Dietary Protein Intake and Transition between Frailty States in Octogenarians Living in New Zealand.

Adequate nutritional status may influence progression to frailty. The purpose of this study is to determine the prevalence of frailty and examine the relationship between dietary protein intake and the transition between frailty states and mortality in advanced age. We used data from a longitudinal cohort study of Maori (80-90 years) and non-Maori (85 years). Dietary assessments (24-h multiple pass dietary recalls) were completed at the second year of follow-up (wave 2 and forms the baseline in this study). Frailty was defined using the Fried Frailty criteria. Multi-state modelling examined the association of protein intake and transitions between frailty states and death over four years. Over three quarters of participants were pre-frail or frail at baseline (62% and 16%, respectively). Those who were frail had a higher co-morbidity (p < 0.05), where frailty state changed, 44% showed a worsening of frailty status (robust → pre-frail or pre-frail → frail). Those with higher protein intake (g/kg body weight/day) were less likely to transition from robust to pre-frail [Hazard Ratio (95% Confidence Interval): 0.28 (0.08-0.91)] but also from pre-frail to robust [0.24 (0.06-0.93)]. Increased protein intake was associated with lower risk of transitioning from pre-frailty to death [0.19 (0.04-0.80)], and this association was moderated by energy intake [0.22 (0.03-1.71)]. Higher protein intake in this sample of octogenarians was associated with both better and worse outcomes.

Plasma and Urinary Amino Acid-Derived Catabolites as Potential Biomarkers of Protein and Amino Acid Deficiency in Rats.

OBJECTIVE: Dietary intakes must cover protein and essential amino acid (EAA) requirements. For this purpose, different methods have been developed such as the nitrogen balance method, factorial method, or AA tracer studies. However, these methods are either invasive or imprecise, and the Food and Agriculture Organization of the United Nations (FAO, 2013) recommends new methods and, in particular, metabolomics. The aim of this study is to determine total protein/EAA requirement in the plasma and urine of growing rats. METHODS: 36 weanling rats were fed with diets containing 3, 5, 8, 12, 15, and 20% protein for 3 weeks. During experimentation, urine was collected using metabolic cages, and blood from the portal vein and vena was taken at the end of the experiment. Metabolomics analyses were performed using LC-MS, and the data were analyzed with a multivariate analysis model, partial least Squares (PLS) regression, and independent component-discriminant analysis (ICDA). Each discriminant metabolite identified by PLS or ICDA was tested by one-way ANOVA to evaluate the effect of diet. RESULTS: PLS and ICDA allowed us to identify discriminating metabolites between different diet groups. Protein deficiency led to an increase in the AA catabolism enzyme systems inducing the production of breakdown metabolites in the plasma and urine. CONCLUSION: These results indicate that metabolites are specific for the state of EAA deficiency and sufficiency. Some types of biomarkers such as AA degradation metabolites appear to be specific candidates for protein/EAA requirement.

1H NMR metabolomic and transcriptomic analyses reveal urinary metabolites as biomarker candidates in response to protein undernutrition in adult rats.

Protein undernutrition contributes to the development of various diseases in broad generations. Urinary metabolites may serve as non-invasive biomarkers of protein undernutrition; however, this requires further investigation. We aimed to identify novel urinary metabolites as biomarker candidates responsive to protein undernutrition. Adult rats were fed control (CT; 14 % casein) or isoenergetic low-protein (LP; 5 % casein) diets for 4 weeks. 1H NMR metabolomics was applied to urine, plasma and liver samples to identify metabolites responsive to protein undernutrition. Liver samples were subjected to mRNA microarray and quantitative PCR analyses to elucidate the mechanisms causing fluctuations in identified metabolites. Urinary taurine levels were significantly lower in the LP group than in the CT group at week 1 and remained constant until week 4. Hepatic taurine level and gene expression level of cysteine dioxygenase type 1 were also significantly lower in the LP group than in the CT group. Urinary trimethylamine N-oxide (TMAO) levels were significantly higher in the LP group than in the CT group at week 2 and remained constant until week 4. Hepatic TMAO level and gene expression levels of flavin-containing mono-oxygenase 1 and 5 were also significantly higher in the LP group than in the CT group. In conclusion, urinary taurine and TMAO levels substantially responded to protein undernutrition. Furthermore, changes in hepatic levels of these metabolites and gene expressions associated with their metabolic pathways were also reflected in their fluctuating urinary levels. Thus, taurine and TMAO could act as non-invasive urinary biomarker candidates to detect protein undernutrition.

