Prevalence of hypoxia and correlation with glycolytic metabolism and angiogenic biomarkers in metastatic colorectal carcinoma.

PURPOSE: Hypoxia is associated with aggressive tumour behaviour and can influence response to systemic therapy and radiotherapy. The prevalence of hypoxia in metastatic colorectal cancer is poorly understood, and the relationship of hypoxia to patient outcomes has not been clearly established. The aims of the study were to evaluate hypoxia in metastatic colorectal cancer with [18F]Fluoromisonidazole ([18F]FMISO PET) and correlate these findings with glycolytic metabolism ([18F]FDG PET) and angiogenic blood biomarkers and patient outcomes. METHODS: Patients with metastatic colorectal cancer received routine staging investigations and both [18F] FMISO PET and [18F] FDG PET scans. Correlative blood specimens were also obtained at the time of the [18F] FMISO PET scan. Patient follow-up was performed to establish progression-free survival. RESULTS: A total of 40 patients were recruited into the trial. [18F]FMISO and [18F]FDG PET scans showed a significant correlation of SUVmax (p = 0.003). A significant correlation of progression-free survival and [18F] FMISO TNR (p = 0.02) and overall survival with [18F]FMISO TNR (p = 0.003) and [18F]FDG TGV (p = 0.02) was observed. Serum levels of osteopontin, but not VEGF, correlated with [18F] FMISO and [18F]FDG PET scan parameters. CONCLUSION: [18F]FMISO PET uptake in metastatic colorectal cancer significantly correlates with glycolytic metabolism and is predictive of progression-free and overall survival. These findings have implications for the assessment and treatment of metastatic colorectal cancer patients with novel therapies which affect tumour angiogenesis and hypoxia.

Effects of universal masking on Massachusetts healthcare workers' COVID-19 incidence.

BACKGROUND: Healthcare workers (HCWs) and other essential workers are at risk of occupational infection during the COVID-19 pandemic. Several infection control strategies have been implemented. Evidence shows that universal masking can mitigate COVID-19 infection, though existing research is limited by secular trend bias. AIMS: To investigate the effect of hospital universal masking on COVID-19 incidence among HCWs compared to the general population. METHODS: We compared the 7-day average incidence rates between a Massachusetts (USA) healthcare system and Massachusetts residents statewide. The study period was from 17 March (the date of first incident case in the healthcare system) to 6 May (the date Massachusetts implemented public masking). The healthcare system implemented universal masking on 26 March, we allotted a 5-day lag for effect onset and peak COVID-19 incidence in Massachusetts was 20 April. Thus, we categorized 17-31 March as the pre-intervention phase, 1-20 April the intervention phase and 21 April to 6 May the epidemic decline phase. Temporal incidence trends (i.e. 7-day average slopes) were compared using standardized coefficients from linear regression models. RESULTS: The standardized coefficients were similar between the healthcare system and the state in both the pre-intervention and epidemic decline phases. During the intervention phase, the healthcare system's epidemic slope became negative (standardized ß: -0.68, 95% CI: -1.06 to -0.31), while Massachusetts' slope remained positive (standardized ß: 0.99, 95% CI: 0.94 to 1.05). CONCLUSIONS: Universal masking was associated with a decreasing COVID-19 incidence trend among HCWs, while the infection rate continued to rise in the surrounding community.

Recruit fitness and police academy performance: a prospective validation study.

