Fast Eating Is Associated with Increased BMI among High-School Students

Fast self-reported eating rate (SRER) has been associated with increased adiposity in children and adults. No studies have been conducted among high-school students, and SRER has not been validated vs. objective eating rate (OBER) in such populations. The objectives were to investigate (among high-school student populations) the association between OBER and BMI z-scores (BMIz), the validity of SRER vs. OBER, and potential differences in BMIz between SRER categories. Three studies were conducted. Study 1 included 116 Swedish students (mean ± SD age: 16.5 ± 0.8, 59% females) who were eating school lunch. Food intake and meal duration were objectively recorded, and OBER was calculated. Additionally, students provided SRER. Study 2 included students (n = 50, mean ± SD age: 16.7 ± 0.6, 58% females) from Study 1 who ate another objectively recorded school lunch. Study 3 included 1832 high-school students (mean ± SD age: 15.8 ± 0.9, 51% females) from Sweden (n = 748) and Greece (n = 1084) who provided SRER. In Study 1, students with BMIz ≥ 0 had faster OBER vs. students with BMIz < 0 (mean difference: +7.7 g/min or +27%, p = 0.012), while students with fast SRER had higher OBER vs. students with slow SRER (mean difference: +13.7 g/min or +56%, p = 0.001). However, there was “minimal” agreement between SRER and OBER categories (κ = 0.31, p < 0.001). In Study 2, OBER during lunch 1 had a “large” correlation with OBER during lunch 2 (r = 0.75, p < 0.001). In Study 3, fast SRER students had higher BMIz vs. slow SRER students (mean difference: 0.37, p < 0.001). Similar observations were found among both Swedish and Greek students. For the first time in high-school students, we confirm the association between fast eating and increased adiposity. Our validation analysis suggests that SRER could be used as a proxy for OBER in studies with large sample sizes on a group level. With smaller samples, OBER should be used instead. To assess eating rate on an individual level, OBER can be used while SRER should be avoided.     

Leukocyte activation by isolated hyperthermic liver and limb perfusion due to malignancy

Fourteen patients with liver tumor malignancy and sixteen patients with malignant melanoma localized to one limb were studied regarding leukocyte activation with the release of polymorphonuclear neutrophilic (PMN) elastase and of neopterin and formation of cytokines (TNF- and Il-6) during the surgical treatment. Patients undergoing liver resection (n=10), abdominal hysterectomy (n=10), or hip replacement surgery (n=10) served as control groups. Isolated hyperthermic liver perfusion was performed with cytostatic-containing perfusate (melphalan and cisplatinum). Patients with recurrent malignant melanoma confined to one limb underwent isolated hyperthermic limb perfusion with cytostatic-containing perfusate (melphalan). Blood samples for determination of PMN elastase, neopterin, TNF-, and IL-6 were drawn from the patients preoperatively, 1 minute before the start of the perfusion, 60 and 120 minutes after the start of the perfusion, and 24 hours postoperatively. Samples from the perfusate were drawn 60 minutes after the start of the perfusion. High concentrations of plasma PMN clastase were found both in patients undergoing liver and limb perfusion and in patients undergoing liver resection surgery. Elevated concentrations of Il-6 were found in the patients undergoing liver perfusion and in patients undergoing liver resection. In none of the patients were there increased concentrations of neopterin or TNF-. The perfusate contained high concentrations of PMN elastase, neopterin, and IL-6. This study also demonstrated that major surgery leads to elevated concentrations of PMN elastase and IL-6. An increase of PMN elastase and IL-6 was seen in response to perfusion and to surgical trauma.

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Resumen Catorce pacientes con tumores malignos del hígado y 16 pacientes con melanoma maligno localizado en una extremidad fueron estudiados en relación con la activación de leucocitos con liberación de elastasa de PMN y de neopterina y la formación de citocinas (FNT- e IL-6) en el curso del tratamiento quirúrgico. Pacientes sometidos a resección del hígado (n=10), histerectomía abdominal (n=10) y reemplazo de cadera (n=10) sirvieron como grupos control. Se realizó perfusión hipertérmica aislada del hígado con perfusato citostácico (melfalán y cisplatino). Los pacientes con melanoma maligno recurrente confinado a una extremidad fueron sometidos a perfusión hipertérmica aislada de la extremidad con perfusato citostácico (melfalán). Se tomaron muestras de sangre para determinación preoperatoria de elastasa de PMN, neopterina, FNT- e IL-6, un minuto antes de comenzar la perfusión, 60 y 120 minutos después del comienzo de la perfusión y 24 horas después de la operación. Se tomaron muestras del perfusato a los 60 minutos luego del comienzo de la perfusión. Se encontraron altas concentraciones de elastasa de PMN tanto en los pacientes sometidos a perfusión hepática o de la extremidad, como en los pacientes sometidos a resección hepática. Se encontraron concentraciones elevadas de IL-6 en los pacientes sometidos a perfusión hepática y en los pacientes sometidos a resección del hígado. En ningún paciente se encontraron concentraciones aumentadas de neopterina o de FNT-. El perfusato contenía altas concentraciones de elastasa de PMN, neopterina e IL-6. Se encontró un aumento en la elastasa de PMN y en la IL-6 en respuesta a la perfusión y al trauma quirúrgico.