Development and validation of a short food questionnaire to screen for low protein intake in community-dwelling older adults: The Protein Screener 55+ (Pro55+).

In old age, sufficient protein intake is important to preserve muscle mass and function. Around 50% of older adults (65+ y) consumes ≤1.0 g/kg adjusted body weight (BW)/day (d). There is no rapid method available to screen for low protein intake in old age. Therefore, we aimed to develop and validate a short food questionnaire to screen for low protein intake in community-dwelling older adults. We used data of 1348 older men and women (56-101 y) of the LASA study (the Netherlands) to develop the questionnaire and data of 563 older men and women (55-71 y) of the HELIUS study (the Netherlands) for external validation. In both samples, protein intake was measured by the 238-item semi-quantitative HELIUS food frequency questionnaire (FFQ). Multivariable logistic regression analysis was used to predict protein intake ≤1.0 g/kg adjusted BW/d (based on the HELIUS FFQ). Candidate predictor variables were FFQ questions on frequency and amount of intake of specific foods. In both samples, 30% had a protein intake ≤1.0 g/kg adjusted BW/d. Our final model included adjusted body weight and 10 questions on the consumption (amount on average day or frequency in 4 weeks) of: slices of bread (number); glasses of milk (number); meat with warm meal (portion size); cheese (amount and frequency); dairy products (like yoghurt) (frequency); egg(s) (frequency); pasta/noodles (frequency); fish (frequency); and nuts/peanuts (frequency). The area under the receiver operating characteristic curve (AUC) was 0.889 (95% CI 0.870-0.907). The calibration slope was 1.03 (optimal slope 1.00). At a cut-off of ≤0.8 g/kg adjusted BW/d, the AUC was 0.916 (96% CI 0.897-0.936). Applying the regression equation to the HELIUS sample, the AUC was 0.856 (95% CI 0.824-0.888) and the calibration slope 0.92. Regression coefficients were therefore subsequently shrunken by a linear factor 0.92. To conclude, the short food questionnaire (Pro55+) can be used to validly screen for protein intake ≤1.0 g/kg adjusted BW/d in community-dwelling older adults. An online version can be found at www.proteinscreener.nl. External validation in other countries is recommended.

Protein and micronutrient deficiencies in patients with radiation cystitis and outcome after hyperbaric oxygen therapy.

BACKGROUND & AIMS: Haemorrhagic radiation cystitis (HRC) is a late complication of pelvic radiotherapy. Severe cases are difficult to treat due to persistent or recurrent bleeding, despite urological and hyperbaric oxygen therapy (HBOT). However, wound healing requires a good nutritional status. In this respect, we aimed at analysing the nutritional status of patients with HRC prior to the onset of HBOT and at highlighting predictive nutritional factors of outcome. METHODS: Data were retrospectively collected from a cohort of 179 patients with HRC (between 2011 and 2015). Haematuria was graded according to the Subjective, Objective, Management, Analytic scale (SOMA): grade-4 (n = 46) was compared with grade-3 (n = 56), and with grades 1 and 2 (n = 77). S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium, and essential fatty acids were evaluated before HBOT. HBOT response was measured at 3 months according to the haematuria SOMA grade. The Mann-Whitney test, Fisher's exact test and principal-component analysis were used to compare groups. RESULTS: Patients with higher haematuria grades (3 and 4) harboured significant deficiencies in S-albumin, prealbumin, vitamins C, D and B6, zinc, selenium and essential fatty acids. Moreover, grade-4 patients without improvement after 3 months of HBOT had significant lower initial levels of S-albumin, vitamin C, selenium and linoleic acid. Vitamin C levels <2.5 mg/L were strongly associated with HBOT non-response (OR 23.14, 95% CI 3.73-143.69, p = 0.002). CONCLUSIONS: Our analyses show serious nutritional deficiencies associated with higher grades of HRC and worse prognoses. Patients with haemorrhagic cystitis might benefit from an adequate dietary supplementation to support healing of their bladder mucosa.