BACKGROUND: Police academies need fit recruits to successfully engage in training activities. In a previous retrospective study, we documented that recruits with poor fitness at entry to the academy had significantly lower graduation rates, and we also suggested evidence-based entry-level fitness recommendations. AIMS: To validate our findings in a prospective cohort of police recruits. METHODS: Recruits entering Massachusetts municipal police academies during 2015-16 were followed prospectively until they dropped out, failed or successfully graduated their academy classes. Entry-level fitness was quantified at the start of each training class using: body composition, push-ups, sit-ups, sit-and-reach and 1.5-mile run time. The primary outcome of interest was the odds of failure (not successfully graduating from an academy). We used logistic regression to assess the probability of not graduating, based on entry-level fitness. RESULTS: On average, successful graduates were leaner and possessed better overall entry-level fitness. After adjusting for age, gender and body mass index, several fitness measures were strongly associated with academy failure: fewer sit-ups completed (OR 9.6 (95% CI 3.5-26.3) (≤15 versus 41-60)); fewer push-ups completed (OR 6.7 (95% CI 2.5-17.5) (≤20 versus 41-60)); and slower run times (OR 18.4 (95% CI 6.8-50.2) (1.5 miles in > 15 min 20 s versus 10 min 37 s to 12 min 33 s)). The prospective study results supported previously suggested minimum entry-level fitness (95% graduation rate) and target (98% graduation rate) recommendations. CONCLUSIONS: Push-ups completed and 1.5-mile run time at police academy entry were successfully validated as predictors of successful academy graduation, while sit-ups were also a strong independent predictor in the prospective study.

Obesity and Dental Caries in Young Children in Plymouth, United Kingdom: A Spatial Analysis.

OBJECTIVE: To examine the spatial clustering of obesity and dental caries in young children in Plymouth, United Kingdom, to evaluate the association between these conditions and deprivation, and explore the impact of neighbourhood-level characteristics on their distribution. BASIC RESEARCH DESIGN: Cross-sectional study analysing data from the National Child Measurement Programme (N=2427) and the Local Dental Health Survey (N=1425). The association of deprivation with weight status and caries was determined at individual and area level, using ANOVA and Poisson models. The overall spatial clustering was assessed using a modified version of the Global Moran's I, while clusters were located through Local Indicators of Spatial Association. Spatial autocorrelation was assessed using the variograms of the raw values. Log-linear Poisson models were fitted to assess the significance of neighbourhood characteristics on overweight/obesity and caries distribution. RESULTS: At an individual level, deprivation was not associated with BMI z-scores but was a significant predictor of caries (p⟨0.05). However, at area level, deprivation related to the rates of both conditions. A significant positive autocorrelation was observed across neighbourhoods for caries. The variograms suggested spatial autocorrelations up to 2.5 km and 3 km for overweight/obesity and caries, respectively. Among several neighbourhood characteristics, the proportion of people on benefits was found to be a significant predictor of caries rates. CONCLUSIONS: Our results underline the importance of considering geographic location and characteristics of the broader environment when developing strategies to target obesity and caries.

Recruit Fitness as a Predictor of Police Academy Graduation.

BACKGROUND: Suboptimal recruit fitness may be a risk factor for poor performance, injury, illness, and lost time during police academy training. AIMS: To assess the probability of successful completion and graduation from a police academy as a function of recruits' baseline fitness levels at the time of academy entry. METHODS: Retrospective study where all available records from recruit training courses held (2006-2012) at all Massachusetts municipal police academies were reviewed and analysed. Entry fitness levels were quantified from the following measures, as recorded at the start of each training class: body composition, push-ups, sit-ups, sit-and-reach, and 1.5-mile run-time. The primary outcome of interest was the odds of not successfully graduating from an academy. We used generalized linear mixed models in order to fit logistic regression models with random intercepts for assessing the probability of not graduating, based on entry-level fitness. The primary analyses were restricted to recruits with complete entry-level fitness data. RESULTS: The fitness measures most strongly associated with academy failure were lesser number of push-ups completed (odds ratio [OR] = 5.2, 95% confidence interval [CI] 2.3-11.7, for 20 versus 41-60 push-ups) and slower run times (OR = 3.8, 95% CI 1.8-7.8, [1.5 mile run time of ≥15'20″] versus [12'33″ to 10'37″]). CONCLUSIONS: Baseline pushups and 1.5-mile run-time showed the best ability to predict successful academy graduation, especially when considered together. Future research should include prospective validation of entry-level fitness as a predictor of subsequent police academy success.

