Switching from onabotulinum toxin A to abobotulinum toxin A for treating detrusor overactivity in spinal cord injured patient, does it really work?

AIM: To assess the efficacy of switching to Abobotulinumtoxin A (ATA) intradetrusor injections (IDI) after failure of Onabotulinumtoxin A (OTA) IDI for the treatment of neurogenic detrusor overactivity in patients with spinal cord injury (SCI). MATERIALS AND METHODS: A single-centre retrospective chart review study. All SCI patients who started OTA IDI after 2011 and had an ATA IDI switch were included. The primary outcome was the clinical and urodynamic efficacy of the switch to ATA IIDs at the last follow-up. Secondary outcomes were initial efficacy, duration of ATA treatment, and patient outcome including the occurrence of augmentation enterocystoplasty at last follow-up. RESULTS: Sixty-two patients were included. Eighteen patients (28.9%) were initially responders to ATA IDI. Nine patients (14.5%) remained responders at last follow-up after a median of 17 months (AE 8.8-29). Thirty-two patients (51.6%) had had or were awaiting augmentation enterocystoplasty with a follow-up time of 18.5 months (IQR 8-27). Eleven patients (17.7%) were on ATA IDI with low efficacy. Seven patients (11.3%) were switched back to OTA and 3 patients (4.8%) changed their voiding pattern. CONCLUSION: Switching from OTA to ATA toxin for IDI in the treatment of detrusor overactivity after spinal cord injury have long-term efficacy for a limited number of patients but may delay the need for surgery.

All-cause mortality and cardiovascular events in a Spanish nonagenarian cohort according to type 2 diabetes mellitus status and established cardiovascular disease.

BACKGROUND: Despite the progressive aging of the population in industrialized countries, few studies have focused on the natural history of cardiovascular disease in the very old, and recommendations on prevention of cardiovascular disease in this population are lacking. We aimed to analyze all-cause mortality and cardiovascular events according to prevalent type 2 diabetes mellitus and established cardiovascular disease in nonagenarians from a Mediterranean population. METHODS: We analyzed the primary health records of all nonagenarians living in the Community of Madrid (N = 59,423) and collected data for 4 groups: Group 1, individuals without T2DM or established CVD (T2DM-, CVD-); Group 2, individuals without T2DM but with established CVD (T2DM-, CVD +); Group 3, individuals with T2DM but without established CVD (T2DM + , CVD-); and Group 4, individuals with both T2DM and established CVD (T2DM + , CVD +), taking into account the influence of sex on the outcomes. Follow-up was 2.5 years. The primary outcomes were cumulative incidence and incidence density rates for all-cause mortality, non-fatal myocardial infarction, non-fatal stroke (the first composite primary outcome [CPO1]), combined with heart failure (CPO2). We evaluated the adjusted effect of each group on all-cause mortality (Cox regression). RESULTS: Mean age was 93.3 ± 2.8 years (74.2% women). Hypertension, dyslipidemia, heart failure, albuminuria, and estimated glomerular filtration rate < 60 mL/min/1.73 m2 were significantly more prevalent in G4 than in the other groups (all p values < 0.001). We observed significantly higher cumulative incidence rates for all-cause mortality, CPO1, and CPO2 in participants belonging to G4 (all p values ≤ 0.001). People in G2 presented higher rates of all-cause mortality, heart failure, CPO1, and CPO2 than people in G3 (all p values ≤ 0.001). In the fully adjusted model, G4 independently predicted all-cause mortality (HR = 1.48 [95% CI, 1.40 to 1.57] vs reference G1 [p < 0.01]). In addition, significant HRs were recorded for cardiovascular disease alone (G2) and type 2 diabetes mellitus alone (G3) (1.13 and 1.14, respectively; both p values < 0.01). CONCLUSIONS: In Spanish nonagenarians, established cardiovascular disease and type 2 diabetes mellitus conferred a modest risk of all-cause mortality. However, the simultaneous presence of both conditions conferred the highest risk of all-cause mortality.

[Factors associated with mortality due to SARS-CoV-2 in the population over 75 years of age in the Community of Madrid]. / Factores asociados con la mortalidad por SARS-CoV-2 en la población mayor de 75 años de la Comunidad de Madrid.

