Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis.

Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6Chi-cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6Chi-cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.

Management of Hypertension in Patients With Diabetic Kidney Disease: Summary of the Joint Association of British Clinical Diabetologists and UK Kidney Association (ABCD-UKKA) Guideline 2021.

Diabetic kidney disease (DKD) accounts for >40% cases of chronic kidney disease (CKD) globally. Hypertension is a major risk factor for progression of DKD and the high incidence of cardiovascular disease and mortality in these people. Meticulous management of hypertension is therefore crucial to slow down the progression of DKD and reduce cardiovascular risk. Randomized controlled trial evidence differs in type 1 and type 2 diabetes and in different stages of DKD in terms of target blood pressure (BP). Renin-angiotensin blocking agents reduce progression of DKD and cardiovascular events in both type 1 and type 2 diabetes, albeit differently according to the stage of CKD. There is emerging evidence for the benefit of sodium glucose cotransporter 2, nonsteroidal selective mineralocorticoid antagonists, and endothelin-A receptor antagonists in slowing progression and reducing cardiovascular events in DKD. This UK guideline, developed jointly by diabetologists and nephrologists, has reviewed all available current evidence regarding the management of hypertension in DKD to produce a set of comprehensive individualized recommendations for BP control and the use of antihypertensive agents according to age, type of diabetes, and stage of CKD (https://ukkidney.org/sites/renal.org/files/Management-of-hypertension-and-RAAS-blockade-in-adults-with-DKD.pdf). A succinct summary of the guideline, including an infographic, is presented here.

Clinical practice guidelines for management of hyperglycaemia in adults with diabetic kidney disease.

A significant percentage of people with diabetes develop chronic kidney disease and diabetes is also a leading cause of end-stage kidney disease (ESKD). The term diabetic kidney disease (DKD) includes both diabetic nephropathy (DN) and diabetes mellitus and chronic kidney disease (DM CKD). DKD is associated with high morbidity and mortality, which are predominantly related to cardiovascular disease. Hyperglycaemia is a modifiable risk factor for cardiovascular complications and progression of DKD. Recent clinical trials of people with DKD have demonstrated improvement in clinical outcomes with sodium glucose co-transporter-2 (SGLT-2) inhibitors. SGLT-2 inhibitors have significantly reduced progression of DKD and onset of ESKD and these reno-protective effects are independent of glucose lowering. At the time of this update Canagliflozin and Dapagliflozin have been approved for delaying the progression of DKD. The Association of British Clinical Diabetologists (ABCD) and UK Kidney Association (UKKA) Diabetic Kidney Disease Clinical Speciality Group have undertaken a literature review and critical appraisal of the available evidence to inform clinical practice guidelines for management of hyperglycaemia in adults with DKD. This 2021 guidance is for the variety of clinicians who treat people with DKD, including GPs and specialists in diabetes, cardiology and nephrology.

Incidence, Risk Factors, and Effect on Allograft Survival of Glomerulonephritis Post-transplantation in a United Kingdom Population: Cohort Study.

Background: Post-transplant glomerulonephritis (PTGN) has been associated with inferior long-term allograft survival, and its incidence varies widely in the literature. Methods: This is a cohort study of 7,623 patients transplanted between 2005 and 2016 at four major transplant UK centres. The diagnosis of glomerulonephritis (GN) in the allograft was extracted from histology reports aided by the use of text-mining software. The incidence of the four most common GN post-transplantation was calculated, and the risk factors for disease and allograft outcomes were analyzed. Results: In total, 214 patients (2.8%) presented with PTGN. IgA nephropathy (IgAN), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), and membranoproliferative/mesangiocapillary GN (MPGN/MCGN) were the four most common forms of post-transplant GN. Living donation, HLA DR match, mixed race, and other ethnic minority groups were associated with an increased risk of developing a PTGN. Patients with PTGN showed a similar allograft survival to those without in the first 8 years of post-transplantation, but the results suggest that they do less well after that timepoint. IgAN was associated with the best allograft survival and FSGS with the worst allograft survival. Conclusions: PTGN has an important impact on long-term allograft survival. Significant challenges can be encountered when attempting to analyze large-scale data involving unstructured or complex data points, and the use of computational analysis can assist.