Adiponectin, C-reactive protein, fibrinogen and tissue plasminogen activator antigen levels among glucose-intolerant women with and without histories of gestational diabetes.

AIM: To examine concentrations of biomarkers (adiponectin, C-reactive protein, fibrinogen and tissue plasminogen-activator antigen) associated with glucose homeostasis and diabetes risk by history of gestational diabetes (GDM). METHODS: We conducted a secondary analysis of the Diabetes Prevention Program, a randomized trial of lifestyle intervention or metformin for diabetes prevention. At baseline, participants were overweight and had impaired glucose tolerance. Biomarkers at baseline and 1 year after enrolment were compared between parous women with (n = 350) and without histories of GDM (n = 1466). Cox proportional hazard models evaluated whether history of GDM was associated with diabetes risk, after adjustment for baseline biomarker levels as well as for change in biomarker levels, demographic factors and anthropometrics. RESULTS: At baseline, women with histories of GDM had lower adiponectin (7.5 µg/ml vs. 8.7 µg/ml; p < 0.0001) and greater log C-reactive protein (-0.90 mg/l vs. -0.78 mg/l, p = 0.04) levels than women without histories of GDM, but these associations did not persist after adjustment for demographic factors. Fibrinogen and tissue plasminogen-activator antigen were similar between women with and without histories of GDM. Women with and without histories of GDM had a similar pattern of changes in biomarkers within randomization arm. Adjustment for age, race/ethnicity, baseline weight, change in weight, baseline biomarker level and change in biomarker level did not significantly alter the association between history of GDM, and diabetes risk. CONCLUSIONS: Among women with impaired glucose tolerance, biomarkers in women with and without histories of GDM are similar and respond similarly to lifestyle changes and metformin. Adjustment for biomarker levels did not explain the higher risk of diabetes observed in women with histories of GDM.

A randomised controlled trial of peri-operative lidocaine infusions for open radical prostatectomy.

We allocated 76 men scheduled for radical retropubic prostatectomy to peri-operative lidocaine 2% or saline 0.9%: a pre-operative 0.075 ml.kg(-1) intravenous bolus; an intra-operative intravenous infusion at 0.075 ml.kg(-1) .h(-1) ; and 24 hours' postoperative subcutaneous infusion at 0.075 ml.kg(-1) .h(-1) . Lidocaine reduced the postoperative hospital stay by a mean (95% CI) of 1.3 (0.3-2.4) days, p = 0.017, from a mean (SD) of 4.6 (3.2) days with saline. There were no significant differences in pain at rest or on coughing at 24 h. [corrected]. Lidocaine reduced 24-h morphine consumption by a mean (95% CI) of 13.9 (2.2-25.7) mg, p = 0.021, from a mean (SD) of 52.3 (26.9) mg with saline. There were no differences in other outcomes.

Early Outcome of Liver Resections in Octogenarians.

BACKGROUND: Reports on safety and feasibility of liver resection in patients 80 years and older are very limited. OBJECTIVE: Here, we intend to analyze the perioperative outcomes of liver resections in octogenarians performed at a single tertiary level teaching hospital over a ten years period. METHOD: Retrospective review of the medical records (between 2004 to 2014) of patients of the defined age group was performed. Clinicopathological features, indications, extent of resections, intraoperative parameters, postoperative complications and final outcome were analyzed. Findings were compared with similar studies published in literature. RESULT: Total 19 (11 male, 8 female, maximum age 85 years) patients of the study group underwent liver resection during the defined period. Commonest indication was colorectal liver metastasis (9 patients). One patient had pancreaticodudenectomy for periampullary malignancy four years prior to present with liver metastasis and subsequently had liver resection for recurrence of disease. Except one, all had open surgery. Types of resection ranged from sub segmental to major right (8 patients) and left (1 patient) hepatectomy. Total 3 (27%) out of 11 patients on whom drain was not placed required radiological drainage of abdominal collection. One patient developed liver abscess postoperatively and was also successfully drained under radiological guidance. Only 2 (10.5%) had prolonged Intensive Care Unit (ICU) stay and remaining patients were discharged to ward after 24 hrs of observation in high dependency/Intensive care unit. Median hospital stay was 11 days. Postoperative complications were 3 of grade II, 4 of grade IIIa, 1 of IIIb and 2 of IVa. Total 9 patients were discharged to rehabilitation centers and remaining 10 could be discharged home. There was 0% mortality. CONCLUSION: In appropriately selected cases, when performed in specialized tertiary centers excellent perioperative outcomes of liver resections can be achieved even in patients of 80 years of age and above.