Objective: Various studies have identified factors associated with risk of mortality in patients with SARS-CoV-2 infection. However, their sample size has often been limited and their results partially contradictory. This study evaluated factors associated with COVID-19 mortality in the population of Madrid over 75 years of age, in infected patients, and in hospitalized patients up to January 2021. Patients and methods: This population-based cohort study analyzed all residents of the Community of Madrid born before January 1, 1945 who were alive as of December 31, 2019. Demographic and clinical data were obtained from primary care electronic medical records (PC-Madrid), data on hospital admissions from the Conjunto Mínimo Básico de Datos (CMBD, Minimum Data Set), and data on mortality from the Índice Nacional de Defunciones (INDEF, National Death Index). Data on SARS-CoV-2 infection, hospitalization, and death were collected from March 1, 2020 to January 31, 2021. Results: A total of 587,603 subjects were included in the cohort. Of them, 41,603 (7.1%) had confirmed SARS-CoV-2 infection, of which 22,362 (53.7% of the infected individuals) were hospitalized and 11,251 (27%) died. Male sex and age were the factors most closely associated with mortality, though many comorbidities also had an influence. The associations were stronger in the analysis of the total population than in the analysis of infected or hospitalized patients. Mortality among hospitalized patients was lower during the second wave (33.4%) than during the first wave (41.2%) of the pandemic. Conclusion: Age, sex, and numerous comorbidities are associated with risk of death due to COVID-19. Mortality in hospitalized patients declined notably after the first wave of the pandemic.

Spinal cord injury: A multisystem physiological impairment/dysfunction.

Spinal cord injury (SCI) is a complex disease that affects not only sensory and motor pathways below the neurological level of injury (NLI) but also all the organs and systems situated below this NLI. This multisystem impairment implies comprehensive management in dedicated SCI specialized centers, by interdisciplinary and multidisciplinary teams, able to treat not only the neurological impairment, but also all the systems and organs affected. After a brief history of the Spinal Cord Medicine, the author describes how to determine the level and severity of a SCI based on the International Standards for Neurological Classification of Spinal Cord Injury and the prognosis factors of recovery. This article provides also a review of the numerous SCI-related impairments (except for urinary, sexual problems and pain treated separately in this issue), their principles of management and related complications.

Effectiveness of standardized nursing care plans to achieve A1C, blood pressure, and LDL-C goals among people with poorly controlled type 2 diabetes mellitus at baseline: four-year follow-up study.

BACKGROUND: No studies that have measured the role of nursing care plans in patients with poorly controlled type 2 diabetes mellitus. Our objectives were firstly, to evaluate the effectiveness of implementing Standardized languages in Nursing Care Plans (SNCP) for improving A1C, blood pressure and low density lipoprotein cholesterol (ABC goals) in patients with poorly controlled type 2 diabetes mellitus at baseline (A1C ≥7%, blood pressure ≥ 130/80 mmHg, and low-density lipoprotein cholesterol≥100 mg/dl) compared with Usual Nursing Care (UNC). Secondly, to evaluate the factors associated with these goals. METHODS: A four-year prospective follow-up study among outpatients with type 2 diabetes mellitus: We analyzed outpatients of 31 primary health centers (Madrid, Spain), with at least two A1C values (at baseline and at the end of the study) who did not meet their ABC goals at baseline. A total of 1916 had A1C ≥7% (881 UNC versus 1035 SNCP). Two thousand four hundred seventy-one had systolic blood pressure ≥ 130 mmHg (1204 UNC versus 1267 SNCP). One thousand one hundred seventy had diastolic blood pressure ≥ 80 mmHg (618 UNC versus 552 SNCP); and 2473 had low-density lipoprotein cholesterol ≥100 mg/dl (1257 UNC versus 1216 SNCP). Data were collected from computerized clinical records; SNCP were identified using NANDA and NIC taxonomies. RESULTS: More patients cared for using SNCP achieved in blood pressure goals compared with patients who received UNC (systolic blood pressure: 29.4% versus 28.7%, p = 0.699; diastolic blood pressure: 58.3% versus 53.2%, p = 0.08), but the differences did not reach statistical significance. For A1C and low-density lipoprotein cholesterol goals, there were no significant differences between the groups. Coronary artery disease was a significant predictor of blood pressure and low-density lipoprotein cholesterol goals. CONCLUSIONS: In patients with poorly controlled type 2 diabetes mellitus, there is not enough evidence to support the use of SNCP instead of with UNC with the aim of helping patients to achieve their ABC goals. However, the use of SNCP is associated with a clear trend of a achievement of diastolic blood pressure goals.

