Redefining migraine prevention: early treatment with anti-CGRP monoclonal antibodies enhances response in the real world.

BACKGROUND: Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months. METHODS: European multicentre, prospective, real-world study, including high-frequency episodic or chronic migraine (CM) patients treated since March 2018 with anti-CGRP MAbs. We defined good and excellent responses as ≥50% and ≥75% reduction in monthly headache days (MHD) at 6 months, respectively. Generalised mixed-effect regression models (GLMMs) were used to identify variables independently associated with treatment response. RESULTS: Of the 5818 included patients, 82.3% were females and the median age was 48.0 (40.0-55.0) years. At baseline, the median of MHD was 20.0 (14.0-28.0) days/months and 72.2% had a diagnosis of CM. At 6 months (n=4963), 56.5% (2804/4963) were good responders and 26.7% (1324/4963) were excellent responders. In the GLMM model, older age (1.08 (95% CI 1.02 to 1.15), p=0.016), the presence of unilateral pain (1.39 (95% CI 1.21 to 1.60), p<0.001), the absence of depression (0.840 (95% CI 0.731 to 0.966), p=0.014), less monthly migraine days (0.923 (95% CI 0.862 to 0.989), p=0.023) and lower Migraine Disability Assessment at baseline (0.874 (95% CI 0.819 to 0.932), p<0.001) were predictors of good response (AUC of 0.648 (95% CI 0.616 to 0.680)). These variables were also significant predictors of excellent response (AUC of 0.691 (95% CI 0.651 to 0.731)). Sex was not significant in the GLMM models. CONCLUSIONS: This is the largest real-world study of migraine patients treated with anti-CGRP MAbs. It provides evidence that higher migraine frequency and greater disability at baseline reduce the likelihood of responding to anti-CGRP MAbs, informing physicians and policy-makers on the need for an earlier treatment in order to offer the best chance of treatment success.

Plant-Based Diets and Risk of Multimorbidity: The Health and Retirement Study.

BACKGROUND: Plant-based diets have gained attention due to their beneficial effects against major chronic diseases, although their association with multimorbidity is mostly unknown. OBJECTIVES: We examined the association between the healthful (hPDI) and unhealthful plant-based diet indices (uPDI) with multimorbidity among middle-aged and older adults from the United States. METHODS: Data on 4262 adults aged >50 y was obtained from the 2012-2020 Health and Retirement Study (HRS) and 2013 Health Care and Nutrition Study (HCNS). Food consumption was collected at baseline with a food frequency questionnaire and 2 PDIs were derived: the hPDI, with positive scores for healthy plant foods and reverse scores for less healthy plant foods and animal foods; and the uPDI, with only positive scoring for less healthy plant foods. Complex multimorbidity, defined as ≥3 coexistent conditions, was ascertained from 8 self-reported conditions: hypertension, diabetes, cancer, chronic lung disease, heart disease, stroke, arthritis, and depression. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: After a median follow-up of 7.8 y, we documented 1202 incident cases of multimorbidity. Compared with the lowest quartile, higher adherence to the hPDI was inversely associated with multimorbidity (HR for quartile 3: 0.77; 95% CI: 0.62, 0.96 and HR for quartile 4: 0.79; 95% CI, 0.63, 0.98; P-trend = 0.02). In addition, a 10-point increment in the hPDI was associated with a 11% lower incidence of multimorbidity (95% CI: 1, 20%). No significant associations were found for the uPDI after adjusting for sociodemographic and lifestyle factors. CONCLUSIONS: Higher adherence to the hPDI was inversely associated with multimorbidity among middle-aged and older adults. Plant-based diets that emphasize consumption of high-quality plant foods may help prevent the development of complex multimorbidity.

Distribution of daily protein intake across meals and all-cause mortality in community-dwelling older adults.