Frequency and predictive validity of olfactory and taste dysfunction in patients with SARS-CoV-2 infection.

BACKGROUND AND OBJECTIVE: Olfactory and taste dysfunction (OD, TD) have been considered symptoms of SARS-CoV-2 infection. However, its presence in certain populations, especially those with mild clinical symptoms, has not been clarified. The objective was to estimate the frequency of OD and TD, and its predictive validity in patients detected in Primary Care. PATIENTS AND METHODS: A cross-sectional study was carried out in the Spanish National Health System. An epidemiological survey was administered to patients who were requested the PCR test for SARS-CoV-2. Odds ratio (OR) were estimated to measure the magnitude of the association between OD and TD and the existence of SARS-CoV-2 infection. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of these symptoms in SARS-CoV-2 infection were calculated. RESULTS: Of 1038 patients screened, 20.1% had SARS-CoV-2 infection. OD and DG were present in 64.4% (95% CI 56.0-72.1) and 56.2% (95% CI 47.9-64.2) of the subjects with infection, respectively. The OR for OD was 12.2 (95% CI 8.26-18.06) and for TD was 7.95 (95% CI 5.48-11.53). TD presented a sensitivity of 41.1% (95% CI 34.4-46.1), a specificity of 91.9% (95% CI 89.8-93.7), a PPV of 56.2% (95% CI48.0-64.2) and a NPV of 86.1% (95% CI 83.6-88.3), while the OD showed a sensitivity of 45.0% (95% CI 37.6-51.5), a specificity of 93.7% (95% CI 91.8-95.0), a PPV of 64.4% (95% CI 56.0-72.1) and a NPV of 87.1% (95% CI 84.7-89.2). CONCLUSIONS: More than half of the subjects with SARS-CoV-2 infection have OD or TD. The presence of OD or TD could be of diagnostic utility due to its ability to predict infection in more than half of the cases.

ANTECEDENTES Y OBJETIVO: La disfunción olfatoria (DO) y gustativa (DG) han demostrado ser síntomas de la infección por SARS-CoV-2. Sin embargo, su presencia en determinadas poblaciones, sobre todo en aquellas con cuadros clínicos leves, aún debe aclararse. El objetivo fue estimar la frecuencia de DO y DG, y su validez predictiva en pacientes detectados en Atención Primaria. PACIENTES Y MÉTODOS: Se realizó un estudio transversal en el Sistema Nacional de Salud español. Se administró una encuesta epidemiológica dirigida a pacientes a los que se les solicitó la prueba PCR para SARS-CoV-2. Se estimaron las odds ratio (OR) para medir la magnitud de la asociación entre la DO y DG y la existencia de infección por SARS-CoV-2. Se calculó la sensibilidad, la especificidad y los valores predictivos positivos (VPP) y negativos (VPN) de estos síntomas en la infección por SARS-CoV-2. RESULTADOS: Se captaron 1.038 pacientes, de los cuales el 20,1% presentaban infección por SARS-CoV-2. Las DO y DG estuvieron presentes en el 64,4% (IC 95% 56,0­72,1) y el 56,2% (IC 95% 47,9­64,2) de los sujetos con infección, respectivamente. La OR para la DO fue de 12,2 (IC 95% 8,26−18,06) y para la DG de 7,95 (IC 95% 5,48−11.53). La DG presentó una sensibilidad del 41,1% (IC 95% 34,4­46,1), una especificidad del 91,9% (IC 95% 89,8­93,7), un VPP del 56,2% (IC 95% 48,0­64,2) y un VPN de 86,1% (IC 95% 83,6­88,3), mientras que la DO mostró una sensibilidad del 45,0% (IC 95% 37,6­51,5), una especificidad del 93,7% (IC 95% 91,8­95,0), un VPP del 64,4% (IC 95% 56,0­72,1) y un VPN del 87,1% (IC 95% 84,7­89,2). CONCLUSIONES: Más de la mitad de los sujetos con infección por SARS-CoV-2 presentan DO o DG. La presencia de DO o de DG podría ser de utilidad diagnostica por su capacidad para predecir la infección en más de la mitad de las ocasiones.

