications in high-risk, non-cardiac surgical patients. We performed a systematic search of Medline, Embase, and CENTRAL databases for randomized controlled trials (RCTs) of GDT in high-risk surgical patients. Studies including cardiac surgery, trauma, and paediatric surgery were excluded. We reviewed the rates of all cardiac complications, arrhythmias, myocardial ischaemia, and acute pulmonary oedema. Meta-analyses were performed using RevMan software. Data are presented as odds ratios (ORs), [95% confidence intervals (CIs)], and P-values. Twenty-two RCTs including 2129 patients reported cardiac complications. GDT was associated with a reduction in total cardiovascular (CVS) complications [OR=0.54, (0.38-0.76), P=0.0005] and arrhythmias [OR=0.54, (0.35-0.85), P=0.007]. GDT was not associated with an increase in acute pulmonary oedema [OR=0.69, (0.43-1.10), P=0.12] or myocardial ischaemia [OR=0.70, (0.38-1.28), P=0.25]. Subgroup analysis revealed the benefit is most pronounced in patients receiving fluid and inotrope therapy to achieve a supranormal DO2I, with the use of minimally invasive cardiac output monitors. Treatment of high-risk surgical patients GDT is not associated with an increased risk of cardiac complications; GDT with fluids and inotropes to optimize DO2I during early GDT reduces postoperative CVS complications.

Preoperative anaemia is associated with poor clinical outcome in non-cardiac surgery patients.

BACKGROUND: Retrospective studies suggest that preoperative anaemia is associated with poor outcomes after surgery. The objective of this study was to describe mortality rates and patterns of intensive care resource use for patients with anaemia undergoing non-cardiac and non-neurological in-patient surgery. METHODS: We performed a secondary analysis of a large prospective study describing perioperative care and survival in 28 European nations. Patients at least 16 yr old undergoing in-patient surgery during a 7 day period were included in the study. Data were collected for in-hospital mortality, duration of hospital stay, admission to intensive care, and intensive care resource use. Multivariable logistic regression analysis was performed to understand the effects of preoperative haemoglobin (Hb) levels on in-hospital mortality. RESULTS: We included 39 309 patients in the analysis. Preoperative anaemia had a high prevalence in both men and women (31.1% and 26.5%, respectively). Multivariate analysis showed that patients with severe [odds ratio 2.82 (95% confidence interval 2.06-3.85)] or moderate [1.99 (1.67-2.37)] anaemia had higher in-hospital mortality than those with normal preoperative Hb concentrations. Furthermore, hospital length of stay (P<0.001) and postoperative admission to intensive care (P<0.001) were greater in patients with anaemia than in those with normal Hb concentrations. CONCLUSIONS: Anaemia is common among non-cardiac and non-neurological surgical patients, and is associated with poor clinical outcome and increased healthcare resource use. CLINICAL TRIAL REGISTRATION: NCT01203605 (ClinicalTrials.gov).

Triple negative breast cancer: the role of metabolic pathways.

The incidence of breast cancer in Malaysia and other Asian countries is on the increase, reflecting lifestyle changes some of which are known risk factors for the development of breast cancer. Most breast cancers are amenable to adjuvant therapies that target hormone receptors or HER2 receptors on the surface of the cancer cells and bring about significant improvement in survival. However, approximately 17% of Malaysian women with breast cancer, present with tumours that are devoid of these receptors and are consequently termed 'triple negative' breast cancers. These triple negative breast cancers typically occur in women of a younger age than receptor positive cancers, are predominantly of high grade tumours and the prognosis is usually poor. There is therefore a pressing need to understand the biological pathways that drive these tumours, in order that effective strategies are developed to treat these aggressive tumours. With the increasing affluence of developing countries, obesity and Type II Diabetes are also on the rise. These diseases are associated with an increased risk of developing a range of cancers including those of the breast. In particular, the metabolic syndrome has been shown to be associated with triple negative breast cancer. This article reviews some of the metabolic pathways and biomarkers which have been shown to be aberrantly expressed in triple negative breast cancer and highlights some of the ongoing work in this area.

Goal-directed therapy in cardiac surgery: a systematic review and meta-analysis.

BACKGROUND: Perioperative mortality after cardiac surgery has decreased in recent years although postoperative morbidity is still significant. Although there is evidence that perioperative goal-directed haemodynamic therapy (GDT) may reduce surgical mortality and morbidity in non-cardiac surgical patients, the data are less clear after cardiac surgery. The objective of this review is to perform a meta-analysis on the effects of perioperative GDT on mortality, morbidity, and length of hospital stay in cardiac surgical patients. METHODS: We conducted a systematic review using Medline, EMBASE, and the Cochrane Controlled Clinical Trials Register. Additional sources were sought from experts. The inclusion criteria were randomized controlled trials, mortality reported as an outcome, pre-emptive haemodynamic intervention, and cardiac surgical population. Included studies were examined in full and subjected to quantifiable analysis, subgroup analysis, and sensitivity analysis where possible. Data synthesis was obtained by using odds ratio (OR) and mean difference (MD) for continuous data with 95% confidence interval (CI) utilizing a random-effects model. RESULTS: From 4986 potential studies, 5 met all the inclusion criteria (699 patients). The quantitative analysis showed that the use of GDT reduced the postoperative complication rate (OR 0.33, 95% CI 0.15-0.73; P=0,006) and hospital length of stay (MD -2.44, 95% CI -4.03 to -0.84; P=0,003). There was no significant reduction in mortality. CONCLUSION: The use of pre-emptive GDT in cardiac surgery reduces morbidity and hospital length of stay.