Incidence, surgical procedures, and outcomes of hip fracture among elderly type 2 diabetic and non-diabetic patients in Spain (2004-2013).

UNLABELLED: Hip fracture is a serious public health problem. We used Spanish hospital discharge data to examine trends in 2004-2013 in the incidence of hip fracture among elderly patients. We found that hip fracture incidence is higher in subjects with than without diabetes and is much higher among women than men. INTRODUCTION: This study aimed to describe trends in the incidence of hip fracture hospitalizations, use of surgical procedures, and hospital outcomes among elderly patients with and without type 2 diabetes mellitus (T2DM) in Spain, 2004-2013. METHODS: We selected all patients with a discharge primary diagnosis of hip fracture using the Spanish national hospital discharge database. Discharges were grouped by diabetes status: Incidences were calculated overall and stratified by diabetes status and year. We analyzed surgical procedures, length of hospital stay (LOHS), and in-hospital mortality (IHM). Multivariate analysis was adjusted by age, year, comorbidity, and in-hospital complications (IHC). RESULTS: From 2004 to 2013, 432,760 discharges with hip fracture were identified (21.3 % suffered T2DM). Incidence among diabetic men and women increased until year 2010 and then remained stable. Diabetic women have three times higher incidence than diabetic men. Incidences and IHC were higher among patients with diabetes beside sex. The proportion of patients that underwent internal fixation increased for all groups of patients and the arthroplasty repair decreased. After multivariate analysis, IHM has improved over the study period for all patients. Suffering diabetes was associated to higher IHM in women (odds ratio (OR) 1.12; 95 % confidence interval (CI) 1.07-1.17). CONCLUSIONS: Hip fracture incidence is higher in subjects with than without diabetes and is much higher among women than men. In diabetic patients, incidence rates increased initially but have leveled from 2010 onwards. For all groups, the use of internal fixation has increased overtime and IHM and LOHS have decreased from 2004 to 2013.

Sepsis of the hip due to pressure sore in spinal cord injured patients: advocacy for a one-stage surgical procedure.

STUDY DESIGN: Retrospective study reporting characteristics and management of septic arthritis of the hip due to pressure sores in spinal cord-injured patients. OBJECTIVES: To describe clinical and biological data of septic arthritis of the hip and its treating management. SETTING: The database of the regional SCI referral center, Nantes, France. METHODS: We retrospectively collected data from 33 cases of septic arthritis of the hip in the medical files of 26 patients. RESULTS: We analyzed 33 cases of septic arthritis of the hip treated in one French referent center for spinal cord-injured patients from January 1988 to December 2009. Most patients had a thoracic complete paraplegia and nearly two-third (17 out of 26) had no systematic follow-up. In 25 out of 33 cases, the septic arthritis of the hip was due to a trochanteric pressure sore. The causal pressure sore was most frequently associated with a persistent drainage. The standard radiological examination led to the diagnosis in 30 cases and, in 7 questionable cases, magnetic resonance imaging was more contributory. Surgery always consisted of a wide carcinological-like excision and of a subtrochanteric proximal femoral resection including both greater and lesser trochanters. A musculocutaneous flap was realized for all cases and the choice of the muscle depended on the localization of the causal pressure sore but also of the remaining choices, as most of the patients had already undergone a prior surgery. An antibiotic treatment was adapted to multiple samples during surgery. CONCLUSION: We do advocate for a one-stage procedure including a subtrochanteric proximal femoral resection and a musculocutaneous flap.

Cytokine release assays: current practices and future directions.