[Frequency and predictive validity of olfactory and taste dysfunction in patients with SARS-CoV-2 infection]. / Frecuencia de aparición y validez predictiva de la disfunción olfatoria y del gusto en pacientes con infección por SARS-CoV-2.

BACKGROUND AND OBJECTIVE: Olfactory and taste dysfunction (OD, TD) have been considered symptoms of SARS-CoV-2 infection. However, its presence in certain populations, especially those with mild clinical symptoms, has not been clarified. The objective was to estimate the frequency of OD and TD, and its predictive validity in patients detected in Primary Care. PATIENTS AND METHODS: A cross-sectional study was carried out in the Spanish National Health System. An epidemiological survey was administered to patients who were requested the PCR test for SARS-CoV-2. Odds ratio (OR) were estimated to measure the magnitude of the association between OD and TD and the existence of SARS-CoV-2 infection. The sensitivity, specificity, and positive and negative predictive values (PPV, NPV) of these symptoms in SARS-CoV-2 infection were calculated. RESULTS: Of 1,038 patients screened, 20.1% had SARS-CoV-2 infection. OD and DG were present in 64.4% (95% CI 56.0-72.1) and 56.2% (95% CI 47.9-64.2) of the subjects with infection, respectively. The OR for OD was 12.2 (95% CI 8.26-18.06) and for TD was 7.95 (95% CI 5.48-11.53). TD presented a sensitivity of 41.1% (95% CI 34.4-46.1), a specificity of 91.9% (95% CI 89.8-93.7), a PPV of 56.2% (95% CI48.0-64.2) and a NPV of 86.1% (95% CI 83.6-88.3), while the OD showed a sensitivity of 45.0% (95% CI 37.6-51.5), a specificity of 93.7% (95% CI 91.8-95.0), a PPV of 64.4% (95% CI 56.0-72.1) and a NPV of 87.1% (95% CI 84.7-89.2). CONCLUSIONS: More than half of the subjects with SARS-CoV-2 infection have OD or TD. The presence of OD or TD could be of diagnostic utility due to its ability to predict infection in more than half of the cases.

[Clinical and epidemiological characteristics of SARS-CoV-2 infections in family physicians: A case-control study]. / Características clínico-epidemiológicas de la infección por el virus SARS-CoV-2 en médicos de familia: un estudio de casos y controles.

OBJECTIVE: To identify the sociodemographic, clinical and epidemiological characteristics associated with the presence of infection by the SARS-CoV-2 virus in family physicians who carry out their work in Primary Care (PC) or in Hospital Emergencies. DESING: Observational analytical case-control study. SITE: Primary care. PARTICIPANTS: 969 Primare Care Physicians, Hospital Emergency physicians and other extrahospitalry centers that had PCR for the detection of the SARS-CoV-2. Of these, 133 participated as cases (PCR positive) and 836 as controls (PCR negative). INTERVENTIONS: No. MAIN MEASUREMENTS: Sociodemographic and work, contact with a COVID-19 patient, symptoms present during the process, first manifested symptom, previous chronic pathologies, and tobacco use. RESULTS: 13.7% (95% CI: 11.6-16.0) were cases infected with SARS-CoV-2. The most frequently declared symptoms by those infected were a feeling of fatigue/tiredness (69.2%; 95% CI: 60.9-77.4%), cough (56.4%; 95% CI: 47.6-65.2%) and headache (55.6%; 95% CI: 46.8-64.4%).Using logistic regression, the variables independently associated with SARS-CoV-2 virus infection in Family Physicians were: previous contact with a COVID-19 patient (OR: 2.3; 95% CI: 1.2-4.2), present fatigue / tiredness (OR: 2.2; 95% CI: 1.2-3.9), smell alteration (4.6; 95% CI: 1.7-12.5), taste alteration (OR: 32.0; 95% CI: 9.6-106.8), cough (OR: 3.0; 95% CI: 1.7-5.3) and fever (OR: 6.1; 95% CI: 3.2-11.4). CONCLUSIONS: Symptoms independently related to SARS-CoV-2 virus infection in Family Physicians were fatigue, fever, cough, and altered taste and smell. The presence of these symptoms could facilitate the diagnosis of suspected COVID-19 disease and the earlier selection of those that require confirmatory tests.

