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.

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.

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).

A case report of orbital Langerhans cell histiocytosis presenting as a orbital cellulitis. / Caso clínico de histiocitosis de células de Langerhans presentándose como una celulitis orbitaria.

CLINICAL CASE: A 10-year-old girl was seen with a 3-week history of right upper lid swelling and with no other symptoms or fever. There was no recent history of sinusitis, trauma, or previous infection involving the periorbital area, or response to oral antibiotic treatment. Orbital computed tomography showed a lesion involving the upper margin of the orbit, and bone destruction at the orbital roof. Biopsy performed revealed the presence of Langerhans cell Histiocytosis. The lesion was surgically debulked and corticosteroids were used intra-operatively. The lesion responded to treatment. DISCUSSION: The orbital involvement of Langerhans cell histiocytosis, despite its low incidence, should be considered in the examination of acute peri-orbital swelling. It usually presents as an osteolytic lesion, and it is confirmed with a histological examination and immunohistochemical techniques for CD1a and S100. An interdisciplinary approach is recommended to rule out multifocal or multisystemic diseases, as well as to develop an appropriate treatment strategy.

Performance of the Finnish Diabetes Risk Score and a Simplified Finnish Diabetes Risk Score in a Community-Based, Cross-Sectional Programme for Screening of Undiagnosed Type 2 Diabetes Mellitus and Dysglycaemia in Madrid, Spain: The SPREDIA-2 Study.

AIM: To evaluate the performance of the Finnish Diabetes Risk Score (FINDRISC) and a simplified FINDRISC score (MADRISC) in screening for undiagnosed type 2 diabetes mellitus (UT2DM) and dysglycaemia. METHODS: A population-based, cross-sectional, descriptive study was carried out with participants with UT2DM, ranged between 45-74 years and lived in two districts in the north of metropolitan Madrid (Spain). The FINDRISC and MADRISC scores were evaluated using the area under the receiver operating characteristic curve method (ROC-AUC). Four different gold standards were used for UT2DM and any dysglycaemia, as follows: fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), HbA1c, and OGTT or HbA1c. Dysglycaemia and UT2DM were defined according to American Diabetes Association criteria. RESULTS: The study population comprised 1,426 participants (832 females and 594 males) with a mean age of 62 years (SD = 6.1). When HbA1c or OGTT criteria were used, the prevalence of UT2DM was 7.4% (10.4% in men and 5.2% in women; p<0.01) and the FINDRISC ROC-AUC for UT2DM was 0.72 (95% CI, 0.69-0.74). The optimal cut-off point was ≥13 (sensitivity = 63.8%, specificity = 65.1%). The ROC-AUC of MADRISC was 0.76 (95% CI, 0.72-0.81) with ≥13 as the optimal cut-off point (sensitivity = 84.8%, specificity = 54.6%). FINDRISC score ≥12 for detecting any dysglycaemia offered the best cut-off point when HbA1c alone or OGTT and HbA1c were the criteria used. CONCLUSIONS: FINDRISC proved to be a useful instrument in screening for dysglycaemia and UT2DM. In the screening of UT2DM, the simplified MADRISC performed as well as FINDRISC.

Risk factors and outcome of graft failure after HLA matched and mismatched unrelated donor hematopoietic stem cell transplantation: a study on behalf of SFGM-TC and SFHI.

Graft failure remains a severe complication of hematopoietic stem cell transplantation (HSCT). Several risk factors have already been published. In this study, we re-evaluated them in a large cohort who had the benefit of the recent experience in HSCT (2006-2012). Data from 4684 unrelated donor HSCT from 2006 to 2012 were retrospectively collected from centers belonging to the French Society for Stem Cell Transplantation. Among the 2716 patients for whom HLA typing was available, 103 did not engraft leading to a low rate of no engraftment at 3.8%. In univariate analysis, only type of disease and status of disease at transplant for malignant diseases remained significant risk factors (P=0.04 and P<0.0001, respectively). In multivariate analysis, only status of disease was a significant risk factor (P<0.0001). Among the 61 patients who did not engraft and who were mismatched for 1 HLA class I and/or HLA-DP, 5 donor-specific antibodies (DSAs) were detected but only 1 was clearly involved in graft failure, for the others their role was more questionable. Second HSCT exhibited a protective although not statistically significant effect on OS (hazard ratio=0.57 [0.32-1.02]). In conclusion, only one parameter (disease status before graft) remains risk factor for graft failure in this recent cohort.

Is there any impact of HLA-DPB1 disparity in 10/10 HLA-matched unrelated hematopoietic SCT? Results of a French multicentric retrospective study.

