Phenotypic characterization of a pediatric cohort with cystinuria and usefulness of newborn screening.

BACKGROUND: Cystinuria is an inherited metabolic disease involving the defective transport of cystine and the dibasic amino acids in the renal proximal tubules that causes the formation of stones in the urinary system. In our regional child health program, cystinuria is included in newborn metabolic screening. Our objectives are the phenotypic characterization of our cystinuric pediatric cohort and to present our experience in neonatal cystinuria screening. METHODS: The study of clinical cases of pediatric patients diagnosed with cystinuria over a period of 32 years. All patients were studied at demographic, clinical, laboratory, radiological, and therapeutic levels. RESULTS: We diagnosed 86 pediatric patients with cystinuria; 36% of them had the homozygous biochemical phenotype. 95.3% of the patients were detected by neonatal metabolic screening. We performed urine biochemical analyses of parents with additional diagnoses of 63 adult patients. The mean follow-up time was 16.8 ± 8.5 years. 11.6% of patients developed one or more episodes of urinary tract infection during that period. Chronic kidney disease, proteinuria, and hypertension were uncommon (1.2%). 10.5% developed kidney stones at the mean age of presentation of 7.78 ± 7.6 years; 33% were recurrent. The risk of developing lithiasis was higher for homozygous biochemical-phenotype patients. Hypercalciuria was a significant risk factor in the development of lithiasis. CONCLUSIONS: Our clinical data suggest that diagnosing cystinuria through neonatal screening could be a useful strategy for the detection of presymptomatic cases, in order to establish preventive measures, as well as for the detection of relatives at risk. A higher resolution version of the Graphical abstract is available as Supplementary information.

A Th2-score in the tumor microenvironment as a predictive biomarker of response to Bacillus Calmette Guérin in patients with non-muscle invasive bladder carcinoma: A retrospective study.

Intravesical Bacillus Calmette Guerin (BCG) is the gold standard therapy for intermediate/high-risk non-muscle invasive bladder cancer (NMIBC). However, the response rate is ~60%, and 50% of non-responders will progress to muscle-invasive disease. BCG induces massive local infiltration of inflammatory cells (Th1) and ultimately cytotoxic tumor elimination. We searched for predictive biomarker of BCG response by analyzing tumor-infiltrating lymphocyte (TIL) polarization in the tumor microenvironment (TME) in pre-treatment biopsies. Pre-treatment biopsies from patients with NMIBC who received adequate intravesical instillation of BCG (n = 32) were evaluated retrospectively by immunohistochemistry. TME polarization was assessed by quantifying the T-Bet+ (Th1) and GATA-3+ (Th2) lymphocyte ratio (G/T), and the density and degranulation of EPX+ eosinophils. In addition, PD-1/PD-L1 staining was quantified. The results correlated with BCG response. In most non-responders, Th1/Th2 markers were compared in pre-and post-BCG biopsies. ORR was 65.6% in the study population. BCG responders had a higher G/T ratio and a greater number of degranulated EPX+ cells. Variables combined into a Th2-score showed a significant association with higher scores in responders (p = 0.027). A Th2-score cut-off value >48.1 allowed discrimination of responders with 91% sensitivity but lower specificity. Relapse-free survival was significantly associated with the Th2-score (p = 0.007). In post-BCG biopsies from recurring patients, TILs increased Th2-polarization, probably reflecting BCG failure to induce a pro-inflammatory status and, thus, a lack of response. PD-L1/PD-1 expression was not associated with the response to BCG. Our results support the hypothesis that a pre-existing Th2-polarized TME predicts a better response to BCG, assuming a reversion to Th1 polarization and antitumor activity.

A Newborn Screening Program for Sickle Cell Disease in Murcia (Spain).