Recent findings suggest that the distribution of protein intake throughout the day has an impact on various health outcomes in older adults, independently of the amount consumed. We evaluated the association between the distribution of dietary protein intake across meals and all-cause mortality in community-dwelling older adults. Data from 3225 older adults aged ≥ 60 years from the Seniors-ENRICA-1 cohort were examined. Habitual dietary protein consumption was collected in 2008-2010 and in 2012 through a validated diet history. Protein distribution across meals was calculated for each participant as the coefficient of variation (CV) of protein intake per meal, in sex-specific tertiles. Vital status was obtained from the National Death Index up to 30 January 2020. Cox proportional hazards regression was performed to determine the hazard ratios (HR) and their 95 % CI for the association between the distribution of daily protein intake across meals and all-cause mortality. Over a median follow-up of 10·6 years, 591 deaths occurred. After adjustment for potential confounders, the CV of total protein intake was not associated with all-cause mortality (HR and 95 % CI in the second and third tertile v. the lowest tertile: 0·94 (0·77, 1·15) and 0·88 (0·72, 1·08); Ptrend = 0·22). Similarly, the HR of all-cause mortality when comparing extreme tertiles of CV for types of protein were 0·89 (0·73, 1·10) for animal-protein intake and 1·02 (0·82, 1·25) for plant-protein intake. Dietary protein distribution across meals was not associated with all-cause mortality, regardless of protein source and amount, among older adults. Further studies should investigate whether this picture holds for specific causes of death.

Duration and Quality of Sleep and Risk of Self-reported Hearing Loss: The UK Biobank Study.

OBJECTIVE: The duration and quality of sleep have been associated with multiple health conditions in adults. However, whether sleep duration and quality are associated with hearing loss (HL) is uncertain. The present study investigates the prospective association between duration and quality of sleep and HL. DESIGN: This longitudinal analysis included 231,650 participants aged 38 to 72 years from the UK Biobank cohort, established in 2006-2010 in the United Kingdom. Duration and sleep complaints (snoring at night, daytime sleepiness, sleeplessness, difficulty getting up in the morning, and eveningness preference) were self-reported. HL was self-reported at baseline and during the follow-up. RESULTS: Over a median follow-up of 4.19 (SD: 2.15) years, 6436 participants reported incident HL. In fully adjusted models, in comparison with sleeping between 7 and 8 hours a day, the adjusted hazard ratio (HR) (95% CI) associated with sleeping <7 hours a day was 1.01 (0.95 to 1.07), and for sleeping >8 hours a day was 0.98 (0.88 to 1.08). After adjustment for potential confounders, the HRs (95% confidence interval) of HL associated with having 1, 2, 3, and 4 to 5 vs. 0 sleep complaints were: 1.15 (1.05 to 1.27), 1.16 (1.05 to 1.28), 1.32 (1.19 to 1.47), and 1.49 (1.31 to 1.69), respectively; p for trend: <0.001. An increase in the number of sleep complaints was associated with higher risk of HL among participants with non-optimal sleep duration than among participants with optimal sleep duration. CONCLUSION: In this large population-based study, poor sleep quality was associated with an increased risk of HL; however, sleep duration was not associated with risk.

Multimorbidity Patterns in Older Adults: the Role of Social Variables and Lifestyle Behaviors.

INTRODUCTION: While some condition clusters represent the chance co-occurrence of common individual conditions, others may represent shared causal factors. The aims of this study were to identify multimorbidity patterns in older adults and to explore the relationship between social variables, lifestyle behaviors, and the multimorbidity patterns identified. METHODS: This was a cross-sectional design. Data came from 3,273 individuals aged ≥65 from the Seniors-ENRICA-2 cohort; information on 60 chronic disease categories, categorized according to the 2nd edition of the International Classification of Primary Care and the 10th edition of the International Classification of Diseases, was obtained from clinical record linkage. To identify multimorbidity patterns, an exploratory factor analysis was conducted over chronic disease categories with a prevalence >5%, using Oblimin rotation and Kaiser's eigenvalues-greater-than-one rule. The association between multimorbidity patterns and their potential determinants was assessed with multivariable linear regression. RESULTS: The three-factor solution (Musculoskeletal diseases and mental disorders, Cardiometabolic diseases, and Cardiopulmonary diseases) explained 64.5% of the total variance. Being older, lower occupational category, higher levels of loneliness, lower levels of physical activity, and higher body mass index were associated with higher scores in the multimorbidity patterns identified. Female sex was linked to the Musculoskeletal diseases and mental disorders pattern, while being male was revealed to the two remaining multimorbidity patterns. A high diet quality was inversely related to Cardiometabolic diseases, while optimal sleep duration was inversely related to Cardiopulmonary diseases. CONCLUSION: Three multimorbidity patterns were identified in older adults. Multimorbidity patterns were differently associated with social variables and lifestyles behavioral factors.