We retrospectively analyzed the impact of HLA-DPB1 mismatches in a large cohort of 1342 French patients who underwent 10/10 HLA-matched unrelated HSCT. A significant impact of HLA-DPB1 allelic mismatches (2 vs 0) was observed in severe acute GVHD (aGVHDIII-IV) (risk ratio (RR)=1.73, confidence interval (CI) 95% 1.09-2.73, P=0.019) without impact on OS, TRM, relapse and chronic GVHD (cGVHD). According to the T-cell epitope 3 (TCE3)/TCE4 HLA-DPB1 disparity algorithm, 37.6% and 58.4% pairs had nonpermissive HLA-DPB1, respectively. TCE3 and TCE4 disparities had no statistical impact on OS, TRM, relapse, aGVHD and cGVHD. When TCE3/TCE4 disparities were analyzed in the graft-vs-host or host-vs-graft (HVG) direction, only a significant impact of TCE4 nonpermissive disparities in the HVG direction was observed on relapse (RR=1.34, CI 95% 1.00-1.80, P=0.048). In conclusion, this French retrospective study shows an adverse prognosis of HLA-DPB1 mismatches (2 vs 0) on severe aGVHD and of nonpermissive TCE4 HVG disparities on relapse after HLA-matched 10/10 unrelated HSCT.

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.

[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.

Immune responses and vaccine-induced immunity against Porcine circovirus type 2.

Porcine circovirus type 2 (PCV2) is essential but not sufficient for postweaning multisystemic wasting syndrome (PMWS) occurrence in pigs. The outcome of PCV2 infection depends on the specific immune responses that are developing during the infection. Diseased pigs are immunosupressed and unable to mount effective immune responses to clear the virus from circulation. In the final stage, PMWS-affected pigs suffer from extensive lymphoid lesions and altered cytokine expression patterns in peripheral blood mononuclear cells (PBMCs) and lymphoid organs. PCV2 infection can also be asymptomatic, demonstrating that not every infection will guarantee the occurrence of severe immunopathological disturbances. Asymptomatic animals have higher virus specific and neutralising antibody titres than PMWS-affected animals. Recent results have pointed out that the mechanisms by which PCV2 can affect the immune responses involve the induction of IL-10, virus accumulation into and modulation of plasmacytoid dendritic cells and the role of viral DNA in regulation of immune cell functions. Fourteen years after the first description of PMWS in Canada, efficient commercial vaccines against PCV2 are available. The vaccine success is based on activated humoral and cellular immune responses against PCV2. This review focuses on the recent research on immunological aspects during PCV2 infections and summarizes what is currently known about the vaccine-induced immunity.

[Effectiveness of PRECEDE model for health education in metabolic control and reduction of cardiovascular risk factors in patients with diabetes type 2]. / Eficacia del modelo PRECEDE, de educación para la salud, en el control metabólico y de los factores de riesgo cardiovascular en pacientes con diabetes mellitus tipo 2.

OBJECTIVE: To evaluate the effectiveness of PRECEDE model for health education, in the metabolic control and the reduction of cardiovascular risk factors, in type 2 diabetic patients followed for over two years in primary health care services. MATERIALS AND METHODS: PRECEDE model for health education was used in 318 patients with type 2 diabetes, from five primary health care centres. The study was conducted during two years of monitoring. RESULTS: After two years of follow-up was observed decrease in diastolic and systolic pressures (p < 0.05), as well as in levels of total cholesterol and LDL-cholesterol (p < 0.05). Patients with good metabolic control (glycated hemoglobin A1c < 7% and LDL cholesterol < 100 mg/dl), increased from 9.9% to 16.8% (p < 0,05). On the other hand, 27% of patients improved their level of therapeutic adherence, and there was a decreased in the number of patients with microalbuminuria from 8.4% to 6.3% (p = 0.05). Finally, we found no differences in levels of glycated hemoglobin A1c, BMI and cardiovascular risk. Mortality after two years was 0.7%. DISCUSSION: PRECEDE model for health education is a useful method in the management of type 2 diabetes, that reduce the levels of blood pressure both systolic and diastolic, decrease the lipid levels, and improve the level of therapeutic adherence in type 2 diabetic patients, followed for two years.

[Domino transplantation of a living-donor kidney graft affected by thrombotic microangiopathy: surgical aspects]. / Transplantation domino à partir d'un donneur vivant d'un rein greffé atteint d'une micro-angiopathie thrombotique: aspects chirurgicaux.

We report surgical aspects of the first case of retransplantation of a kidney initially retrieved from a cadaveric donor, then on a first recipient which developed a recurrent severe and intractable thrombotic microangiopathy on the allograft.

[Mortality predictive factors of a clinical cohort of elderly patients]. / Factores predictores de mortalidad de una cohorte clínica de pacientes ancianos.