Association of British Clinical Diabetologists and Renal Association guidelines on the detection and management of diabetes post solid organ transplantation.

Post-transplant diabetes mellitus (PTDM) is common after solid organ transplantation (SOT) and associated with increased morbidity and mortality for allograft recipients. Despite the significant burden of disease, there is a paucity of literature with regards to detection, prevention and management. Evidence from the general population with diabetes may not be translatable to the unique context of SOT. In light of emerging clinical evidence and novel anti-diabetic agents, there is an urgent need for updated guidance and recommendations in this high-risk cohort. The Association of British Clinical Diabetologists (ABCD) and Renal Association (RA) Diabetic Kidney Disease Clinical Speciality Group has undertaken a systematic review and critical appraisal of the available evidence. Areas of focus are; (1) epidemiology, (2) pathogenesis, (3) detection, (4) management, (5) modification of immunosuppression, (6) prevention, and (7) PTDM in the non-renal setting. Evidence-graded recommendations are provided for the detection, management and prevention of PTDM, with suggested areas for future research and potential audit standards. The guidelines are endorsed by Diabetes UK, the British Transplantation Society and the Royal College of Physicians of London. The full guidelines are available freely online for the diabetes, renal and transplantation community using the link below. The aim of this review article is to introduce an abridged version of this new clinical guideline ( https://abcd.care/sites/abcd.care/files/site_uploads/Resources/Position-Papers/ABCD-RA%20PTDM%20v14.pdf).

[Hereditary breast and ovarian cancer syndrome: Diagnosis and therapeutic implications]. / Syndrome héréditaire de prédisposition au cancer du sein et de l'ovaire : diagnostic et implications thérapeutiques.

Patients who carry the BReast Cancer 1 or 2 (BRCA) gene mutations have an underlying hereditary predisposition for breast and ovarian cancers. These deleterious genetic mutations are the most common ones implicated in hereditary breast and ovarian cancers. Oncogenetic counselling plays a key role in identifying patient for BRCA testing and for mutation identification. BRCA1/2 carriers have to be followed up regularly and may justify breast and/or adnexal prophylactic surgery, according to the French National Cancer Institute guidelines (INCa). Poly- (DNA-riboses) polymerases inhibitors, notably olaparib, have a major role in the management of epithelial ovarian cancer in patients with BRCA mutation and many studies are ongoing to expand their indications in a near future.

Clinical-pathological correlations in post-transplant thrombotic microangiopathy.

AIMS: Post-transplant thrombotic microangiopathy (TMA) is a rare and clinically challenging finding in renal transplant biopsies. In addition to recurrent atypical haemolytic uraemic syndrome, TMA in renal transplants is associated with various conditions, such as calcineurin inhibitor (CNI) treatment, antibody-mediated rejection (ABMR), viral infections, sepsis, pregnancy, malignancies, and surgery. The therapeutic implications of this diagnosis are considerable. In order to better understand post-transplant TMA and to identify histological or clinical differences between associated causes, we conducted a multicentre retrospective study. METHODS AND RESULTS: Clinical parameters and transplant renal biopsy findings from 81 patients with TMA were analysed. Biopsies from 38 patients were also analysed with electron microscopy. On the basis of clinical-pathological correlation, TMA was attributed to a main aetiology, whenever possible. TMA occurred at a median of 30 days post-transplantation. Systemic features of TMA were present in only 18% of cases. Twenty-two per cent of cases were attributed to CNI and 11% to ABMR. Although other potentially contributing factors were found in 56% of patients, in most cases (63%) no clearly attributable cause of TMA was identified. Histological differences between groups were minimal. The detection of ultrastructural features that are usually associated with ABMR may help to establish ABMR as the cause of TMA. CONCLUSIONS: Although CNI and ABMR appear to be the main contributors to post-transplant TMA, the aetiology of most cases is probably multifactorial, and TMA cannot be unequivocally attributed to a single underlying aetiology. Morphological features of TMA are not discriminating, but electron microscopy may help to identify ABMR-associated TMA.

Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples.

BACKGROUND: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage. METHODS: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study. To account for post-transplantation changes unrelated to rejection, we generated time-adjusted gene-expression residuals from linear mixed-effects models in stable patients. To select genes, we used penalised logistic regression based on 27 stable patients and 27 rejectors with biopsy-proven T-cell-mediated rejection, fulfilling strict inclusion/exclusion criteria. We validated this signature in i) an independent group of stable patients and patients with concomitant T-cell and antibody-mediated-rejection, ii) patients from an independent study, iii) cross-sectional pre-biopsy samples from non-rejectors and iv) longitudinal follow-up samples covering the first post-transplant year from rejectors, non-rejectors and stable patients. FINDINGS: A parsimonious TCMR-signature (IFNG, IP-10, ITGA4, MARCH8, RORc, SEMA7A, WDR40A) showed cross-validated area-under-ROC curve 0.84 (0.77-0.88) (median, 2.5th-97.5th centile of fifty cross-validation cycles), sensitivity 0.67 (0.59-0.74) and specificity 0.85 (0.75-0.89). The estimated probability of TCMR increased seven weeks prior to the diagnostic biopsy and decreased after treatment. Gene expression in all patients showed pronounced variability, with up to 24% of the longitudinal samples in stable patients being TCMR-signature positive. In patients with borderline changes, up to 40% of pre-biopsy samples were TCMR-signature positive. INTERPRETATION: Molecular marker alterations in blood emerge well ahead of the time of clinically overt TCMR. Monitoring a TCMR-signature in peripheral blood could unravel T-cell-related pro-inflammatory activity and hidden immunological processes. This additional information could support clinical management decisions in cases of patients with stable but poor kidney function or with inconclusive biopsy results.

Defining Phenotypes in Diabetic Nephropathy: a novel approach using a cross-sectional analysis of a single centre cohort.

The global increase in Diabetes Mellitus (DM) has led to an increase in DM-Chronic Kidney Disease (DM-CKD). In this cross-sectional observational study we aimed to define phenotypes for patients with DM-CKD that in future may be used to individualise treatment We report 4 DM-CKD phenotypes in 220 patients recruited from Imperial College NHS Trust clinics from 2004-2012. A robust principal component analysis (PCA) was used to statistically determine clusters with phenotypically different patients. 163 patients with complete data sets were analysed: 77 with CKD and 86 with DM-CKD. Four different clusters were identified. Phenotypes 1 and 2 are entirely composed of patients with DM-CKD and phenotypes 3 and 4 are predominantly CKD (non-DM-CKD). Phenotype 1 depicts a cardiovascular phenotype; phenotype 2: microvascular complications with advanced DM-CKD; phenotype 3: advanced CKD with less anaemia, lower weight and HbA1c; phenotype 4: hypercholesteraemic, younger, less severe CKD. We are the first group to describe different phenotypes in DM-CKD using a PCA approach. Identification of phenotypic groups illustrates the differences and similarities that occur under the umbrella term of DM-CKD providing an opportunity to study phenotypes within these groups thereby facilitating development of precision/personalised targeted medicine.

CCL18 synergises with high concentrations of glucose in stimulating fibronectin production in human renal tubuloepithelial cells.