As a result of the CD28 superagonist biotherapeutic monoclonal antibody (TGN 1412) "cytokine storm" incident, cytokine release assays (CRA) have become hazard identification and prospective risk assessment tools for screening novel biotherapeutics directed against targets having a potential risk for eliciting adverse pro-inflammatory clinical infusion reactions. Different laboratories may have different strategies, assay formats, and approaches to the reporting, interpretation, and use of data for either decision making or risk assessment. Additionally, many independent contract research organizations (CROs), academic and government laboratories are involved in some aspect of CRA work. As a result, while some pharmaceutical companies are providing CRA data as part of the regulatory submissions when necessary, technical and regulatory practices are still evolving to provide data predictive of cytokine release in humans and that are relevant to safety. This manuscript provides an overview of different approaches employed by the pharmaceutical industry and CROs, for the use and application of CRA based upon a survey and post survey follow up conducted by ILSI-Health and Environmental Sciences Institute (HESI) Immunotoxicology Committee CRA Working Group. Also discussed is ongoing research in the academic sector, the regulatory environment, current limitations of the assays, and future directions and recommendations for cytokine release assays.

A Development and Implementation of a Preconception Counseling Program for Black Women and Men in the Southeastern United States: A Pilot Protocol.

Introduction: Racial/ethnic disparities in maternal mortality rates represent one of the most significant areas of disparities amongst all conventional population perinatal health measures in the U.S. The alarming trends and persistent disparities of outcomes by race/ethnicity and geographic location reinforce the need to focus on ensuring quality and safety of maternity care for all women. Despite complex multilevel factors impacting maternal mortality and morbidity, there are evidence-based interventions that, when facilitated consistently and properly, are known to improve the health of mothers before, during and after pregnancy. The objective of this project is to test implementation of pre-conception counseling with father involvement in community-based settings to improve cardiovascular health outcomes before and during pregnancy in southeastern United States. Methods and Analysis: This study has two components: a comprehensive needs and assets assessment and a small-scale pilot study. We will conduct a community informed needs and assets assessment with our diverse stakeholders to identify opportunities and barriers to preconception counseling as well as develop a stakeholder-informed implementation plan. Next, we will use the implementation plan to pilot preconception counseling with father involvement in community-based settings. Finally, we will critically assess the context, identify potential barriers and facilitators, and iteratively adapt the way preconception counseling can be implemented in diverse settings. Results of this research will support future research focused on identifying barriers and opportunities for scalable and sustainable public health approaches to implementing evidence-based strategies that reduce maternal morbidity and mortality in the southeastern United States' vulnerable communities. Discussion: Findings will demonstrate that preconception counseling can be implemented in community health settings in the southeastern United States. Furthermore, this study will build the capacity of community-based organizations in addressing the preconception health of their clients. We plan for this pilot to inform a larger scaled-up clinical trial across community health settings in multiple southeastern states.

Incidence of T2DM and the role of baseline glycaemic status as a determinant in a metropolitan population in northern Madrid (Spain).

AIM: To estimate the incidence of T2DM and assess the effect of pre-T2DM (isolated impaired fasting glucose [iIFG], isolated impaired glucose tolerance [iIGT] or both) on progress to T2DM in the adult population of Madrid. METHODS: Population-based cohort comprising 1,219 participants (560 normoglycaemic and 659 preT2DM [418 iIFG, 70 iIGT or 171 IFG-IGT]). T2DM was defined based on fasting plasma glucose or HbA1c or use of glucose-lowering medication. We used a Cox model with normoglycaemia as reference category. RESULTS: During 7.26 years of follow-up, the unadjusted incidence of T2DM was 11.21 per 1000 person-years (95 %CI, 9.09-13.68) for the whole population, 5.60 (3.55-8.41) for normoglycaemic participants and 16.28 (12.78-20.43) for pre-T2DM participants. After controlling for potential confounding factors, the baseline glycaemic status was associated with higher primary effect on developing T2DM was iIGT (HR = 3.96 [95 %CI, 1.93-8.10]) and IFG-IGT (3.42 [1.92-6.08]). The HR for iIFG was 1.67 (0.96-2.90). Obesity, as secondary effect, was strongly significantly associated (HR = 2.50 [1.30-4.86]). CONCLUSIONS: Our incidence of T2DM is consistent with that reported elsewhere in Spain. While baseline iIGT and IFG-IGT behaved a primary effect for progression to T2DM, iIFG showed a trend in this direction.

[A report of the SFGM-TC on the interactions between national transplant coordination and local coordinators in allogeneic stem cell transplantation activity]. / Interactions entre coordination nationale de greffe et coordinateurs locaux.

