Prevalence and characteristics of anemia in patients with diabetes mellitus aged 50 or older in health unit area of Cadiz (Spain).

BACKGROUND: Anemia is a common comorbidity in patients with diabetes mellitus (DM), particularly in older adults. However, there is a lack of data on the prevalence and the characteristics of anemia in this population in Spain. OBJECTIVE: To describe the prevalence and the characteristics of anemia in patients with DM aged 50 or older (PDM50) in a healthcare district in the province of Cádiz. METHODS: A retrospective cross-sectional study was conducted that included outpatient's laboratory tests (OLT) performed over 30 months at PDM50. RESULTS: The prevalence of anemia was 29.9% (95% CI: 28.7%-31.1%), predominating in women (33.3% vs 26.7%; P < .01), in older people stratified by decades (61.7% in 9th decade vs 12% in 5th decade; P < .01), and in those with kidney disease (44.7% vs 28%; P < .01). Most cases were mild (68.3%), normocytic (78.7%), and hypochromic (52%). Similarly, moderate-to-severe anemia was more frequent in women (39% vs 23%), their prevalence increased with age (45% in the 9th decade vs 24% in the 5th decade), and with the progression of kidney damage, either measured by a decreased glomerular filtration rate (GFR) (49% in G4 vs 25% in G1), or the presence of albuminuria (P < .01). No association was found between DM control, based on glycated hemoglobin (HbA1c), and anemia in either sex (P = .887). CONCLUSION: This study describes a high prevalence of anemia in PDM50, particularly in women, in the most advantageous people and in the presence of kidney disease, even in early stages, highlighting the clinical importance of this coexistence.

Is the use of the new Chronic Kidney Disease Epidemiology Consortium (CKD-EPI 2021) formula appropriate for the Spanish population?

INTRODUCTION: United States nephrology societies recommend changing from the CKD-EPI 2009 equation to the new CKD-EPI 2021 equation, which does not include the race coefficient, for calculating estimated glomerular filtration rate (eGFR). It is unknown how this change might affect the distribution of kidney disease in the predominantly Caucasian Spanish population. METHODS: Two databases of adults from the province of Cádiz, DB-SIDICA (N=264,217) and DB-PANDEMIA (N=64,217), that had plasma creatinine measurements recorded between 2017 and 2021 were studied. Changes in eGFR and the consequent reclassification into different categories of the KDIGO 2012 classification resulting from substituting the CKD-EPI 2009 equation for the 2021 equation were calculated. RESULTS: Compared to the 2009 equation, CKD-EPI 2021 yielded a higher eGFR, with a median of 3.8mL/min/1.73m2 (IQR 2.98-4.48) in DB-SIDICA and 3.89mL/min/1.73m2 (IQR 3.05-4.55) in DB-PANDEMIA. The first consequence was that 15.3% of the total population in DB-SIDICA and 15.1% of the total population in DB-PANDEMIA were reclassified into a higher category of eGFR, as were 28.1% and 27.3%, respectively, of the population with CKD (G3-G5); no subjects were classified into the more severe category. The second consequence was that the prevalence of kidney disease decreased from 9% to 7.5% in both cohorts. CONCLUSIONS: Implementing the CKD-EPI 2021 equation in the Spanish population, which is predominantly Caucasian, would increase eGFR by a modest amount (greater in men and those who are older or have a higher GFR). A significant proportion of the population would be classified into a higher eGFR category, with a consequent decrease in the prevalence of kidney disease.

Women's leadership in clinical research: A retrospective observational study over two decades in Spain.

BACKGROUND AND OBJECTIVE: Available data support differences by gender in the leadership of clinical investigations (CI). This study analyzes to what extent women lead these investigations. MATERIALS AND METHODS: Observational-retrospective study in a tertiary university hospital associated with one of the most important health research institutes in Spain. We analyzed the principal investigators (PI) by gender from 2001 to 2020. MAIN OUTCOME: proportion of CI led by female doctors (FD) during the study period. SECONDARY OUTCOMES: differences in PI by gender according to the type of study: clinical trials (CT) or non-interventional-researches (NIR) and according to type of funding. DATA SOURCES: Research Ethics Committee (REC) and Human Resources Department registries. RESULTS: During the study, the REC approved 8466 protocols, 52% (4408/8466) were EC, the rest were NIR. Women led 39.7% (3360/8466) of the total. The gender gap was observed mainly in EC: FD were IP of 31.5% of them (1391/4408) and 48.5% (1969/4058) of NIR. This despite the increasing trend in the number of FD staff. By type of funding, when the studies were supported by private sector there was a wider gap markedly unfavorable for women. CONCLUSIONS: Our results show that there is underrepresentation of women in research leadership, mainly those with private financing. This study reinforces the idea that there is still a long way to go in this field. More studies are necessary to identify the existing differences that allow the implementation of actions at the institutional and cultural level that promote gender equality in the field of clinical research.