Slowly progressive d-bifunctional protein deficiency with survival to adulthood diagnosed by whole-exome sequencing.

d-Bifunctional protein (DBP) deficiency is an autosomal recessive disorder of peroxisomal fatty acid oxidation caused by mutations in HSD17B4. It is typically fatal by the age of two years with symptom onset during the neonatal period, and survival until late childhood is rare. We herein report the case of a patient with DBP deficiency surviving until adulthood, who showed severe sensorineural deafness, disturbances in language acquisition, slowly progressive cerebellar ataxia, and peripheral neuropathy. This patient, in whom findings of prior investigations were nondiagnostic, had been followed up as having an early-onset spinocerebellar degeneration of unknown etiology. Whole-exome sequencing analysis at the age of 36 showed two heterozygous variants in the gene HSD17B4, which encodes DBP in this patient. A panel of peroxisomal investigations showed normal levels of very long chain fatty acids (VLCFAs) in plasma and elevated serum phytanic acid levels. Recently, an increasing number of patients with DBP deficiency surviving until adolescence/adulthood have been reported, in whom abnormalities in the levels of VLCFAs and other peroxisomal metabolites are marginal or nonexistent. Genetic analysis of HSD17B4 should be considered in adult patients with cerebellar ataxia, peripheral neuropathy, and pyramidal signs in addition to sensorineural auditory disturbance since childhood.

Estudo do perfil de expressão de componentes da via de sinalização sonic hedgehog em displasia epitelial oral / Study of the expression profile of components of sonic hedgehog signaling pathway in oral epithelial dysplasia

A displasia epitelial oral (DEO) é um aspecto histológico descrito em lesões potencialmente malignas, cujos mecanismos relacionados a patogênese e potencial de transformação são pouco conhecidos. Sabendo-se que a via de sinalização Sonic Hedgehog(SHH)tem participação no desenvolvimento do carcinoma escamocelular de boca(CEB) e que as proteínas relacionadas a esta via de sinalização estão envolvidas nos mecanismos biológicos relacionados a iniciação e progressão de tumores humanos. O objetivo deste trabalho foi estudar a expressão das proteínas da via de sinalização SHH em DEO, a fim de contribuir para o conhecimento do perfil biológico desta lesão...

Oral epithelial dysplasia (OED) is a histological aspect described in premalignant lesions and themechanisms related to the pathogenesis and malignant progression are poorly understood. It is knownthat Sonic Hedgehog (SHH) signaling pathway participates in the development of oral squamous cellcarcinoma, and proteins related to this cascade are involved in biological mechanisms related to theinitiation and progression of human tumors. The aim of this study was to investigate SHH signalingmolecules in OED, in order to contribute to the knowledge of the biological profile of this lesion...

Valor prognóstico do estado nutricional na síndrome coronariana aguda / Prognostic value of nutritional status in acute coronary syndrome

Fundamentos: Sabe-se que os distúrbios nutricionais, tanto a obesidade como a desnutrição, têm importante interferência sobre a saúde, seja como fator de risco para doenças ou como agravante delas. Embora a obesidade seja um fator de risco para doença coronariana, seu impacto na síndrome coronariana aguda (SCA) não está estabelecido. Os poucos estudos encontrados apresentam resultados conflitantes. Objetivo: Investigar a relação entre o estado nutricional e a ocorrência de eventos em pacientes com SCA. Método: Estudo de coorte incluindo 171 pacientes, admitidos entre junho 2004 e outubro 2005. Os pacientes foram avaliados pelo índice de massa corporal (IMC), percentual de gordura corporal (PGC) e albumina sérica.O evento combinado (óbito, cirurgia de revascularização miocárdica, intervenção coronariana percutânea, reinfarto e angina) foi observado até a alta hospitalar. Resultados: Foram encontrados 64 pacientes sem evento e 105 com evento. No grupo com evento, 44,1 foram classificados como desnutridos segundo a albumina sérica. No grupo sem evento, 29 foram considerados desnutridos e 71 normais (p=0,05). Os pacientes com infarto agudo do miocárdio sem supradesnivelamento do segmento ST que tiveram evento apresentaram PGC (p=0,017) e IMC (p=0,035)menores que aqueles sem evento. Segundo regressão logística, apenas a albumina ≤3,5g/ foi significativa para predizer a ocorrência de evento. Conclusão: O estado nutricional interfere com a evolução dos pacientes com SCA. Tanto a albumina baixa quanto o IMC e o PGC baixos estão relacionados a maior risco de eventos em pacientes com SCA.

Influence of the timing of switching a protein-free to a protein-containing diet on the wound healing process in a rat all-layer skin defect.