In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) set up the third annual series of workshops which brought together practitioners from all member centers and took place in October 2012 in Lille. The main aim of this session was to describe the relations between the national transplant coordination office of the French registry and local stem cell transplantation coordinators throughout France.

Real-world data in primary care: validation of diagnosis of atrial fibrillation in primary care electronic medical records and estimated prevalence among consulting patients'.

BACKGROUND: Primary care electronic medical records contain clinical-administrative information on a high percentage of the population. Before this information can be used for epidemiological purposes, its quality must be verified. This study aims to validate diagnoses of atrial fibrillation (AF) recorded in primary care electronic medical records and to estimate the prevalence of AF in the population attending primary care consultations. METHODS: We performed a cross-sectional validation study of all diagnoses of AF recorded in primary care electronic medical records in Madrid (Spain). We also performed simple random sampling of diagnoses of AF (ICPC-2 code K78) registered by 55 physicians and random age- and sex-matched sampling of the records that included a diagnosis of AF. Electrocardiograms, echocardiograms, and hospital discharge or cardiology clinic reports were matched. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and overall agreement were calculated using the kappa statistic (κ). The prevalence of AF in the community of Madrid was estimated considering the sensitivity and specificity obtained in the validation. All calculations were performed overall and by sex and age groups. RESULTS: The degree of agreement was very high (κ = 0.952), with a sensitivity of 97.84%, specificity of 97.39%, PPV of 97.37%, and NPV of 97.85%. The prevalence of AF in the population aged over 18 years was 2.41% (95%CI 2.39-2.42% [2.25% in women and 2.58% in men]). This increased progressively with age, reaching 16.95% in those over 80 years of age (15.5% in women and 19.44% in men). CONCLUSIONS: The validation results obtained enable diagnosis of AF recorded in primary care to be used as a tool for epidemiological studies. A high prevalence of AF was found, especially in older patients.

Factors associated with mortality due to SARS-CoV-2 in the population over 75 years of age in the Community of Madrid.

OBJECTIVE: Various studies have identified factors associated with risk of mortality in patients with SARS-CoV-2 infection. However, their sample size has often been limited and their results partially contradictory. This study evaluated factors associated with COVID-19 mortality in the population of Madrid over 75 years of age, in infected patients, and in hospitalized patients up to January 2021. PATIENTS AND METHODS: This population-based cohort study analyzed all residents of the Community of Madrid born before January 1, 1945 who were alive as of December 31, 2019. Demographic and clinical data were obtained from primary care electronic medical records (PC-Madrid), data on hospital admissions from the Conjunto Mínimo Básico de Datos (CMBD, Minimum Data Set), and data on mortality from the Índice Nacional de Defunciones (INDEF, National Death Index). Data on SARS-CoV-2 infection, hospitalization, and death were collected from March 1, 2020 to January 31, 2021. RESULTS: A total of 587,603 subjects were included in the cohort. Of them, 41,603 (7.1%) had confirmed SARS-CoV-2 infection, of which 22,362 (53.7% of the infected individuals) were hospitalized and 11,251 (27%) died. Male sex and age were the factors most closely associated with mortality, though many comorbidities also had an influence. The associations were stronger in the analysis of the total population than in the analysis of infected or hospitalized patients. Mortality among hospitalized patients was lower during the second wave (33.4%) than during the first wave (41.2%) of the pandemic. CONCLUSION: Age, sex, and numerous comorbidities are associated with risk of death due to COVID-19. Mortality in hospitalized patients declined notably after the first wave of the pandemic.

Effect of depression on mortality in type 2 diabetes mellitus after 8 years of follow-up. The DIADEMA study.