Suitability of therapeutic effort in paediatric intensive care units: Opinion and attitude of professionals. / Adecuación del esfuerzo terapéutico en unidades de cuidados intensivos pediátricos: opinión y actitud de los profesionales.

OBJECTIVE: To determine the opinion and describe the attitude of different health professionals on suitability of therapeutic effort. METHOD: Multi-centre, cross-sectional observational study carried out with nurses and doctors who work in the paediatric intensive care units of four hospitals in the Madrid region. A self-administered questionnaire, previously piloted to assess its viability, was used and a sealed box was set up at the nursing station to hand it in. The analysis was performed using SPSS 21.0 software. RESULTS: The 98.9% of the respondents were in favour of suitability of therapeutic effort. Doctors consider that the decision is made with the agreement of the multidisciplinary staff and the child's parents (48.8%). Of the nurses, 51.1% believe that the decision is made by agreement with the doctors and parents. Of the nurses, 65.5% state that they are never asked about decision-making for their patients. Of the doctors, 75% are always or almost always asked. Fifty-seven percent of the nurses and 83% of the doctors feel capable of making decisions about suitability of therapeutic effort. Of the professionals, 77.2% believe that suitability is used less often than required. CONCLUSIONS: There are differences between doctors and nurses both in the perception of the decision-making model and in the way to proceed. Professionals seem not to follow any protocols or circuits in the decision-making process.

A novel Carcinoembryonic Antigen (CEA)-Targeted Trimeric Immunotoxin shows significantly enhanced Antitumor Activity in Human Colorectal Cancer Xenografts.

Immunotoxins are chimeric molecules, which combine antibody specificity to recognize and bind with high-affinity tumor-associated antigens (TAA) with the potency of the enzymatic activity of a toxin, in order to induce the death of target cells. Current immunotoxins present some limitations for cancer therapy, driving the need to develop new prototypes with optimized properties. Herein we describe the production, purification and characterization of two new immunotoxins based on the gene fusion of the anti-carcinoembryonic antigen (CEA) single-chain variable fragment (scFv) antibody MFE23 to α-sarcin, a potent fungal ribotoxin. One construct corresponds to a conventional monomeric single-chain immunotoxin design (IMTXCEAαS), while the other one takes advantage of the trimerbody technology and exhibits a novel trimeric format (IMTXTRICEAαS) with enhanced properties compared with their monomeric counterparts, including size, functional affinity and biodistribution, which endow them with an improved tumor targeting capacity. Our results show the highly specific cytotoxic activity of both immunotoxins in vitro, which was enhanced in the trimeric format compared to the monomeric version. Moreover, the trimeric immunotoxin also exhibited superior antitumor activity in vivo in mice bearing human colorectal cancer xenografts. Therefore, trimeric immunotoxins represent a further step in the development of next-generation therapeutic immunotoxins.

[Prevention and treatment of infectious diseases in diabetic patients]. / Prevención y tratamiento de la enfermedad infecciosa en personas con diabetes.

The bidirectional relationship between infectious diseases and diabetes is well-known. On the one hand, diabetes patients are at a higher risk of presenting with infectious diseases, possibly with more severity, and on the other hand, infectious diseases impair metabolic control in patients with diabetes. Population ageing arises partly due to an increased survival rate in chronic diseases, of which diabetes is amongst them. Improving infectious disease prevention could reduce complications arising from the former diseases, consequences of decompensated diabetes condition (morbidity, incapacity, hospital admissions, healthcare costs, and mortality rates) and result in improved quality of life in patients with diabetes. The current review presents the treatment of infectious diseases in patients with diabetes and the dealing with immuno-preventable diseases with the currently advised vaccinations.