We prepared full thickness skin defects in rats fed on a protein-free diet as a hypoproteinaemia model, then switched the animals to a diet containing a normal protein level 1, 6 or 12 days after wounding (inflammatory, granulation and rearrangement phases of the wound healing process) to examine whether improvement in the low-protein state promotes subsequent wound healing. The interval until wound healing in rats fed on a normal protein diet was significantly shorter, whereas that in rats continuously fed on a protein-free diet was significantly longer than those of other groups. Early correction tended to accelerate wound healing. Although wound contraction in groups receiving a protein-corrected or protein-free diet remained similar until 15 days after wounding, thereafter the duration of the rearrangement phase was significantly longer in the protein-free group than in the other groups. The collagen level per unit of granulation tissue area during wound healing was significantly lower in the protein-free group than in the other groups. These findings indicate that protein correction at any time after wounding accelerates wound healing, although early correction is more effective, and reduces the duration of the rearrangement phase more than those of the inflammatory and granulation phases because of the deposit of collagen.

Síndrome de la burbuja gástrica, o «gas bloat syndrome», en dos pacientes con patología neurológica / Gas bloat syndrome in two patients with neurological pathology

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Hierro libre, transferrina y ferritina séricas en desnutrición aguda grave / 'Free' iron, transferrin and ferritin Levels in serum and their relation with severe malnutrition

Introducción El hierro libre en suero se ha asociado con el desarrollo del edema en la desnutrición aguda grave tipo kwashiorkor. Materiales y métodos Estudio descriptivo, de corte, tipo cross-sectional, comparó 24 niños con desnutrición edematosa, 22 con marasmo y 20 sin desnutrición. Se determinó en suero: hierro libre, transferrina, índice de saturación y capacidad de fijación de hierro, ferritina, proteínas totales, albúmina, hierro total y proteína C reactiva (PCR). Resultados Se halló diferencia significativa entre los niños desnutridos que tuvieron hierro libre en suero y el grupo control en el cual no se detectó, sin embargo no hubo diferencia significativa en la concentración sérica de hierro libre entre marasmáticos y edematosos. La transferrina correlacionó negativamente con el hierro libre (r = -0,519; p = 0,000). Las proteínas totales, albúmina y transferrina fueron significativamente más bajas en los niños con edema que con marasmo. Una baja concentración de transferrina y un alto índice de saturación, podrían estimar la probabilidad del edema en un 67,5 % (p = 0,001). Conclusiones La desnutrición aguda grave se asoció con la presencia de hierro libre en suero tanto en los niños con marasmo como con edema. El hierro libre no explica la presencia de edema, pero la concomitancia de una baja concentración de transferrina y un alto índice de saturación podrían contribuir a su etiología, lo mismo que la hipoalbuminemia grave

Introduction 'Free' serum iron has been associated with the development of edema in Kwashiorkor-type severe acute malnutrition. Material and methods A descriptive, cross sectional study was performed. Twenty-four children with edematous malnutrition, 22 with marasmus and 20 without malnutrition were compared. 'Free' iron, transferrin, saturation index and attachment capacity of iron, ferritin, total protein, albumin, total iron, and C-reactive protein (CRP) were determined in serum. Results A significant difference was found between malnourished children with 'free' serum iron and the control group in which 'free' iron was not found. However, no significant differences were found in 'free' serum iron levels between marasmatic and edematous children. Transferrin was negatively correlated with 'free' iron (r = -0.519; p = 0.000). Total proteins, albumin and transferrin were all significantly lower in children with edema than in those with marasmus. A low transferrin level and a high saturation index could be used to estimate the probability of edema in 67.5 % of cases (p = 0.001). Conclusions Severe acute malnutrition was associated with the presence of 'free' serum iron both in children with marasmus and in those with edema. 'Free' iron does not explain the presence of edema but, as with severe hypoalbuminemia, the concurrence of a low transferrin level and a high saturation index may contribute to the etiology of edema

Bacteriemia por Pantoea agglomerans / Bacteremia caused by Pantoea agglomerans

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Enfermedad de Buerger (tromboangeítis obliterante) / Buerger´s disease (thromboangiitis obliterans)

La tromboangeítis obliterante es una enfermedad segmentaria, inflamatoria y oclusiva, que afecta de forma predominante a las arterias y venas de mediano y pequeño calibre de las extremidades. Ocurre con mayor frecuencia en varones jóvenes fumadores, sobre todo de países mediterráneos y asiáticos. Se considera un proceso autoinmune en relación con el tabaco. Clínicamente, se caracteriza por la presencia de lesiones isquémicas digitales dolorosas. En el estudio histopatológico, suele verse un trombo oclusivo intraluminal con un infiltrado inflamatorio de predominio agudo. Para realizar el diagnóstico es importante excluir otras causas de isquemia de las extremidades y diversos autores han propuesto criterios para establecer dicho diagnóstico. El tratamiento sólo es eficaz si va acompañado de la abstención del tabaco. Además, existen diversas estrategias farmacológicas y quirúrgicas para su manejo