Household cleaning activities as noningestion exposure determinants of urinary trihalomethanes.

Previous epidemiological studies linking drinking water total trihalomethanes (THM) with pregnancy disorders or bladder cancer have not accounted for specific household cleaning activities that could enhance THM exposures. We examined the relation between household cleaning activities (washing dishes/clothes, mopping, toilet cleaning, and washing windows/surfaces) and urinary THM concentrations accounting for water sources, uses, and demographics. A cross-sectional study (n = 326) was conducted during the summer in Nicosia, Cyprus, linking household addresses to the geocoded public water pipe network, individual household tap water, and urinary THM measurements. Household tap water THM concentrations ranged between 3-129 µg L(-1), while the median (Q1, Q3) creatinine-adjusted urinary THM concentration in females (669 ng g(-1) (353, 1377)) was significantly (p < 0.001) higher than that in males (399 ng g(-1), (256, 681)). Exposure assessment, based on THM exposure equivalency units, showed that hand dishwashing, mopping, and toilet cleaning significantly (p < 0.001) increased urinary THM levels. The effect of dishwashing by females ≥36 y of age remained significant, even after adjusting for potential confounders. No significant (p > 0.05) association was observed between ingestion-based THM exposure equivalency units and urinary THM. Noningestion routes of THM exposures during performance of routine household cleaning activities were shown for the first time to exert a major influence on urinary THM levels. It is warranted that future pregnancy-birth cohorts include monitoring of noningestion household THM exposures in their study design.

Association between water consumption from polycarbonate containers and bisphenol A intake during harsh environmental conditions in summer.

With the exception of polycarbonate (PC) baby bottles, little attention has been paid to bisphenol A (BPA) intake from packaged water consumption (PC water dispensers), especially during summer weather conditions. We determined the magnitude and variability of urinary BPA concentrations during summer in 35 healthy individuals largely relying upon PC packaged water to satisfy their potable needs. We used liquid chromatography-tandem mass spectrometry to measure urinary BPA concentrations. A questionnaire was administered in July/August and a spot urine sample was collected on the same day and 7 days after the completion of the interview (without intervention). Linear regression was performed to assess the association of variables, such as water consumption from different sources, on urinary BPA levels for the average of the two urine samples. A significant positive association (p = 0.017) was observed between PC water consumption and urinary BPA levels in females, even after adjusting for covariates in a multivariate regression model. The geometric mean of daily BPA intake back-calculated from urinary BPA data was 118 ng · (kg bw)(-1) · day(-1), nearly double the average intake levels observed in biomonitoring studies worldwide. High urinary BPA levels were partially ascribed to summer's high PC water consumption and weather characteristics (high temperatures, >40 °C; very high UV index values, >8), which could be causing BPA leaching from PC. It is suggested that PC-based water consumption could serve as a proxy for urinary BPA, although the magnitude of its relative contribution to overall daily intake requires further investigation.

Common variants in genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1/2), adiponectin concentrations, and diabetes incidence in the Diabetes Prevention Program.