Raised serum cardiac troponin I concentrations predict hospital mortality in intensive care unit patients.

BACKGROUND: Recent work suggests that increased plasma concentrations of cardiac troponin I (cTnI) are common in critically ill patients and are associated with poor outcome. We measured the frequency of increased plasma cTnI concentrations during patients' stay in a mixed medical/surgical intensive care unit (ICU) and compared our findings with hospital mortality. METHODS: Basic details, organ support, and hospital mortality were recorded for all patients treated in ICU during a 6 month period. cTnI concentrations were sampled daily for all patients, using 0.04 µg litre(-1) as the upper limit of normal, and 0.12 µg litre(-1) as an additional stratification point. RESULTS: Of 663 patients, 54% were male, with a mean (sd) age of 60 (18) yr, 65% were surgical patients, and the median Acute Physiology and Chronic Ill Health II (APACHE II) score was 15 (inter-quartile range 12-20). Increased cTnI concentrations were found in 345 patients (52%) while in ICU. One hundred and twenty patients (18%) died in hospital. cTnI concentration >0.04 µg litre(-1) was associated with reduced odds of hospital survival, independent of age, medical admission, unplanned admission, APACHE II score, mechanical ventilation, and haemofiltration (adjusted odds ratio 0.25, 95% confidence interval 0.08-0.75, P=0.014). Stratification by the degree of cTnI increase revealed an incremental trend towards a lower odds of hospital survival, including for patients with 'minor' elevations of cTnI (0.05-0.12 µg litre(-1)). CONCLUSIONS: Increased serum cTnI concentrations during ICU stay independently predicts hospital mortality, even when the threshold is low. We found a trend towards an association between 'minor' elevations in cTnI and higher in-hospital mortality.

Alzheimer's Disease Prevention Health Coaching.

BACKGROUND: Widespread lifestyle risk reduction at the community level is considered effective in decreasing Alzheimer's disease (AD). To address the limited use of risk deduction in AD, this study aimed to explore the feasibility of community-level implementation. Diverse older adults (60+) living in Richmond, VA, with incomes below $12,000/year and managing diabetic/cardiovascular symptoms were offered weekly lifestyle telephone-health coaching for 12-weeks in 2019-2020 (Phase 1). The health coaching sessions were framed to provide AD lifestyle risk reduction education, goal setting, and support: motivations and self-efficacy. The study sample (n=40, mean age 68 years (range: 60-76 years)) was 90% African American/Black (n=36), 100% Non-Hispanic, and 45% males (n=18). Twenty-five participants (60%) reported experiencing some/often memory problems in the last 12-months. Thirty-nine (95%) of subjects successfully participated in coaching sessions; on average, 11 (91.9%) sessions per subject were completed. Participants provided positive anecdotal feedback and stated the need for continued health coaching. Consequently, n=30 (75%) of the original sample consented to continued health coaching during the 2020-2021 COVID-19 pandemic (Phase 2). All study subjects were examined at baseline (Time 1), 3-month (Time 2), covid-baseline (Time 3), and 3-months postcovid-baseline (Time 4). Repeated Measures ANOVAs were done to examine Time and Time*Memory Status effects. RESULTS: There was a total risk reduction at Phase 1 (F=9.26; p=.004; effect size=.19). At Phase 2, alcohol use decreased (p=.05), quadratic time effects were observed in physical activity (p=.01-.02), and cubic time effects were observed in depression (p=.02). Overall, total risk reduction in Phase 2 was observed at F=5.05; p=.03 effect size=.16. Pre/post-test analyses indicated improvement in Memory Problem Time Interaction (p=.007), AD knowledge (p=.01-.03), and Tired Days (p=.04) across Phase 1. There was also improvement in Social Isolation Time Interaction (p=.03); Tobacco Addiction (p=.001); Poor Mental Health Days (p=.05), and Worried Days Time Interaction (p=.02-.01) across Phase 2. Between subject Memory Status effects, indicating poorer baseline levels for individuals reporting memory problems had greater improvement seen in memory complaints (p=.001), poor mental health days (.02), and tired days (.003-.01). CONCLUSIONS: This preliminary work creates the impetus for future large-scale lifestyle AD risk reduction investigations to mitigate and improve modifiable AD risk among low-income, diverse older adults, including individuals reporting memory problems. Our findings surrounding participant engagement and positive trends in AD risk reduction support the hypothesis that telephone-based health coaching is a practical and feasible AD risk reduction intervention.