Dietary fat intake and risk of disabling hearing impairment: a prospective population-based cohort study.

PURPOSE: To examine the associations of specific dietary fats with the risk of disabling hearing impairment in the UK Biobank study. METHODS: This cohort study investigated 105,592 participants (47,308 men and 58,284 women) aged ≥ 40 years. Participants completed a minimum of one valid 24-h recall (Oxford Web-Q). Dietary intake of total fatty acids, polyunsaturated fatty acids (PUFA), saturated fatty acids (SFA), and monounsaturated fatty acids (MUFA) was assessed at baseline. Functional auditory capacity was measured with a digit triplet test (DTT), and disabling hearing impairment was defined as a speech reception threshold in noise > - 3.5 dB in any physical exam performed during the follow-up. RESULTS: Over a median follow-up of 3.2 (SD: 2.1) years, 832 men and 872 women developed disabling hearing impairment. After adjustment for potential confounders, including lifestyles, exposure to high-intensity sounds, ototoxic medication and comorbidity, the hazard ratios (HRs), and 95% confidence interval (CI) of disabling hearing function, comparing extreme quintiles of intakes were 0.91 (0.71-1.17) for total fat, 1.09 (0.83-1.44) for PUFA, 0.85 (0.64-1.13) for SFA and 1.01 (0.74-1.36) for MUFA among men. Among women, HRs comparing extreme intakes were 0.98 (0.78-1.24) for total fat, 0.69 (0.53-0.91) for PUFA, 1.26 (0.96-1.65) for SFA, and 0.91 (0.68-1.23) for MUFA. Replacing 5% of energy intake from SFA with an equivalent energy from PUFA was associated with 25% risk reduction (HR: 0.75; 95% CI: 0.74-0.77) among women. CONCLUSIONS: PUFA intake was associated with decreased risk of disabling hearing function in women, but not in men.

Prospective association between dietary magnesium intake and physical performance in older women and men.

PURPOSE: Magnesium is a profuse intracellular cation with a key role in muscle function and cellular senescence. The aim was to examine the prospective association between 5 year changes in dietary intake of magnesium and changes in physical performance among older men and women. METHODS: Prospective study conducted over 863 community-dwellers aged ≥ 65 years from the Seniors-ENRICA cohort (Spain). In 2012 and 2017, a validated computerized face-to-face diet history was used to record the consumption of up to 880 foods. From these data, we estimated changes in dietary magnesium intake. The Short Physical Performance Battery (SPPB) was also conducted in both time points and we obtained changes in the score during follow-up, with positive values indicating physical performance improvement. RESULTS: Over 5 years of follow-up, an increase in magnesium intake was associated with an increment in the SPPB score among older women [multivariate ß (95% confidence interval): 1.01 (0.49; 1.52), p-trend: 0.001]. In addition, changes from non-adherence to adherence to both estimated average requirement and recommended dietary allowance during follow-up period were associated with an increment in SPPB score among older women [1.14 (0.36; 1.92) and 0.84 (0.22; 1.47), respectively]. No significant associations between changes in magnesium intake and changes in SPPB score were observed in men. CONCLUSIONS: Both increase of magnesium intake and change from non-adherence to adherence to dietary reference magnesium intake was prospectively associated with better physical performance among older women, but not among men.

Diet Quality and the Risk of Impaired Speech Reception Threshold in Noise: The UK Biobank cohort.