AIMS: Baseline adiponectin concentrations predict incident Type 2 diabetes mellitus in the Diabetes Prevention Program. We tested the hypothesis that common variants in the genes encoding adiponectin (ADIPOQ) and its receptors (ADIPOR1, ADIPOR2) would associate with circulating adiponectin concentrations and/or with diabetes incidence in the Diabetes Prevention Program population. METHODS: Seventy-seven tagging single-nucleotide polymorphisms (SNPs) in ADIPOQ (24), ADIPOR1 (22) and ADIPOR2 (31) were genotyped. Associations of SNPs with baseline adiponectin concentrations were evaluated using linear modelling. Associations of SNPs with diabetes incidence were evaluated using Cox proportional hazards modelling. RESULTS: Thirteen of 24 ADIPOQ SNPs were significantly associated with baseline adiponectin concentrations. Multivariable analysis including these 13 SNPs revealed strong independent contributions of rs17366568, rs1648707, rs17373414 and rs1403696 with adiponectin concentrations. However, no ADIPOQ SNPs were directly associated with diabetes incidence. Two ADIPOR1 SNPs (rs1342387 and rs12733285) were associated with ∼18% increased diabetes incidence for carriers of the minor allele without differences across treatment groups, and without any relationship with adiponectin concentrations. CONCLUSIONS: ADIPOQ SNPs are significantly associated with adiponectin concentrations in the Diabetes Prevention Program cohort. This observation extends prior observations from unselected populations of European descent into a broader multi-ethnic population, and confirms the relevance of these variants in an obese/dysglycaemic population. Despite the robust relationship between adiponectin concentrations and diabetes risk in this cohort, variants in ADIPOQ that relate to adiponectin concentrations do not relate to diabetes risk in this population. ADIPOR1 variants exerted significant effects on diabetes risk distinct from any effect of adiponectin concentrations.

Low fitness is associated with exercise abnormalities among asymptomatic firefighters.

BACKGROUND: Low cardiorespiratory fitness (CRF) has been repeatedly linked to cardiovascular morbidity and mortality, while higher CRF levels are protective. This relationship is likely to be highly relevant in firefighters, who have increased risk of cardiovascular disease (CVD) mortality during strenuous emergencies, which can require prolonged periods of near-maximal heart rates (HR) and high workloads. Abnormalities during maximal stress testing could mark future CVD risk during strenuous duties. AIMS: To determine if low CRF among asymptomatic firefighters is associated with higher risk of electrocardiographic (ECG) and autonomic abnormalities during maximal exercise stress testing and recovery. METHODS: Male career firefighters completed a maximal stress test exercising to volitional exhaustion (mean maximal age-predicted HR achieved 98%, standard deviation (SD) = 6.5). CRF was measured as maximal metabolic equivalents (METS) achieved. Abnormal exercise tests included the following: abnormal HR recovery; chronotropic insufficiency; exaggerated blood pressure response; and ECG abnormalities. The relationship of CRF to stress testing abnormalities was analysed using peak METS categories and peak METS as a continuous variable after adjusting for age, body mass index (BMI) and metabolic syndrome (MetSyn). RESULTS: There were 1149 study participants. CRF was inversely associated with the risk of both ECG and autonomic exercise testing abnormalities before and after adjustment for age, BMI and MetSyn. CONCLUSIONS: Firefighters with lower CRF are significantly more prone to exhibit abnormal stress test parameters, which may indicate higher future risk of cardiovascular events. As such, firefighters with low CRF (≤ 12 METS) should receive cardiovascular risk reduction, including efforts to improve their CRF.

Associations of fluid amount, type, and balance and acute kidney injury in patients undergoing major surgery.