AIM: To assess the effect of depression on all-cause mortality in patients with type 2 diabetes mellitus (T2DM) followed up during 8 years in primary care in Spain. METHODS: Depression was diagnosed according to MINI 5.0.0 questionnaire, physician-diagnosis or following antidepressant therapy for at least two months in 3923 people with T2DM. We analyzed mortality-rates/10,000 person-years. We compared survival according to baseline depression with Kaplan-Meier estimates and the log-rank test. We performed Cox proportional hazard model analyses. RESULTS: Baseline depression was diagnosed in 22.1% of participants. Mortality was higher in patients with depression (31.9% vs. 26.9%; p = 0.003), who had a significantly poorer survival (median survival = 7.4 vs. 7.8 years, respectively; Log Rank = 15.83; p < 0.001). Depression showed an adjusted mortality hazard ratio (HR) = 1.40 (95%CI:1.20-1.65; p < 0.001). The strongest predictive factors were: age >75 years (HR = 6.04; 95%CI:4.62-7.91; p < 0.001), insulin use (HR = 2.37; 95%CI:1.86-3.00; p < 0.001), lower limb amputation (HR = 1.99; 95%CI:1.28-3.11; p = 0.002), heart failure (HR = 1.94; 95%CI:1.63-2.30; p < 0.001), and male gender (HR = 1.90; 95%CI:1.59-2.27). CONCLUSION: In a Spanish cohort of older T2DM patients, depression was associated with a higher mortality risk. More efforts are needed to minimize the influence of depression on mortality in people with T2DM and to implement measures that allow its early diagnosis and effective treatment.

Cardiovascular risk factors associated with acute myocardial infarction and stroke in the MADIABETES cohort.

We aimed to develop two models to estimate first AMI and stroke/TIA, respectively, in type 2 diabetes mellitus patients, by applying backward elimination to the following variables: age, sex, duration of diabetes, smoking, BMI, and use of antihyperglycemic drugs, statins, and aspirin. As time-varying covariates, we analyzed blood pressure, albuminuria, lipid profile, HbA1c, retinopathy, neuropathy, and atrial fibrillation (only in stroke/TIA model). Both models were stratified by antihypertensive drugs. We evaluated 2980 patients (52.8% women; 67.3 ± 11.2 years) with 24,159 person-years of follow-up. We recorded 114 cases of AMI and 185 cases of stroke/TIA. The factors that were independently associated with first AMI were age (≥ 75 years vs. < 75 years) (p = 0.019), higher HbA1c (> 64 mmol/mol vs. < 53 mmol/mol) (p = 0.003), HDL-cholesterol (0.90-1.81 mmol/L vs. < 0.90 mmol/L) (p = 0.002), and diastolic blood pressure (65-85 mmHg vs. < 65 mmHg) (p < 0.001). The factors that were independently associated with first stroke/TIA were age (≥ 75 years vs. < 60 years) (p < 0.001), atrial fibrillation (first year after the diagnosis vs. more than one year) (p = 0.001), glomerular filtration rate (per each 15 mL/min/1.73 m2 decrease) (p < 0.001), total cholesterol (3.88-6.46 mmol/L vs. < 3.88 mmol/L) (p < 0.001), triglycerides (per each increment of 1.13 mmol/L) (p = 0.031), albuminuria (p < 0.001), neuropathy (p = 0.01), and retinopathy (p = 0.023).

Folate hydrolase-1 (FOLH1) is a novel target for antibody-based brachytherapy in Merkel cell carcinoma.

BACKGROUNDS: Folate Hydrolase-1 (FOLH1; PSMA) is a type II transmembrane protein, luminally expressed by solid tumour neo-vasculature. Monoclonal antibody (mAb), J591, is a vehicle for mAb-based brachytherapy in FOLH1+ cancers. Brachytherapy is a form of radiotherapy that involves placing a radioactive material a short distance from the target tissue (e.g., on the skin or internally); brachytherapy is commonly accomplished with the use of catheters, needles, metal seeds and antibody or small peptide conjugates. Herein, FOLH1 expression in primary (p) and metastatic (m) Merkel cell carcinoma (MCC) is characterized to determine its targeting potential for J591-brachytherapy. MATERIALS & METHODS: Paraffin sections from pMCC and mMCC were evaluated by immunohistochemistry for FOLH1. Monte Carlo simulation was performed using the physical properties of conjugated radioisotope lutetium-177. Kaplan-Meier survival curves were calculated based on patient outcome data and FOLH1 expression. RESULTS: Eighty-one MCC tumours were evaluated. 67% (54/81) of all cases, 77% (24/31) pMCC and 60% (30/50) mMCC tumours were FOLH1+. Monte Carlo simulation showed highly localized ionizing tracks of electrons emitted from the targeted neo-vessel. 42% (34/81) of patients with FOLH1+/- MCC had available survival data f or analysis. No significant differences in our limited data set were detected based on FOLH1 status (p = 0.4718; p = 0.6470), staining intensity score (p = 0.6966; p = 0.9841) or by grouping staining intensity scores (- and + vs. ++, +++, +++) (p = 0.8022; p = 0.8496) for MCC-specific survival or recurrence free survival, respectively. CONCLUSIONS: We report the first evidence of prevalent FOLH1 expression within MCC-associated neo-vessels, in 60-77% of patients in a large MCC cohort. Given this data, and the need for alternatives to immune therapies it is appropriate to explore the safety and efficacy o f FOLH1-targeted brachytherapy for MCC.