Alcohol binge disrupts the rat intestinal barrier: the partial protective role of oleoylethanolamide.

BACKGROUND AND PURPOSE: Chronic alcohol consumption alters the gut-brain axis, but little is known about alcohol binge episodes on the functioning of the intestinal barrier. We investigated the influence of ethanol binges on bacterial translocation, gut inflammation and immunity, and tight junction (TJ) structure and the ability of the biolipid oleoylethanolamide (OEA) to prevent ethanol binge-induced intestinal barrier dysfunction. EXPERIMENTAL APPROACH: OEA was injected i.p. before repeated ethanol administration by oral gavage. Plasma, spleen, liver and mesenteric lymph nodes (MLN) were collected in sterile conditions for determination of bacterial load. Immune/inflammatory parameters, TJ proteins and apoptotic markers were determined in colonic tissue by RT-PCR and Western blotting. TJ ultrastructure was examined by transmission electron microscopy. KEY RESULTS: Ethanol binges induced bacterial translocation to the MLN (mainly) and spleen. Colonic tissues showed signs of inflammation, and activation of innate (Toll-like receptor-4) and adaptive (IgA) immune systems and TJ proteins (occludin and claudin-3) were decreased after ethanol binges. Pretreatment with OEA reduced intestinal inflammation and immune activation and partially preserved the TJ structure affected by alcohol binges but had no effect on alcohol-induced apoptosis. Ultrastructural analyses of colonic TJs revealed dilated TJs in all ethanol groups, with less electron-dense material in non-pretreated rats. The protective effects of i.p. OEA did not reduce bacterial translocation to the MLN. However, intragastric OEA administration significantly reduced plasma LPS levels and bacterial translocation to the MLN. CONCLUSION AND IMPLICATIONS: OEA-based pharmacotherapies could potentially be useful to treat disorders characterized by intestinal barrier dysfunction, including alcohol abuse.

Next generation sequencing in the diagnosis of Stargardt's disease. / La secuenciación masiva (NGS) como método diagnóstico en la enfermedad de Stargardt.

INTRODUCTION: Stargardt's disease is the most frequent form of inherited macular dystrophy in children and adults. It is a genetic eye disorder caused by mutations in ABCA4 gene with an autosomal recessive inheritance. ABCA4 is a very polymorphic and large gene containing 50 exons. The development of next generation sequencing (NGS) can be used for the genetic diagnosis of this disease. PATIENTS AND METHODS: A report is presented on two patients with a clinical diagnosis of Stargardt's disease whose genetic confirmation was performed by a NGS panel of 298 genes. RESULTS: Clinically, the patients showed bull's eye maculopathy and absence of flecks, and genetically they shared the Gly1961Glu mutation that could explain their common phenotype, together with c.C3056T:p.T1019M for case 1, and c.287del:p.Asn96Thrfs*19 for case 2. CONCLUSIONS: NGS is particularly useful in the diagnosis of Stargardt's disease as ABCA4 is a large gene with a high allelic heterogeneity that causes a wide range of clinical manifestations.

mTOR mutations in Smith-Kingsmore syndrome: Four additional patients and a review.

Smith-Kingsmore syndrome (SKS) OMIM #616638, also known as MINDS syndrome (ORPHA 457485), is a rare autosomal dominant disorder reported so far in 23 patients. SKS is characterized by intellectual disability, macrocephaly/hemi/megalencephaly, and seizures. It is also associated with a pattern of facial dysmorphology and other non-neurological features. Germline or mosaic mutations of the mTOR gene have been detected in all patients. The mTOR gene is a key regulator of cell growth, cell proliferation, protein synthesis and synaptic plasticity, and the mTOR pathway (PI3K-AKT-mTOR) is highly regulated and critical for cell survival and apoptosis. Mutations in different genes in this pathway result in known rare diseases implicated in hemi/megalencephaly with epilepsy, as the tuberous sclerosis complex caused by mutations in TSC1 and TSC2, or the PIK3CA-related overgrowth spectrum (PROS). We here present 4 new cases of SKS, review all clinical and molecular aspects of this disorder, as well as some characteristics of the patients with only brain mTOR somatic mutations.