Fluid administration has been reported to be associated with an increased risk of acute kidney injury (AKI). We assessed whether, after correction for fluid balance, amount and chloride content of fluids administered have an independent association with AKI. We performed an observational study in patients after major surgery assessing the independent association of AKI with volume, chloride content and fluid balance, after adjustment for Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) score, age, elective versus emergency surgery, and duration of surgery. We studied 542 consecutive patients undergoing major surgery. Of these, 476 patients had renal function tested as part of routine clinical care and 53 patients (11.1%) developed postoperative AKI. After adjustments, a 100 ml greater mean daily fluid balance was artificially associated with a 5% decrease in the instantaneous hazard of AKI: adjusted Hazard Ratio (aHR) 0.951, 95% confidence intervals (CI) 0.935 to 0.967, P <0.001. However, after adjustment for the proportion of chloride-restrictive fluids, mean daily fluid amounts and balances, POSSUM morbidity, age, duration and emergency status of surgery, and the confounding effect of fluid balance, every 5% increase in the proportion of chloride-liberal fluid administered was associated with an 8% increase in the instantaneous hazard of AKI (aHR 1.079, 95% CI 1.032 to 1.128, P=0.001), and a 100 ml increase in mean daily fluid amount given was associated with a 6% increase in the instantaneous hazard of AKI (aHR 1.061, 95% CI 1.047 to 1.075, P <0.001). After adjusting for key risk factors and for the confounding effect of fluid balance, greater fluid administration and greater administration of chloride-rich fluid were associated with greater risk of AKI.

Expectations of outcomes in patients with colorectal cancer.

BACKGROUND: Understanding patients' expectations of their treatment is critical to ensure appropriate treatment decisions, and to explore how expectations influence coping, quality of life and well-being. This study aimed to examine these issues related to treatment in patients with colorectal cancer. METHODS: A literature search from January 1946 to September 2016 was performed to identify available data regarding patients' expectations of outcomes following colorectal cancer treatment. A narrative synthesis of the evidence was planned. RESULTS: Of 4337 items initially identified, 20 articles were included in the review. In studies presenting data on overall and short-term survival, patients considerably overestimated prognosis. Patients also had unrealistic expectations of the negative aspects of chemotherapy and stomas. There was marked discordance between patients' and clinicians' expectations regarding chemotherapy, end-of-life care, bowel function and psychosocial outcomes. Level of education was the most consistent factor influencing the accuracy of patients' expectations. CONCLUSION: Patients with colorectal cancer frequently have unrealistic expectations of treatment. Marked disparities exist between patients' and clinicians' expectations of outcomes.

The effect of a surgery-specific cardiac output-guided haemodynamic algorithm on outcomes in patients undergoing pancreaticoduodenectomy in a high-volume centre: a retrospective comparative study.

In this retrospective observational study performed in a high-volume hepatobiliary-pancreatic unit, we evaluated the effect of a surgery-specific goal-directed therapy (GDT) physiologic algorithm on complications and length of hospital stay. We compared patients who underwent pancreaticoduodenectomy with either a standardised Enhanced Recovery After Surgery program (usual care group), or a standardised Enhanced Recovery After Surgery program in combination with a surgery-specific cardiac output-guided algorithm (GDT group). We included 145 consecutive patients: 47 in the GDT group and 98 in the usual care group. Multivariable associations between GDT and lengths of stay and complications were investigated using negative binomial regression. Postoperative complications were common and occurred at similar frequencies amongst the GDT and usual care groups: 64% versus 68% respectively, P=0.71; odds ratio 0.82; (95% confidence interval 0.39-1.70). There were fewer cardiorespiratory complications in the GDT group. Median (interquartile range) length of hospital stay was ten days (8.0-14.0) in the GDT group compared to 13 days (8.8-21.3) in the usual care group, P=0.01. Median (interquartile range) total intraoperative fluid was 3,000 ml (2,050-4,175) in the GDT group compared to 4,500 ml (3,275-5,325) in the usual care group, P <0.0001; but by day one, the median (interquartile range) fluid balance was similar (1,198 ml [700-1,729] in the GDT group versus 977 ml [419-2,044] in the usual care group, P=0.96). Use of vasoactive medications was higher in the GDT group. In our patients undergoing pancreaticoduodenectomy, GDT was associated with restrictive intraoperative fluid intervention, fewer cardiorespiratory complications and a shorter hospital length of stay compared to usual care. However, we could not exclude an influence of surgical caseload, which we have previously found to be an important variable. We also could not relate the increased hospital length of stay to cardiorespiratory complications in individual patients. Therefore, these observational retrospective findings would require confirmation in a prospective randomised study.