OBJECTIVE: To study the association between the main variables collected in the comprehensive geriatric assessment (CGA) and mortality, in a clinical cohort of elderly people referred from primary care, following standardised criteria, to a geriatric unit. Design. Retrospective cohort study. SETTING: Outpatient department of a geriatric unit of a hospital in Madrid, Spain. PARTICIPANTS: A total of 140 patients older than 65 years were followed up for 70 months. MAIN MEASUREMENTS: We collected demographic, clinical, functional, and social variables during the CGA carried out by a multidisciplinary team. After 70 months we measured this cohort survival and we analysed the predictive factors for mortality using Cox hazard ratio analysis. RESULTS. Sixty three patients died after the 70 months of the study, and the survival median was 37 months. In the univariate analysis, age, male gender, diagnosed cancer, COPD, the Katz and Lawton indices, and the Mini-Mental State Examination (MMSE) score of 35 items, were significantly associated with mortality. In the multivariate analysis we found, as predictive factors for mortality: MMSE-35 (HR=0.965; 95% CI, 0.934-0.998; P=.037); male gender (HR=2.75; 95% CI, 1.6-4.74; P=.001); Katz score (HR=1.22; 95% CI, 1.04-1.43; P=.017); Lawton score (HR=0.93; 95% CI, 0.82-1.07; P=.30). CONCLUSION: Cognitive impairment is a mortality predictive factor (HR=0.65), for each point less in the MMSE-35, we observed an increase in mortality risk of 3.5% (1-HR) at 70 months, after adjustment for Katz and Lawton index and gender.

A third renal transplantation: is it relevant and is it worth it?

INTRODUCTION: The aim of this retrospective study was to determine the outcome of third cadaveric renal transplantations performed between 1989 and 2004 among a cohort of 35 patients whose immunosuppression included induction therapy and calcineurin inhibitors. Most patients were highly sensitized with 1 (0-4) HLA (classes I + II) incompatibility between donor and recipient. RESULTS: The median follow-up time was 57 months (range, 1-190). Fourteen patients experienced delayed graft function that required posttransplantation hemodialysis. The current patient and graft survival rates were 91.4% and 82.8%, respectively. At last follow-up, 6 grafts had been lost: 1 due to primary nonfunction; 1 due to an urinary leak (day 45); 2 deaths with functioning grafts; and 2 chronic allograft nephropathies (CAN) at 85 and 60 months posttransplantation, respectively. Among the 10 patients who experienced acute rejection episodes, half were steroid-sensitive, whereas the others required OKT3 therapy. Overall, when excluding the 2 patients who presented with early loss of their grafts, 13 of 33 patients (39.4%) developed CAN, which led to the graft loss in only 2 cases. The mean creatinine clearance was 57 +/- 23 mL/min at year 5. Of the 35 recipients, 12 (34.3%) developed graft/perigraft complications, among whom 10 (83.3%) required treatment. The most frequent complication was lymphocele (M = 4; 11.4%) or infections that led to rehospitalization (n = 17). CONCLUSION: Results from third transplantations were encouraging. Thus, despite the organ shortage, a third graft was worth it!

IL-4 exacerbates disease in a Th1 cell transfer model of colitis.

IL-4 is associated with Th2-type immune responses and can either inhibit or, in some cases, promote Th1-type responses. We tested the effect of IL-4 treatment on the development of inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis, which has been characterized as a Th1-dependent disease. IL-4 treatment significantly accelerated the development of colitis in immunodeficient recipients (recombinase-activating gene-2 (Rag2)(-/-)) of CD4(+)CD45RB(high) T cells. Quantitative analysis of mRNA expression in the colons of IL-4-treated mice showed an up-regulation of both Th1- and Th2-associated molecules, including IFN-gamma, IP-10, MIG, CXCR3, chemokine receptor-8, and IL-4. However, cotreatment with either IL-10 or anti-IL-12 mAb effectively blocked the development of colitis in the presence of exogenous IL-4. These data indicate that IL-4 treatment exacerbates a Th1-mediated disease rather than induces Th2-mediated inflammation. As other cell types besides T cells express the receptor for IL-4, the proinflammatory effects of IL-4 on host cells in Rag2(-/-) recipients were assessed. IL-4 treatment was able to moderately exacerbate colitis in Rag2(-/-) mice that were reconstituted with IL-4Ralpha-deficient (IL-4Ralpha(-/-)) CD4(+)CD45RB(high) T cells, suggesting that the IL-4 has proinflammatory effects on both non-T and T cells in this model. IL-4 did not cause colitis in Rag2(-/-) mice in the absence of T cells, but did induce an increase in MHC class II expression in the lamina propria of the colon, which was blocked by cotreatment with IL-10. Together these results indicate that IL-4 can indirectly promote Th1-type inflammation in the CD4(+)CD45RB(high) T cell transfer model of colitis.