BACKGROUND: Diabetic nephropathy is the leading cause of end stage kidney disease worldwide. The pathogenesis of this disease remains elusive and multiple factors have been implicated. These include the effects of hyperglycaemia, haemodynamic and metabolic factors, and an inflammatory process that stimulates cellular signalling pathways leading to disease progression and severe fibrosis. Fibronectin (Fn) is an important protein of the extracellular matrix that is essential in fibrosis and its presence in increased amounts has been identified in the kidney in diabetic nephropathy. METHODS: Proximal tubuloepithelial (HK-2) cells were stimulated with high glucose (30 mM D-glucose) or glycated albumin (500 µg/mmol) + 4 mM D-glucose or their controls, Mannitol (26 mM + 4 mM D-glucose) and 4 mM D-glucose, respectively. Following 48 h of stimulation the supernatant was collected and MTT [3-(4,5-dimethylthiazole-2,5-diphenyltetrazolium bromide] assay performed to assess cell viability. HK-2 cells were also stimulated in the above environments with recombinant CCL18 (rCCL18) or MCP-1 (rMCP-1) for 48 h with quantification of Fn levels using ELISA. RESULTS: Co-stimulation of HK-2 cells with high concentrations of glucose and rCCL18 significantly increased Fn (p < 0.001), in comparison to high concentrations of glucose alone. HK-2 cells stimulated with glycated albumin consistently produced Fn and this did not alter following co-stimulation with rCCL18 or rMCP-1. CONCLUSION: This study demonstrates how stimulation with a specific chemokine CCL18 in high glucose upregulates the production of Fn from proximal tubuloepithelial cells. This may be relevant to the development of renal fibrosis in diabetic nephropathy.

Guillain-Barré syndrome following the 2009 pandemic monovalent and seasonal trivalent influenza vaccination campaigns in Spain from 2009 to 2011: outcomes from active surveillance by a neurologist network, and records from a country-wide hospital discharge database.

BACKGROUND: Studies have shown a slight excess risk in Guillain-Barré syndrome (GBS) incidence associated with A(H1N1)pdm09 vaccination campaign and seasonal trivalent influenza vaccine immunisations in 2009-2010. We aimed to assess the incidence of GBS as a potential adverse effect of A(H1N1)pdm09 vaccination. METHODS: A neurologist-led network, active at the neurology departments of ten general hospitals serving an adult population of 4.68 million, conducted GBS surveillance in Spain in 2009-2011. The network, established in 1996, carried out a retrospective and a prospective study to estimate monthly alarm thresholds in GBS incidence and tested them in 1998-1999 in a pilot study. Such incidence thresholds additionally to observation of GBS cases with immunisation antecedent in the 42 days prior to clinical onset were taken as alarm signals for 2009-2011, since November 2009 onwards. For purpose of surveillance, in 2009 we updated both the available centres and the populations served by the network. We also did a retrospective countrywide review of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis from January 2009 to December 2011. RESULTS: Among 141 confirmed of 148 notified cases of GBS or Miller-Fisher syndrome, Brighton 1-2 criteria in 96 %, not a single patient was identified with clinical onset during the 42-day time interval following A(H1N1)pdm09 vaccination. In contrast, seven cases were seen during a similar period after seasonal campaigns. Monthly incidence figures did not, however, exceed the upper 95 % CI limit of expected incidence. A retrospective countrywide review of the registry of hospital-discharged patients having ICD-9-CM code 357.0 (acute infective polyneuritis) as their principal diagnosis did not suggest higher admission rates in critical months across the period December 2009-February 2010. CONCLUSIONS: Despite limited power and underlying reporting bias in 2010-2011, an increase in GBS incidence over background GBS, associated with A(H1N1)pdm09 monovalent or trivalent influenza immunisations, appears unlikely.

Staged Hand-Assisted Bilateral Native Nephrectomy for Management of Posttransplant Polyuria in an Adult with Dent's Disease.

Polyuria after kidney transplantation causes graft dysfunction and increased thrombotic risk. We present a case of a polyuric adult with Dent's disease who underwent staged bilateral native nephrectomies, the first operation before transplant and the second four months after transplant. This led to improved allograft function maintained during four years of follow-up. The retroperitoneal laparoscopic approach was well tolerated and allowed continuation of peritoneal dialysis before transplantation. A staged approach helps regulate fluid balance perioperatively and may be tailored to individual need according to posttransplant urine output. This novel approach should be considered for polyuric patients with tubular dysfunction including Dent's disease.