Combretastatin A4 prodrug study of effect on the growth and the microvasculature of colorectal liver metastases in a murine model.

Combretastatin A4P (CA4P) is a prodrug that, in active form, binds to tubulin microtubules of capillary endothelial cells. Studies to date indicate it has significant activity as a specific tumor vascular targeting agent. The goals were to assess the effects of CA4P on tumor growth and microvasculature of colorectal liver metastases in the mouse model, using stereological and histological methods to measure tumor growth, and vascular corrosion casting and laser doppler flowmetry to assess effect on the microvasculature. Continuous s.c. infusion of CA4P produced a major reduction in tumor growth. The percentage of the liver occupied by metastases decreased from 20.55 +/- 13.3% in controls to 7.46 +/- 5.99% in treated animals (P = 0.03). Ultrastructural study of tumor microvasculature after a single dose of CA4P revealed marked effects 1 h after treatment. There was loss of patent microvessels at the normal liver-tumor interface. Central microvascular density was reduced, with constriction and tapering of vessels. CA4P appeared to cause no damage to normal liver tissue or vasculature. Tumor blood flow decreased from 37.6 +/- 13.9% in controls to 24.4 +/- 6.1% in tumors >5 mm in diameter, 1 h after treatment with CA4P (P < 0.03). Quantitative histology of tissue at 6 and 24 h after CA4P treatment showed a significant increase in tumor necrosis (48.7 +/- 21% and 55.5 +/- 19% compared with controls, 20.6 +/- 8%; P = 0.01). Continuous infusion with CA4P causes marked reduction in tumor volume. A single dose of CA4P causes major changes of the tumor microvasculature, reduction of tumor blood flow, and increase in tumor necrosis. CA4P has a potential role in the management of patients with liver metastases.

The effects of plasmalyte-148 vs. Hartmann's solution during major liver resection: a multicentre, double-blind, randomized controlled trial.

BACKGROUND: The acid-base, biochemical and hematological effects of crystalloid solutions have not been comprehensively evaluated in patients with liver resection. DESIGN: multicenter, prospective, double-blind randomized controlled trial investigating the biochemical effects of Hartmann's solution (HS) or Plasmalyte-148 (PL) in 60 patients undergoing major liver resection. PRIMARY OUTCOME: base excess immediately after surgery. SECONDARY OUTCOMES: changes in blood biochemistry and hematology. RESULTS: At completion of surgery, patients receiving HS had equivalent mean standard base excess (-1.7±2.2 vs. -0.9±2.3 meq/L; P=0.17) to those treated with PL. However, patients treated with HS were more hyperchloremic (difference 1.7 mmol/L, 95% CI: 0.2 to 3.2, P=0.03) and hyperlactatemic (difference 0.8 mmol/L, 95% CI: 0.2 to 1.3; P=0.01). In contrast, patients receiving PL had higher mean plasma magnesium levels and lower ionized calcium levels. There were no significant differences in pH, bicarbonate, albumin and phosphate levels. Immediately after surgery, mean PT and aPTT were significantly lower in the PL group. Intraoperatively, the median (IQR) blood loss in the PL group was 300 mL (200:413) vs. 500 mL (300:638) in the HS group (P=0.03). Correspondingly, the postoperative hemoglobin was higher in the PL group. Total complications were more frequent in the HS Group (56% vs. 20%, relative risk 2.8; 95% CI: 1.3 to 6.1; P=0.007). CONCLUSION: In liver resection patients, HS and PL led to similar base excess values but different post operative plasma biochemistry and hematology values. Understanding of these effects may help clinicians individualize fluid therapy in these patients.