Sickle cell disease (SCD) is an inherited autosomal recessive hemoglobin disorder caused by the presence of hemoglobin S, a mutant abnormal hemoglobin caused by a nucleotide change in codon 6 of the ß-globin chain gene. SCD involves a chronic inflammatory state, exacerbated during vaso-occlusive crises, which leads to end-organ damage that occurs throughout the lifespan. SCD is associated with premature mortality in the first years of life. The process of sickling provokes asplenia in the first years of life with an increased risk of infection by encapsulated germs. These complications can be life-threatening and require early diagnosis and management. The most important interventions recommend an early diagnosis of SCD to ensure that affected newborns receive immediate care to reduce mortality and morbidity. The newborn screening program in the region of Murcia for SCD began in March 2016. We aimed to determine the incidence of sickle cell anemia and other structural hemoglobinopathies in the neonatal population of the region of Murcia, an area of high migratory stress, and to systematically assess the benefit of newborn screening for SCD, leading to earlier treatment, as well as to offer genetic counseling to all carriers. The prevalence of SCD in our region is similar to others in Spain, except for Catalonia and Madrid. The newborns with confirmed diagnoses of SCD received early attention, and all the carriers received genetic counseling.

Comparison of the simple cyclic voltammetry (CV) and DPPH assays for the determination of antioxidant capacity of active principles.

Antioxidant activity of a number of small (low molecular weight) natural compounds found in spices, condiments or drugs (gallic acid, sesamol, eugenol, thymol, carvacrol, vanillin, salicylaldehyde, limonene, geraniol, 4-hexylresorcinol, etc.) has been evaluated using electrochemical and DPPH• radical scavenging measurements. Structural analysis of the tested compound suggest a remarkable activity for phenol derivatives and the importance of the -R groups located on the phenolic ring in the molecule's ability to act as free radical scavenging as well as their influence in the electrochemical behavior. The voltammetric method can be used for the determination of the antioxidant capability in the same manner as the DPPH• radical scavenging because of the correlation found between oxidation potentials and anti-radical power (ARP = 1/EC50). Such electrochemical determination is fast and cheap and allows making measurements under a variety of experimental conditions. The accuracy of the electrochemical measurements is the same for all the compounds, irrespective of their scavenging activity, the opposite of what occurs in the DPPH• test.

MDCT of abdominal wall lumbar hernias: anatomical review, pathologic findings and differential diagnosis.

PURPOSE: To review the anatomical landmarks of the abdominal wall lumbar region and its normal appearance on multidetector computed tomography (MDCT) and to briefly describe the MDCT features of lumbar hernias. METHODS: We performed a retrospective search of the imaging report database from November 2007 to October 2011. We retrieved the clinical data and MDCT studies of patients suffering from abdominal wall lumbar hernias. We reviewed the imaging features of abdominal lumbar hernias and compared those with the normal appearance of the lumbar region in asymptomatic individuals. RESULTS: We classified lumbar wall hernias as diffuse, superior (or Grynfelt-Lesshaft) and inferior (or Petit) lumbar hernias. We briefly describe the imaging features of each subtype and review the anatomy and MDCT appearance of normal lumbar region. CONCLUSIONS: Currently available MDCT provides an excellent opportunity for reviewing the normal anatomy of the wall lumbar region and may be considered a useful modality for evaluating lumbar hernias.

MDCT of variations and anomalies of the neural arch and its processes: part 1--pedicles, pars interarticularis, laminae, and spinous process.

OBJECTIVE: The purpose of this pictorial essay is to review the anatomic variations and congenital anomalies of the neural arch and its processes as seen on MDCT images of the spine. CONCLUSION: Variations and anomalies of the pedicles, pars interarticularis, laminae, and spinous processes may be readily identified on MDCT studies. Familiarity with their MDCT appearances is required for characterization and differential diagnosis and may help assess their potential clinical relevance.

MDCT of variations and anomalies of the neural arch and its processes: part 2--articular processes, transverse processes, and high cervical spine.