Factores asociados a la Tricomoniosis, Hospital de Apoyo de San Francisco, Ayacucho 2002 / Factors associated with trichomoniasis, Hospital de Apoyo de San Francisco, Ayacucho 2002

Objetivo: conocer los factores asociados a la tricomoniosis en mujeres que acudieron al servicio al Hospital de Apoyo de San Francisco. Métodos: se incluyeron mujeres usuarias del servicio de Obstetricia- Planificación Familiar, a quienes se solicito consentimiento verbal previo a la toma de muestra. Se recogió una muestra de secreción vaginal con hisopo estéril, previa colocación de un espéculo estéril, midiendo el pH con tiras reactivas. La identificación de Trichomonas vaginalis se realizó por observación directa de la muestra (por triplicado), con objetivos de 100X y 400X. Los factores asociados fueron recolectados en fichas ad-hoc. Resultados: se incluyeron 196 mujeres que asistieron al servicio de Obstetricia-Planificación familiar entre julio y agosto del 2002. Se obtuvo una frecuencia de tricomoniosis de 19.9%, 7.2% en solteras, 8.7% en mujeres con primaria incompleta, 9.2% en amas de casa, 4.5% en trabajadoras sexuales, 9.7% en mujeres que reportaban dos parejas sexuales, 16.3% en las que realizaban el coito semanalmente, 12.8% en las que realizan la higiene genital diariamente, 11.7% en las que usan agua y jabón, 13.3% en las que usan anticonceptivos y 9.7% cuando el pH se encontraba entre 5.6 y 6. Conclusión: existe una alta frecuencia de tricomoniasis en las mujeres estudiadas, asociada a los factores de riesgo conocidos, aunque en nuestro trabajo no se encontró en ningún caso asociación estadísticamente significativa.

Objective: To determine the factors associated with trichomoniasis in women who attended the Hospital de Apoyo in San Francisco. Methods: We included women who attended to the Obstetrics and Family Planning consulting room, who were requested verbal consent prior to sampling. A sample of vaginal secretion was collected with sterile swab, after placing a sterile speculum, measuring the pH test with strips. Identification of Trichomonas vaginalis was performed by direct observation of the sample (in triplicate) with 100X and 400X objectives. The associated factors were collected by ad-hoc questionnaires. Results: We included 196 women who attended to the Obstetrics and Family Planning consulting room. We obtained a frequency of Trichomoniasis of 19.9%, being 7.2% single, 8.7% women with incomplete primary education, 9.2% housewives, 4.5% sex workers, 9.7% women who reported two sexual partners, 16.3% those performing weekly intercourse, 12.8% engaged in daily genital hygiene, 11.7% those using soap and water, 13.3% those using contraceptives and 9.7% when the pH was between 5.6 and 6. Conclusion: There is a high frequency of trichomoniasis in women studied, associated with known risk factors, although our work could not find in any statistically significant association.

Dermatofitosis en estudiantes de la Institución Educativa "San Juan de la Frontera", Ayacucho, Perú, 2010 / Dermatophytosis among children of San Juan de la Frontera School, Ayacucho, Peru, 2010