Steroid Sex Hormones, Sex Hormone-Binding Globulin, and Diabetes Incidence in the Diabetes Prevention Program.

CONTEXT: Steroid sex hormones and SHBG may modify metabolism and diabetes risk, with implications for sex-specific diabetes risk and effects of prevention interventions. OBJECTIVE: This study aimed to evaluate the relationships of steroid sex hormones, SHBG and SHBG single-nucleotide polymorphisms (SNPs) with diabetes risk factors and with progression to diabetes in the Diabetes Prevention Program (DPP). DESIGN AND SETTING: This was a secondary analysis of a multicenter randomized clinical trial involving 27 U.S. academic institutions. PARTICIPANTS: The study included 2898 DPP participants: 969 men, 948 premenopausal women not taking exogenous sex hormones, 550 postmenopausal women not taking exogenous sex hormones, and 431 postmenopausal women taking exogenous sex hormones. INTERVENTIONS: Participants were randomized to receive intensive lifestyle intervention, metformin, or placebo. MAIN OUTCOMES: Associations of steroid sex hormones, SHBG, and SHBG SNPs with glycemia and diabetes risk factors, and with incident diabetes over median 3.0 years (maximum, 5.0 y). RESULTS: T and DHT were inversely associated with fasting glucose in men, and estrone sulfate was directly associated with 2-hour post-challenge glucose in men and premenopausal women. SHBG was associated with fasting glucose in premenopausal women not taking exogenous sex hormones, and in postmenopausal women taking exogenous sex hormones, but not in the other groups. Diabetes incidence was directly associated with estrone and estradiol and inversely with T in men; the association with T was lost after adjustment for waist circumference. Sex steroids were not associated with diabetes outcomes in women. SHBG and SHBG SNPs did not predict incident diabetes in the DPP population. CONCLUSIONS: Estrogens and T predicted diabetes risk in men but not in women. SHBG and its polymorphisms did not predict risk in men or women. Diabetes risk is more potently determined by obesity and glycemia than by sex hormones.

The effect of lifestyle intervention and metformin on preventing or delaying diabetes among women with and without gestational diabetes: the Diabetes Prevention Program outcomes study 10-year follow-up.

CONTEXT: Gestational diabetes (GDM) confers a high risk of type 2 diabetes. In the Diabetes Prevention Program (DPP), intensive lifestyle (ILS) and metformin prevented or delayed diabetes in women with a history of GDM. OBJECTIVE: The objective of the study was to evaluate the impact of ILS and metformin intervention over 10 years in women with and without a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study. DESIGN: This was a randomized controlled clinical trial with an observational follow-up. SETTING: The study was conducted at 27 clinical centers. PARTICIPANTS: Three hundred fifty women with a history of GDM and 1416 women with previous live births but no history of GDM participated in the study. The participants had an elevated body mass index and fasting glucose and impaired glucose tolerance at study entry. INTERVENTIONS: Interventions included placebo, ILS, or metformin. OUTCOMES MEASURE: Outcomes measure was diabetes mellitus. RESULTS: Over 10 years, women with a history of GDM assigned to placebo had a 48% higher risk of developing diabetes compared with women without a history of GDM. In women with a history of GDM, ILS and metformin reduced progression to diabetes compared with placebo by 35% and 40%, respectively. Among women without a history of GDM, ILS reduced the progression to diabetes by 30%, and metformin did not reduce the progression to diabetes. CONCLUSIONS: Women with a history of GDM are at an increased risk of developing diabetes. In women with a history of GDM in the DPP/Diabetes Prevention Program Outcomes Study, both lifestyle and metformin were highly effective in reducing progression to diabetes during a 10-year follow-up period. Among women without a history of GDM, lifestyle but not metformin reduced progression to diabetes.