OBJECTIVE: Previous studies have examined the association between several diet quality indexes and risk of hearing loss, based on self-reported information or on audiometry test, with inconsistent results. However, the impact of healthy diets on the capacity to listening in noise, a proxy of disability due to hearing loss, is unknown. This research assessed the prospective association between five diet quality indexes and the speech reception threshold in noise in the UK Biobank study. DESIGN: Prospective cohort with 105,592 participants aged ≥40 years. At baseline, adherence to the Mediterranean Diet Adherence Screener, the alternate Mediterranean Diet score, the Dietary Approaches to Stop Hypertension, the Alternate Healthy Eating Index-2010, and the healthful Plant-Based Diet Index were assessed. Functional auditory capacity was measured with a digit triplet test, and impairment was defined as a speech reception threshold in noise >-3.5 dB in any physical exam during the follow-up. RESULTS: Over a median follow-up of 3.2 (SD: 2.1) years, 1704 participants showed impaired speech reception threshold in noise. After adjusting for potential confounders, the hazard ratios (95% confidence interval) of impairment per 1-SD increase in the Mediterranean Diet Adherence Screener, alternate Mediterranean Diet score, Dietary Approaches to Stop Hypertension, Alternate Healthy Eating Index-2010 and healthful Plant-Based Diet Index scores were, respectively, 0.98 (0.94 to 1.03), 1.01 (0.96 to 1.06), 1.02 (0.97 to 1.07), 1.01 (0.96 to 1.06), and 1.00 (0.96 to 1.05). Results were similar when analyses were restricted to those >60 years, with British ethnicity, without chronic disease, without tinnitus or with optimal cognitive function. CONCLUSIONS: Adherence to a healthy diet did not show an association with the speech reception threshold in noise. More research is needed to identify the impact of individual foods or nutrients on this outcome.

Plasma Amino Acids and Risk of Impaired Lower-Extremity Function and Role of Dietary Intake: A Nested Case-Control Study in Older Adults.

INTRODUCTION: Amino acids are key elements in the regulation of the aging process which entails a progressive loss of muscle mass. The health effects of plasma amino acids can be influenced by dietary intake. This study assessed the prospective association between amino acid species and impaired lower-extremity function (ILEF) in older adults, exploring the role of diet on this association. METHODS: This is a case-control design comprising 43 incident cases of ILEF and 85 age- and sex-matched controls. Plasma concentrations of 20 amino acid species were measured at baseline using liquid chromatography-tandem mass spectrometry, and incident cases of ILEF were measured after 2 years by means of the Short Physical Performance Battery. Conditional logistic regression models were used to assess longitudinal relationships. RESULTS: After adjusting for potential confounders, higher levels of tryptophan were associated with a decreased 2-year risk of ILEF (OR per 1-SD increase = 0.64, 95% CI = [0.42, 0.97]), while glutamine and total essential amino acids were linked to higher ILEF risk (OR = 1.57, 95% CI = [1.01, 2.45]; OR = 1.89, 95% CI = [1.18, 3.03], respectively). Those with a lower adherence to a Mediterranean diet, a higher BMI, a higher consumption of red meat, and a lower consumption of nuts and legumes had an increased risk of ILEF associated with higher levels of essential amino acids. DISCUSSION/CONCLUSION: Some amino acid species could serve as risk markers for physical function decline in older adults, and healthy diet might attenuate the excess risk of ILEF linked to essential amino acids.

Late-life disability trajectories in Yoruba Nigerians and the Spanish population: a state space model in continuous time.

OBJECTIVES: We compared the trajectory of activities of daily living (ADL) in a nationally representative sample of older Nigerians with their Spanish peers and identified factors to explain country-specific growth models. METHODS: Data from two household multistage probability samples were used, comprising older adults from Spain (n = 2,011) and Nigeria (n = 1,704). All participants underwent assessment for ADL. Risk factors including sex, household income, urbanicity, years of education, depression, alcohol consumption and smoking were assessed using validated methods. State-space model in continuous time (SSM-CT) methods were used for trajectory comparison. RESULTS: Compared with Nigerians (µADL80=0.44, SE = 0.015, p < 0.001), Spanish older adults had higher disability scores (µADL80=1.23, SE = 0.021, p < 0.001). In SSM-CT models, the rate of increase in disability was faster in Nigerians (Nigeria: ß = 0.061, p<.01; Spain: ß = 0.028, p < 0.010). An increasing course of disability in the Spanish sample was predicted by female sex, lower education and depression diagnosis. CONCLUSION: The rate of increase in disability was faster in older Nigerians living in an economically disadvantaged context.