Thromboangiitis obliterans (TAO) is a segmental, inflammatory, vasooclusive disease that predominantly affects the small and medium sized arteries and veins of the extremities. It most often occurs in young male smokers, especially those from Mediterranean and Asian countries. It is considered ana autoimmune process related to the use of tobacco products. Clinically, it is characterized by the presence of painful, ischemic ulcers of the digits. Histopathological studies usually show an occlusive intraluminal thrombus with a predominantly acute inflammatory infiltrate. To make the diagnosis, it is important to exclude other causes of ischemia of the extremities, and different authors have proposed criteria to establish this diagnosis. Treatment is only effective if it is accompanied by abstention from tobacco. There are aldo different pharmacological and surgical strategies for its management

Prevalencia de desnutrición en pacientes ingresados en un hospital de rehabilitación y traumatología / Malnutrition prevalence in patients admitted to a rehabilitation and orthopedic surgery hospital

Objetivo: Diferentes estudios ponen de manifiesto la escasa atención concedida al estado nutricional en la historia y práctica clínica, lo que determina el desconocimiento del estado nutricional del paciente a su ingreso en el hospital y por tanto la imposibilidad de prevenir la malnutrición hospitalaria. El objetivo de nuestro estudio ha sido determinar la prevalencia de desnutrición de pacientes ingresados en un Hospital de Traumatología y Rehabilitación. Métodos: Estudio observacional analítico en 250 pacientes (60% hombres y 40% mujeres) seleccionados aleatoriamente, a los que se realizó una evaluación nutricional al ingreso hospitalario, mediante antropometría (Peso, talla, IMC, PB, PCT, PCSA y PCSE) y pruebas bioquímicas (Albúmina, Prealbúmina y Transferrina). Resultados: Según el IMC la prevalencia de desnutrición fue del 8%, el promedio de desnutrición de tipo calórico fue del 2,8% (según antropometría) y la prevalencia de desnutrición proteica se eleva al 54,8% (según marcadores bioquímicos). Conclusiones: La elevada prevalencia de malnutrición proteica o visceral (54,8%) demostrada en este estudio, pone de manifiesto la importancia de determinar el estado nutricional al ingreso hospitalario, particularmente en los pacientes de tipo quirúrgico, como es el caso de la mayoría de los que ingresan en los hospitales traumatológicos (AU)

Objective: Different studies show the scarce attention granted to the nutritional state in historical and clinical practice, what determines the ignorance of the patient's nutritional status to their entrance in the hospital and, therefore, the impossibility to prevent the hospital malnutrition. The objective of our study has been to determine the prevalence of patients' malnutrition entered in a Hospital of Orthopedic surgery and Rehabilitation. Methods: Observational and analytical study in 250 randomized patients (60% men and 40% women), who were nutritionally evaluated when entering, the hospital, by means of anthropometry (Weigh, height, BMI, skinfold, corporal circumferences) and biochemical tests (Albumin, Prealbumin and Transferrin). Results: According to the BMI the prevalence of malnutrition was of 8%, the average of caloric malnutrition was of 2,8% (according to anthropometry) and the prevalence of many-sided malnutrition rises to 54,8% (according to biochemical markers). Conclusions: The high prevalence of fundamental malnutrition (54,8%) demonstrated in this study, it shows the importance of determining the nutritional status when entering the hospital, particularly surgical type' patiens as is the case of most of those who enter the Orthopedic surgery hospitals (AU)

Respuesta a la alimentación enteral en pacientes con diferentes grados de catabolismo proteico / Response to enteral feeding in patients with different degrees of protein catabolism

El objetivo de este trabajo es valorar a través del balance nitrogenado, la utilización de los nutrientes por vía enteral y el aporte óptimo calórico-proteico requeridoen pacientes con diferentes grados de catabolismo. La respuesta a la alimentación enteral en estos pacientes, evaluada a través de la excreción urinaria de urea, demustra que los grupos con catabolismo moderado y severo se benefician parcialmente con el aporte de nutrientes, lográndose un retardo de la desnutrición proteica con aportes que no superen 1g de N2/kg de peso teórico, mientras los pacientes del grupo A se encuentran en una situación ideal para recuperar la masa orgánica beneficiándose con aportes calórico-proteicos más elevados(AU)