T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice.

Mice rendered deficient in the production of interleukin 10 (IL-10-/-) develop a chronic inflammatory bowel disease (IBD) that predominates in the colon and shares histopathological features with human IBD. Our aim was to identify which cell type(s) can mediate colitis in IL-10-/- mice. We detected an influx of immunoglobulin-positive cells into the colon and the presence of colon-reactive antibodies in the serum of IL-10-/- mice. To assess a pathogenic role for B cells, we generated a B cell-deficient (B-/-) strain of IL-10-/- mice. B-/-IL-10-/- mice acquired a severe colitis analogous to that IL-10-/- mice, implying that B cells were not the primary mediator of IBD in this model. A series of cell transfer experiments was performed to assess a pathogenic role for T cells. When IL-10-/- T cell-enriched lamina propria lymphocytes (LPL) or intraepithelial lymphocytes (IEL) were transferred into immunodeficient recombinase-activating gene (RAG)-2-/- recipients, a mild to severe colitis developed, depending on the cell number transferred. Lymphocytes recovered from the colon of transplanted RAG-2-/- mice with colitis were predominantly alpha beta TCR+CD4+, including a large proportion of CD4+CD8 alpha + cells. These cells were also CD45RB-/low and CD44+, indicative of an activated/memory population. Individual populations of CD4+CD8 alpha-, CD4+CD8 alpha + and CD4-CD8 alpha + T cells were then isolated from the lamina propria compartment of IL-10-/- mice and transferred into RAG-2-/- recipients. Only IL-10-/- CD4-expressing LPL, including both the CD4+CD8 alpha- and CD4+CD8 alpha + populations, induced colitis in recipient mice. Interferon-gamma, but little to no IL-4, was produced by CD4+CD8 alpha- and CD4+CD8 alpha + LPL recovered from the inflamed colons of RAG-2-/- recipients implicating alpha T helper cell 1 (TH1)-mediated response. We thus conclude that colitis in IL-10-/- mice is predominantly mediated by TH1-type alpha beta TCR+ T cells expressing CD4 alone, or in combination with the CD8 alpha molecule.

[Baseline risk of Diabetes Mellitus in Primary Health Care Services by FINDRISC test, associated factors and clinical outcome after 18 months of follow-up]. / Riesgo basal de Diabetes Mellitus en Atención Primaria según cuestionario FINDRISC, factores asociados y evolución clínica tras 18 meses de seguimiento.

OBJECTIVE: To estimate the risk of Diabetes Mellitus in Primary Health Care Services and diabetes incidence after 18 months of follow-up. MATERIAL AND METHODS: A multicenter study, with a first cross-sectional phase, to estimate the risk of Diabetes using the FINRISC test in 261 patients without Diabetes Mellitus treated in Primary Health Care Services. A second phase was carried out to assess Diabetes incidence after 18 months of follow-up. RESULTS: 19.5% had an elevated risk of Diabetes Mellitus (FINDRISC score ≥15). The independent variables after adjusting for gender, which are not included in the FINDRISC test and were associated with increased risk of Diabetes, were low educational level and chronic ischemia of lower limbs. After 18 months of follow-up, 7.8% of patients with FINDRISC score ≥15 developed Diabetes versus 1.9% of patients with FINDRISC score <15. CONCLUSIONS: One out of five patients without Diabetes who are treated in Primary Care Health Services have a FINDRISC score ≥15, this being associated with low educational level and peripheral vascular disease, regardless of gender. The FINDRISC score ≥15 has a short-term association with a high risk of developing Diabetes Mellitus.