Pharmacogenetic biomarkers of response in Crohn's disease.

Crohn's disease (CD) is a chronic condition, which affects the immune system. It can also affect any part of the digestive tract and be associated with external manifestations. The causes of the disease remain unknown, although it seems to be the result of a combination of factors, such as genetic predisposition, environment, lifestyle and the composition of the microbiota, among others. The treatment protocol begins with a change in eating and smoking habits, and is continued with different lines of treatment, including corticosteroids, immunomodulators and biologic therapy (infliximab and adalimumab), which have shown differences in response among patients, especially with biologic treatment. Several studies have considered the possibility that these differences in response are caused by the genetic variability of patients. Many genes have been investigated as potential predictors of response to biological drugs, such as ADAM17, ATG16L1, EMSY, CASP9, CCNY, CNTN5, FASLG, FCGR, NOD2, PTGER4, IL13, IL1B, IL27, IL11, IL17F, TNF and TNFR genes. In this review, we will gather the information on influence of gene polymorphisms investigated to date on response to biological drugs in CD patients.

Randomised crossover trial showed that using breast milk or sucrose provided the same analgesic effect in preterm infants of at least 28 weeks.

AIM: Repeated, ongoing exposure to pain influences the growth, cognitive and motor functions, behaviour, personality and neurodevelopment of preterm infants. We compared the analgesic effects of expressed breast milk (EBM) and 24% oral sucrose on preterm neonates during venipuncture. METHODS: This multicentre randomised, noninferiority, crossover trial focused on five neonatal university units in Madrid, Spain, from October 2013 to October 2014. It comprised 66 preterm infants born at less than 37 weeks and randomly split into two groups. They received either EBM or sucrose two minutes before venepuncture, together with nonnutritive sucking and swaddling, then the opposite procedure at a later point. Pain was measured with the premature infant pain profile (PIPP) and crying was also measured. RESULTS: There were no statistically significant differences between the groups. The PIPP scores were seven (4-9) with breast milk and six (4-8.25) with sucrose (p = 0.28). The 11 infants born at under 28 weeks of age showed higher median scores of nine (9-14) for breast milk and four (4-7) for sucrose (p = 0.009). CONCLUSION: EBM and 24% sucrose had the same analgesic effect during venipuncture in most of the preterm neonates, but sucrose worked better in extremely preterm infants.

Clinicobiological features and prognostic impact of diffuse large B-cell lymphoma component in the outcome of patients with previously untreated follicular lymphoma.

BACKGROUND: The co-existence at diagnosis of follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) components (FL/DLBCL) has been considered a transformed lymphoma and accordingly treated although clinicobiological information on these patients is scarce. The aim of this study was to analyze the initial features and outcome of FL/DLBCL patients in the rituximab era. PATIENTS AND METHODS: All patients consecutively diagnosed at a single institution with FL/DLBCL (n = 40), as well as those with pure FL (n = 328) or de novo DLBCL (n = 510) as controls. RESULTS: The proportion of the DLBCL component was highly variable (median 50%). In 29 FL/DLBCL cases analyzed, the cell of origin was GCB in 86%, ABC in 10% and unclassifiable in 4%. NOTCH1-2 was mutated in 10% of these cases. The proportion of DLBCL component did not impact on overall survival (OS). Regarding initial characteristics, patients with FL/DLBCL were closer to FL in terms of primary nodal origin, good performance status and advanced stage, whereas the other features were intermediate between FL and DLBCL. FL/DLBCL patients were treated as DLBCL with no further intensification. Complete response and primary refractory rates were 65% and 20%, respectively, with these figures being similar to DLBCL and worse than FL. Progression-free survival and OS were intermediate between FL and DLBCL (5-year OS: 85%, 73% and 63% for FL, FL/DLBCL and DLBCL, respectively). FL/DLBCL histology did not reach independent prognostic value for OS in the multivariate analyses. CONCLUSIONS: The outcome of FL/DLBCL patients is not worse than that of de novo DLBCL. These cases should be treated with immunochemotherapy as DLBCL, but intensification with ASCT may not be necessary. The biological insights of FL/DLBCL warrants further genetic and molecular studies.

Broadening the phenotypic spectrum of POP1-skeletal dysplasias: identification of POP1 mutations in a mild and severe skeletal dysplasia.