Prolonged nightly fasting and lower-extremity functioning in community-dwelling older adults.

It is unknown if time-restricted feeding confers a protective effect on the physical function of older adults. The aim of this study was to assess prolonged nightly fasting in association with performance-based lower-extremity function (LEF) in a large population of community-dwelling older adults. A cross-sectional study was carried out among 1226 individuals ≥64 years from the Seniors-ENRICA-II (Study on Nutrition and Cardiovascular Risk in Spain) cohort. Habitual diet was assessed through a validated diet history. Fasting time was classified into the following categories: ≤9, 10-11 and ≥12 h/d (prolonged nightly fasting). Performance-based LEF was assessed with the Short Physical Performance Battery (SPPB). After adjusting for potential confounders, a longer fasting period was associated with a higher likelihood of impaired LEF (OR for the second and third categories v. ≤ 9 h/d fasting: 2·27 (95 % CI 1·56, 3·33) and 2·70 (95 % CI 1·80, 4·04), respectively; Ptrend < 0·001). Fasting time showed a significant association with the SPPB subtests balance impairment (OR for highest v. shortest fasting time: 2.48; 95 % CI 1·51, 4·08; Ptrend = 0·001) and difficulty to rise from a chair (OR 1·47; 95 % CI 1·05, 2·06; Ptrend = 0·01). The risk associated with ≥12 h fasting among those with the lowest levels of physical activity was three times higher than among those with ≤9 h fasting with the same low level of physical activity. Prolonged nightly fasting was associated with a higher likelihood of impaired LEF, balance impairment, and difficulty to rise from a chair in older adults, especially among those with low levels of physical activity.

Effects of transient and chronic loneliness on major depression in older adults: A longitudinal study.

OBJECTIVES: The number of older adults is rapidly rising globally. Loneliness is a common problem that can deteriorate health. The aims of this work were to identify different types of loneliness (transient and chronic) and to assess their association with depression over time. METHODS: A nationally representative sample from the Spanish population comprising 1190 individuals aged 50+ years was interviewed on three evaluations over a 7-year period. The UCLA Loneliness Scale was used to measure loneliness. While chronic loneliness was defined as the presence of loneliness across all three waves, transient loneliness expressed the presence of loneliness in one wave only. A 12-month major depressive episode was assessed at each interview. After confirming the cross-sectional relationship, a multilevel mixed-effects model was used to examine the association between loneliness and depression. RESULTS: Almost a quarter of individuals felt lonely and one out of 10 presented depression at baseline. Of the sample, 22.78% showed transient loneliness, while 6.72% presented the chronic type. People experiencing chronic loneliness were at a higher risk of presenting major depression (OR = 6.11; 95% CI = 2.62, 14.22) than those presenting transient loneliness (OR = 2.22; 95% CI = 1.19, 4.14). This association varied over time and was stronger at the first follow-up than at the second one. CONCLUSIONS: Focusing on loneliness prevention could reduce the risk of depression. Chronic loneliness is a public health problem that should be addressed through the full participation of the political, social, and medical sectors.

Are legume-based recipes an appropriate source of nutrients for healthy ageing? A prospective cohort study.

Although legumes are rich in protein and fibre, and low in saturated fat and Na, traditional legume-based recipes include substantial amounts of processed meat, salt and potatoes, which could counteract the potential benefits of legumes. This prospective study aimed to assess the longitudinal association of consumption of different types of legumes, and traditional legume-based recipes, with unhealthy ageing in older adults. Data were taken from 2505 individuals aged ≥60 years from the Seniors-ENRICA cohort. Habitual legume consumption was assessed in 2008-2010 with a validated diet history. Unhealthy ageing was measured in the 2013, 2015 and 2017 follow-up waves, with a fifty-two-item multidimensional health deficit accumulation index (DAI) which ranges from 0 (best) to 100 (worst health). The mean age was 68·7 years, with 53·1 % of women. Among study participants, 78·4 % reported consumption of legumes, with a mean intake of 57·9 g/d. Multivariable-adjusted linear regression models did not show an association between total legume consumption and the DAI over a 7-year follow-up (non-standardised coefficient for the second and highest v. the lowest tertile of consumption: 0·94 (95 % CI -0·30, 2·17) and 0·18 (95 % CI -1·07, 1·43), respectively; Ptrend = 0·35). Similar results were observed for the 3-year and 5-year follow-ups and, separately, for lentils, beans, chickpeas and traditional legume-based recipes. According to the results obtained, consumption of legumes and traditional legume-based recipes is not associated with unhealthy ageing and can be part of a healthy diet in old age.