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Résumé Quatorze patients ayant une tumeur maligne du foie et 16 patients ayant un mélanome malin localisé à une extrémité ont été étudiés en ce qui concerne l'activation des leucocytes associée à un relargage d'élastase PMN et de néoptérine ainsi que la formation de cytokinines (TNF- et IL-6) pendant le traitement chirurgical. Trente patients avant eu soit une résection hépatique (n=10), soit une hystérectomie abdominale (n=10) ou une prothèse de hanche (n=10) ont servi de témoins. On a perfusé le foie avec un perfusât de cytostatiques (mélphalane et cis-platine). Les patients ayant un mélanome malin d'une extrémité ont eu une perfusion isolée hyperthermique avec une perfusion de cytostatique (mélphanane). Des échantillons du sang ont été retirés pour déterminer les taux d'élastase PMN, de la néoptérine, du TNF-, et de l'IL-6 en préopératoire, une minute avant le début de la perfusion, 60 et 120 minutes après le début de la perfusion, et 24 heures postopératoirement. Des échantillons ont été retirés 60 minutes après le début de la perfusion. Des concentration élevées d'élastase PMN ont été retrouvées à la fois chez les patients ayant une perfusion hépatique et de l'extrémité et chez les patients ayant eu une résection du foie. Des concentration élevées en IL-6 ont été retrouvées chez le patient ayant une perfusion du foie et chez le patient ayant une résection hépatique. Les concentrations en néoptérine et en TNF- n'étaient pas élevées. Le liquide de perfusion contenait des concentrations élevées en élastase PMN, néoptérine et en IL-6. Cette étude démontre aussi que la chirurgie majeure est associée avec des concentrations élevées en PMN elastase et IL-6. Une augmentation en PMN-élastase et en IL-6 a été retrouvée en réponse à la perfusion et au traumatisme chirurgical.

     

Early-life exposures associated with antibiotic use and risk of subsequent Crohn's disease

Objective. An inappropriate immune response to normal bowel flora is implicated in the etiology of Crohn's disease. Tolerance to bowel flora develops in infancy, so factors disrupting normal patterns of bowel colonization may increase the risk of Crohn's disease. The aim of this study was to test the hypothesis that antibiotic therapy between birth and age 5 years may disrupt the pattern of bowel colonization and increase the risk of Crohn's disease. Material and methods. Some 1098 patients with Crohn's disease and 6550 controls matched by delivery unit, year of birth, sex, and born between 1973 and 1997 were identified through the Swedish population registers. Seven inpatient diagnoses between birth and age 5 years associated with antibiotic therapy were identified by prospectively recorded data. Results. Of the seven diagnoses, only pneumonia and otitis media were sufficiently common for use in the analyses. Pneumonia and otitis media were not independent of each other in their association with Crohn's disease and the more important association was with pneumonia. Pneumonia by age 5 years was statistically significantly associated with both pediatric- and adult Crohn's disease, with odds ratios (and 95% CI) of 2.74 (1.04–7.21) and 4.94 (1.83–13.23), respectively. Pneumonia after age 5 years was not statistically significantly associated with Crohn's disease. Conclusions. Pneumonia prior to age 5 years, but not later, was associated with subsequent Crohn's disease and this may represent either susceptibility or causation. The results are consistent with early exposures influencing immune function, such as through disruption of bowel colonization, and thus increasing the risk of Crohn's disease.     

Sensitivity of regression calibration to non‐perfect validation data with application to the Norwegian Women and Cancer Study

Measurement error occurs when we observe error‐prone surrogates, rather than true values. It is common in observational studies and especially so in epidemiology, in nutritional epidemiology in particular. Correcting for measurement error has become common, and regression calibration is the most popular way to account for measurement error in continuous covariates. We consider its use in the context where there are validation data, which are used to calibrate the true values given the observed covariates. We allow for the case that the true value itself may not be observed in the validation data, but instead, a so‐called reference measure is observed. The regression calibration method relies on certain assumptions.This paper examines possible biases in regression calibration estimators when some of these assumptions are violated. More specifically, we allow for the fact that (i) the reference measure may not necessarily be an ‘alloyed gold standard’ (i.e., unbiased) for the true value; (ii) there may be correlated random subject effects contributing to the surrogate and reference measures in the validation data; and (iii) the calibration model itself may not be the same in the validation study as in the main study; that is, it is not transportable. We expand on previous work to provide a general result, which characterizes potential bias in the regression calibration estimators as a result of any combination of the violations aforementioned. We then illustrate some of the general results with data from the Norwegian Women and Cancer Study. Copyright © 2015 John Wiley & Sons, Ltd.     

Sex-related differences in diabetic kidney disease: A review on the mechanisms and potential therapeutic implications

Sexual dimorphism may play a key role in the pathogenesis of diabetic kidney disease (DKD) and explain differences observed in disease phenotypes, responses to interventions, and disease progression between men and women with diabetes. Therefore, omitting the consideration of sex as a biological factor may result in delayed diagnoses and suboptimal therapies. This review will summarize the effects of sexual dimorphism on putative metabolic and molecular mechanisms underlying DKD, and the potential implications of these differences on therapeutic interventions. To successfully implement precision medicine, we require a better understanding of sexual dimorphism in the pathophysiologic progression of DKD. Such insights can unveil sex-specific therapeutic targets that have the potential to maximize efficacy while minimizing adverse events.