Processing of Precursor 1 (POP1) is a large protein common to the ribonuclease-mitochondrial RNA processing (RNase-MRP) and RNase-P (RMRP) endoribonucleoprotein complexes. Although its precise function is unknown, it appears to participate in the assembly or stability of both complexes. Numerous RMRP mutations have been reported in individuals with cartilage-hair hypoplasia (CHH) but, to date, only three POP1 mutations have been described in two families with features similar to anauxetic dysplasia (AD). We present two further individuals, one with severe short stature and a relatively mild skeletal dysplasia and another in whom AD was suspected. Biallelic POP1 mutations were identified in both. A missense mutation and a novel single base deletion were detected in proband 1, p.[Pro582Ser]:[Glu870fs*5]. Markedly reduced abundance of RMRP and elevated levels of pre5.8s rRNA was observed. In proband 2, a homozygous novel POP1 mutation was identified, p.[(Asp511Tyr)];[(Asp511Tyr)]. These two individuals show the phenotypic extremes in the clinical presentation of POP1-dysplasias. Although CHH and other skeletal dysplasias caused by mutations in RMRP or POP1 are commonly cited as ribosomal biogenesis disorders, recent studies question this assumption. We discuss the past and present knowledge about the function of the RMRP complex in skeletal development.

[Questionnaire to evaluate the importance of the family in nursing care. Validation of the Spanish version (FINC-NA)]. / Cuestionario para evaluar la importancia de la familia en los cuidados de enfermería. Validación de la versión española (FINC-NA).

BACKGROUND: The nursing profession is focused on patient care, without forgetting that patients are part of a social group, the family. The aim of this study was the adaptation of the "Families' Importance in Nursing Care-Nurses' Attitudes" (FINC-NA) scale to the Spanish language and its validation. METHODS: A descriptive cross-sectional study was carried out, using the bidirectional translation method for linguistic-cultural adaptation. It was applied to the nursing staff in the Paediatric Department of a University Hospital in Madrid. To evaluate the psychometric properties of the Spanish version, reliability, internal consistence and construct validity were calculated. RESULTS: The sample consisted of 274 professionals. Cronbach´s Alpha coefficient for the total scale was 0.864, oscillating between 0.888 and 0.769 in the subscales. The principal components factor analysis identified 4 factors, which explained 54.22% of total variance. CONCLUSIONS: The new instrument makes it possible to determine the importance nurses give to participation by family members and their attitude to involving the latter in patient care, and the possibility of involving them in planning. It has been adapted to the Spanish population with good psychometrics results and enough evidence for its use in this context.

Ascorbic acid PEG-2L is superior for early morning colonoscopies in colorectal cancer screening programs: a prospective non-randomized controlled trial.

BACKGROUND: The quality of colon cleansing and the tolerability of anterograde preparation are essential to the success of colorectal cancer screening. AIM: To compare the tolerability and efficacy of low-volume preparations vs the standard regimen in individuals scheduled for an early morning colonoscopy. STUDY: Participants in a population-based colorectal cancer screening program using the fecal immunochemical test who were scheduled for a colonoscopy from 09:00 a.m. to 10:20 a.m. were prospectively included and assigned to: (1) control group (PEG-ELS 4L): PEG 4L and electrolytes; (2) group AscPEG-2L: a combination of PEG and ascorbic acid 2L; and (3) group PiMg: sodium picosulfate and magnesium citrate 500 mL plus 2L of clear fluids. Tolerability was evaluated with a questionnaire and the quality of bowel preparation with the Boston Bowel Preparation Scale. RESULTS: A total of 292 participants were included: 98 in the PEG-ELS 4L control group, 96 in the AscPEG-2L study group and 98 in the PiMg study group. Low-volume treatments were better tolerated than the standard solution (AscPEG-2L 94.8% and PiMg 93.9% vs PEG-ELS 4L 75.5%; p < 0.0001). The effectiveness of AscPEG-2L was superior to that of PEG-ELS 4L and PiMg (p = 0.011 and p = 0.032, respectively). Patient acceptance was higher for single-dose than for split-dose administration but efficacy was higher with the split dose than with other doses. CONCLUSIONS: In early morning colonoscopies, ascPEG-2L appears to be the best option, especially when administered in a split-dose.