Cross-cultural comparison of symptom networks in late-life major depressive disorder: Yoruba Africans and the Spanish Population.

BACKGROUND: The concept of European psychologisation of depression versus somatisation in non-European populations has been the basis of several studies of cultural psychopathology in the general population. Little is currently known about cross-cultural differences and similarities in late-life depression symptom reporting. We cross-culturally compared symptom reporting in the context of Major Depressive Disorder (MDD) among community-dwelling older adults from Spain and Nigeria. METHODS: We relied on data from two household multistage probability samples comprising 3,715 persons aged 65 years or older in the Spanish and Nigerian populations. All participants underwent assessments for MDD using the World Mental Health Survey version of the Composite International Diagnostic Interview. Cross-cultural comparison of broad somatic and psychological categories as well as relationship and influence of individual symptoms were analysed using the Symptom Network Analysis approach. RESULTS: Current MDD was diagnosed in 232 and 195 older persons from Spain and Nigeria, respectively. The symptom network of the two samples were invariant in terms of global strength, S(GSPAIN , GNIGERIA ) = 7.56, P = .06, with psychological and somatic symptoms demonstrating centrality in both countries. However, country-specific relationships and influence of individual symptoms were found in the network structure of both samples, M(GSPAIN , GNIGERIA ) = 2.95, P < .01. CONCLUSION: Broad somatic and psychological symptoms categories contributed to the structural network of older Africans and their peers from the Spanish population. Variations in the relationship and influence of individual symptoms suggests that the functional and "communicative" role of individual symptoms may be differentiated by context specific imperatives. J Am Geriatr Soc 68:-, 2020.

Relationship between subjective well-being and healthy lifestyle behaviours in older adults: a longitudinal study.

Objectives: People who report better subjective well-being tend to be healthier in their daily behaviours. The objective of this study is to assess whether different components of subjective well-being are prospectively associated with different healthy lifestyle behaviours and to assess whether these associations differ by age.Method: A total of 1,892 participants aged 50+ living in Spain were interviewed in 2011-12 and 2014-15. Life satisfaction was measured with the Cantril Self-Anchoring Striving Scale. Positive and negative affect were assessed using the Day Reconstruction Method. Physical activity was assessed with the Global Physical Activity Questionnaire version 2. The remaining healthy lifestyle behaviours were self-reported. Generalised Estimating Equations (GEE) models were run.Results: Not having a heavy episodic alcohol drinking was the healthy lifestyle behaviour most fulfilled (97.97%), whereas the intake of five or more fruits and vegetables was the least followed (33.12%). GEE models conducted over the 50-64 and the 65+ age groups showed that a higher life satisfaction was significantly related to a higher physical activity in both groups. Relationships between a higher negative affect and presenting a lower level of physical activity, and a higher positive affect and following the right consumption of fruits and vegetables and being a non-daily smoker, were only found in the older group.Conclusion: The relationship between subjective well-being and healthy lifestyle behaviours was found fundamentally in those aged 65+ years. Interventions focused on incrementing subjective well-being would have an impact on keeping a healthy lifestyle and, therefore, on reducing morbidity and mortality.

From Inflammation to the Onset of Fibrosis through A2A Receptors in Kidneys from Deceased Donors.