Objetivo: Conocer la frecuencia de la dermatofitosis en los estudiantes de la Institución Educativa ôSan Juan de la Fronteraõ del Asentamiento Humano ôJuan Velasco Alvaradoõ, Ayacucho. Métodos: Se estudió a los estudiantes matriculados en el año escolar 2010 en la IE ôSan Juan de la Fronteraõ. Fueron incluidos todos los estudiantes con signos de micosis superficial. Se ubicaron las zonas afectadas y se desinfectaron con alcohol, con un bisturí desinfectado se raspó suavemente para quitar las escamas los que fueron colocadas en sobres de papel oscuro. Las muestras de los espacios interdigitales se tomaron con ayuda de una torunda estéril. Se realizó el examen directo en la lámina porta objetos con KOH al 10%. Las muestras se cultivaron en placas petri conteniendo agar Sabouraud, se incubaron a 25ºC por 15 días. Se identificó con base en las características macroscópicas y microscópicas de las colonias. Resultados: Se halló una frecuencia de 68% de dermatofitosis, 47% en muestras de los espacios interdigitales, 61.8% en niños que crían animales domésticos, 88.2% en aquellos cuyo piso de la vivienda es de tierra, no se encontró diferencia por género. Conclusiones: Concluimos que la dermatofitosis en un problema muy frecuente en los estudiantes de la Institución Educativa ôSan Juan de la Fronteraõ, la zona anatómica más afectada fue el espacio interdigital y la especie más aislada T. mentagrophytes.

Objective: Knowing the frequency of dermatophytosis in students of School San Juan de la Frontera from the slum ôJuan Velasco Alvaradoõ,Ayacucho. Methods: Population: Students enrolled in the school year 2010 in the San Juan de la Frontera School. Sample Size: Included all students with signs of superficial mycoses. Biological sample collection: Affected areas were located and disinfected with alcohol, with a disinfected scalpel gently scraped to remove the scales that were placed in brown paper envelopes. Samples of the interdigital spaces were taken using a sterile swab. It was held in the sheet glass slide with 10% KOH. The samples were cultured in petri dishes containing Sabouraud agar, incubated at 25 ° C for 15 days. Was made based on macroscopic and microscopic characteristics of the colonies. Results: We found a frequency of 68% of dermatophytosis, 47% in samples from the interdigital spaces, 61.8% for children who raise pets, 88.2% in those whose house floor is dirt, there was no difference gender. Dermatophytosis conclude that a very common problem among students of San Juan de la Frontera School, the anatomic area most affected was the interdigital space, the most commonly isolated T. mentagrophytes.

The D category VI type 4 allele is prevalent in the Spanish population.

BACKGROUND: The D category VI (DVI) is one of the clinically most important partial D. Three different molecular structures causing the DVI phenotype have been described. STUDY DESIGN AND METHODS: To determine the molecular basis of the DVI phenotype in the Spanish population, 20 DVI samples, previously detected in serologic screening, were examined by polymerase chain reaction with RHD exon-specific primers. Unexpected findings were further pursued by cDNA nucleotide sequencing. RESULTS: A novel pattern of RHD exon amplification was detected, which did not correspond to any of the previously described molecular structures. The cDNA sequence led to the identification of the new hybrid RHD-Ce(3-5)-D allele. The origin of exon 2 is undeterminable, because the 5' breakpoint was located within a region of RHD and RHCE identical sequence, which encompasses this exon. Sequencing of intron 5 allowed the 3' breakpoint to be mapped between the sixth and seventh polymorphic sites. Serologically, the hybrid protein has a D epitope expression pattern identical to the previously described DVI phenotypes and an antigen density slightly lower than DVI type 3. The new DVI variant is linked to the DCe haplotype and expresses the low-incidence BARC antigen. CONCLUSION: A novel structure causing the DVI phenotype, here named DVI type 4, has been characterized. This novel structure is the most frequent cause of DVI in Spain.

Amyloid-beta peptide is toxic to neurons in vivo via indirect mechanisms.

We have studied the neurotoxicity of amyloid-beta (Abeta) after a single unilateral intravitreal injection. Within the retina apoptotic cells were seen throughout the photoreceptor layer and the inner nuclear layer but not in the ganglion cell layer at 48 h after injection of Abeta(1-42) compared to vehicle control and control peptide. At 5 months, there was a significant reduction in total cell numbers in the ganglion cell layer in Nissl stained retinas. There was glial cell dysfunction with upregulation of glial fibrillary acidic protein and a reduction in the expression of Müller cell associated proteins in the injected retinas. These results suggest an indirect cytotoxic effect of Abeta on retinal neurons and an important role for dysfunction of Müller glia in mediating Abeta neurotoxicity.