Differences in Mate Pairings of Hatchery- and Natural-Origin Coho Salmon Inferred from Offspring Genotypes.

Captive breeding can affect how sexual selection acts on subsequent generations. One context where this is important is in fish hatcheries. In many salmon hatcheries, spawning is controlled artificially and offspring are reared in captivity before release into the wild. While previous studies have suggested that hatchery- and natural-origin fish may make different mate choice decisions, it remains to be determined how hatchery fish may be making different mate choice decisions compared with natural-origin fish at a genetic level. Using genotyping-by-sequencing, we identify single-nucleotide polymorphisms (SNPs) associated with variation in mate pairings from a natural context involving hatchery- and natural-origin coho salmon (Oncorhynchus kisutch). In both natural-origin and hatchery mate pairs, we observed more SNPs with negative assortment than positive assortment. However, only 3% of the negative assortment SNPs were shared between the two mating groups, and 1% of the positive assortment SNPs were shared between the two mating groups, indicating divergence in mating cues between wild and hatchery-raised salmon. These findings shed light on mate choice in general and may have important implications in the conservation management of species as well as for improving other captive breeding scenarios. There remains much to discover about mate choice in salmon and research described here reflects our intent to test the potential of ongoing advances in population genomics to develop new hatchery practices that may improve the performance of hatchery offspring, lessening the differences and thus potential impacts upon wild stocks.

Is Resident-Driven Inpatient Care More Expensive? Challenging a Long-Held Assumption.

PURPOSE: The financial impact of graduate medical education (GME) on teaching hospitals remains poorly understood, while calls for increased federal support continue alongside legislative threats to reduce funding. Despite studies suggesting that residents are more "economical" than alternative providers, GME is widely believed to be an expensive investment. Assumptions that residents increase the cost of patient care have persisted in the absence of convincing evidence to the contrary. Thus, the authors sought to examine resident influence on patient care costs by comparing costs between a resident-driven service (RS) and a nonresident-covered service (NRS), with attention to clinical outcomes and how potential cost differences relate to the utilization of resources, length of stay (LOS), and other factors. METHOD: This prospective study compared costs and clinical outcomes of internal medicine patients admitted to an RS versus an NRS at Massachusetts General Hospital (July 1, 2016-June 30, 2017). Total variable direct costs of inpatient admission was the primary outcome measure. LOS; 30-day readmission rate; utilization related to diagnostic radiology, pharmaceuticals, and clinical labs; and other outcome measures were also compared. Linear regression models quantified the relationship between log-transformed variable direct costs and service. RESULTS: Baseline characteristics of 5,448 patients on the 2 services (3,250 on an RS and 2,198 on an NRS) were similar. On an RS, patient care costs were slightly less and LOS was slightly shorter than on an NRS, with no significant differences in hospital mortality or 30-day readmission rate detected. Resource utilization was comparable between the services. CONCLUSIONS: These findings undermine long-held assumptions that residents increase the cost of patient care. Though not generalizable to ambulatory settings or other specialties, this study can help inform hospital decision making around sponsorship of GME programs, especially if federal funding for GME remains capped or is subject to additional reductions.

C-reactive protein as a predictor of outcome after discharge from the intensive care: a prospective observational study.

BACKGROUND: Recent studies have found plasma C-reactive protein (CRP) to be a predictor of outcome after discharge from the intensive care unit (ICU). To assess the generalizability of this finding, we assessed the value of CRP on the day of ICU discharge as a predictor of unplanned ICU readmission and unexpected death within 2 weeks. Plasma albumin and white cell count at discharge were also considered as markers associated with ongoing inflammation. METHODS: This was a single-centre observational study involving a medical-surgical ICU in a university teaching hospital. Data were prospectively collected from 1487 admissions involving 1401 patients over a 12 month period. Patients' admission details and APACHE II score were collected in addition to plasma CRP, white cell count, and albumin values from the day of discharge from ICU. We assessed the difference in these variables between patients who were readmitted, who died unexpectedly, and those who did not. RESULTS: We found that 9.9% of patients discharged were either readmitted (7.0%) or died unexpectedly (2.9%). Patients who were readmitted had a lower plasma albumin concentration [20 (16, 24) vs 22 (19, 27), P<0.001] and a higher admission APACHE II score [median (inter-quartile range, IQR) 16.5 (13, 21) vs 15 (12, 18), P=0.02]. Patients who died unexpectedly on the ward were older [mean (sd): 76 (12) vs 59 (19), P<0.001] and had a higher APACHE II score [21 (17.25, 26) vs 15 (12, 18), P<0.001]. There was not a statistically significant difference in CRP concentration between patients who either required ICU readmissions or died unexpectedly on the ward and those who did not. CONCLUSIONS: In a mixed medical-surgical intensive care, plasma CRP measured at the day of discharge from intensive care is not a predictor of readmissions or deaths.