Pretransplant graft inflammation could be involved in the worse prognosis of deceased donor (DD) kidney transplants. A2A adenosine receptor (A2AR) can stimulate anti-inflammatory M2 macrophages, leading to fibrosis if injury and inflammation persist. Pre-implantation biopsies of kidney donors (47 DD and 21 living donors (LD)) were used to analyze expression levels and activated intracellular pathways related to inflammatory and pro-fibrotic processes. A2AR expression and PKA pathway were enhanced in DD kidneys. A2AR gene expression correlated with TGF-ß1 and other profibrotic markers, as well as CD163, C/EBPß, and Col1A1, which are highly expressed in DD kidneys. TNF-α mRNA levels correlated with profibrotic and anti-inflammatory factors such as TGF-ß1 and A2AR. Experiments with THP-1 cells point to the involvement of the TNF-α/NF-κB pathway in the up-regulation of A2AR, which induces the M2 phenotype increasing CD163 and TGF-ß1 expression. In DD kidneys, the TNF-α/NF-κB pathway could be involved in the increase of A2AR expression, which would activate the PKA-CREB axis, inducing the macrophage M2 phenotype, TGF-ß1 production, and ultimately, fibrosis. Thus, in inflamed DD kidneys, an increase in A2AR expression is associated with the onset of fibrosis, which may contribute to graft dysfunction and prognostic differences between DD and LD transplants.

Familial dysphagia: eosinophilic esophagitis.

We present a family with several cases of eosinophilic esophagitis. Some cases of eosinophilic esophagitis in the same family have been previously described. Patients with eosinophilic esophagitis present frequently atopy, and atopy has a strong family association due to complex interactions between genetic and environment. However, eosinophilic esophagitis has a stronger genetic component than other atopic diseases. Eosinophilic esophagitis has been linked to variations in genes like eotaxin-3, TSLP and its receptor and CAPN14, although the inheritance pattern has not yet well defined.

Enteroscopic diagnosis of intestinal malabsorption of a rare etiology: diaphragm disease.

We present the case of a 59-year-old patient with malabsorption syndrome which started with polyneuropathy. Capsule endoscopy and enteroscopy show villous denudation. Histological study confirms diaphragm disease of the small bowel. Diaphragm disease is a rare disease characterized by the presence of multiple thin diaphragms, such as septa, that narrow the intestinal lumen. The clinical features can be iron deficiency anemia, intestinal obstruction, change in bowel habits or acute abdomen secondary to perforation. It is usually generally with sustained use of high doses of non-steroidal anti-inflammatory drugs. The diagnosis usually requires the use of a capsule endoscopy or enteroscopy with biopsies.

Invasive aspergillosis of gastrointestinal debut without apparent respiratory involvement in an immunocompetent host.

A 72-year-old female presented with abdominal pain and constipation and intestinal dilation was found. Abdominal computed tomography showed two areas of thickening and stenosis in the proximal jejunum and preterminal ileum, with an unknown etiology. Exploratory laparotomy was proposed but the patient suffered a sudden and progressive decrease in consciousness. Cranial computed tomography showed an ischemic area and a midline shift. Brain biopsies suggested infection by Aspergillus Fumigatus. Despite antifungal drugs, the patient had a progressive clinical deterioration and died. The autopsy concluded a systemic infection due to Aspergillus Fumigatus. Invasive aspergillosis is a serious fungal infection and usually occurs in immunocompromised patients. It mainly affects the lungs, followed by the gastrointestinal tract. The most frequent location in gastrointestinal involvement is the small bowel. Gastrointestinal involvement is more frequent in invasive disease. Although, there are case reports of isolated gastrointestinal aspergillosis, even in immunocompetent patients without risk factors. The prognosis is poor.

Enteroscopy in the diagnosis of melanoma metastases.

We present abdominal computed tomography and enteroscopy images of a 48-year-old male patient with a previous melanoma who presented with epigastric pain. The pain was not controlled with medical management. Abdominal computed tomography and a histological study of biopsies form enteroscopy confirmed the diagnosis of metastatic melanoma. The gastrointestinal involvement of melanoma is usually metastatic. Symptomatic gastrointestinal involvement occurs in less than 5% of melanomas, although postmortem analyses have reported up to 70%. The clinical presentation is variable and usually presents as abdominal pain. The diagnosis of small intestinal involvement of melanoma is a challenge due to its poor accessibility. The enteroscopy has a fundamental role as it allows a direct visualization and biopsies to be taken for histological study.