OBJECTIVE: The purpose of this pictorial essay is to review the variations and anomalies of the neural arch and its processes with a focus on the articular and transverse processes. We also discuss variations and anomalies of the neural arch at the high cervical spine. CONCLUSION: Variations and anomalies of the neural arch and its processes may be identified on MDCT studies. Familiarity with their MDCT appearances is required for characterization and may help evaluate their potential clinical relevance.

Synovial plicae of the hip: evaluation using MR arthrography in patients with hip pain.

OBJECTIVE: The appearance and distribution of the intra-articular plicae of the hip have been addressed in few reports in the anatomic and radiological literature. This study aims to determine the prevalence of visible synovial hip plicae using MR arthrography and to measure the association of visible synovial hip plicae with MR arthrographic diagnosis of labral tears, femoroacetabular impingement, and osteoarthritis. MATERIALS AND METHODS: Following institutional review board approval, 63 direct MR arthrographic examinations of the hip in 61 patients with a clinical history of hip pain were retrospectively reviewed by two experienced musculoskeletal radiologists in consensus. The following variables were measured using a binary system (0 = absent; 1 = present): labral plica, neck plica, ligamental plica, labral tear, femoroacetabular impingement, and osteoarthritis. The surgical reports and arthroscopic images of 10 patients were reviewed. Statistical analysis was performed using the Fisher's exact test. RESULTS: In all 63 cases at least one plica was visualized on MR-arthrographic images. Labral, neck, and ligamental plicae were found with a prevalence of 76, 97, and 78%, respectively. There was no statistically significant association between the presence of labral tears, femoroacetabular impingement, and osteoarthritis among patients with visible labral, neck, and ligamental plicae. The prevalence of labral tears, femoroacetabular impingement, and osteoarthritis in our patient population was 79, 28, and 28%, respectively. The presence of intra-articular plicae was the only MR-arthrographic finding in 5 of our 63 symptomatic cases. CONCLUSION: Visible labral, neck, and/or ligamental plicae are highly prevalent on MR-arthrographic images of the hip performed in the setting of hip pain. There was no statistically significant association between the presence of labral tears, femoroacetabular impingement, and osteoarthritis and visible labral, neck, and ligamental plicae.

[Beginnings, evolution and current situation of the Newborn Screening Programs in Spain.] / Inicio, evolución y situación actual de los Programas de Cribado Neonatal en España.

Newborn Screening Programs (NSP) in Spain were born in the city of Granada in 1968. Till the 1980s, they were developed around the so-called "National Plan for Preventing Subnormality", covering up to 30% of the Spanish newborns. From 1982, when the health system management was transferred to the different autonomous regions, the NSP began to expand, and the bases to transform them into an organized and multidisciplinary activity, integrated and coordinated from the National Health System were settled. Despite this expansion, it is not until the 1990s when their coverage reaches almost 100% newborns in Spain. NSP grew up asymmetrically across the different autonomous regions. In 2005 and 2006 the scientific societies SEQC (Spanish Society of Clinical Chemistry) and AECNE (Spanish Society of Newborn Screening), coordinated by the Health Promotion Area of the General Directorate of Public Health, gathered together the necessary information to elaborate a report on the NSP in Spain addressed to the Interterritorial Council of the National Health System. In July 2013, that Council approved the seven diseases that should be part of each region newborn screening panel, being the first step towards the NSP harmonization in Spain. Currently, the NSP include between 8 and 29 diseases in their panels, thus more still more efforts are needed in order to achieve a higher uniformity.

Los Programas de Cribado Neonatal (PCN) nacen en España en Granada en el año 1968. Posteriormente, y hasta los años 80, se fueron desarrollando en torno al llamado "Plan Nacional de Prevención de la Subnormalidad" con una cobertura cercana al 30% de los recién nacidos españoles. A partir de 1982, con el inicio de la gestión de la sanidad a las comunidades autónomas (CCAA), los PCN se expandieron y se comenzaron a sentar las bases para que éstos se convirtieran en una actividad organizada y multidisciplinar, integrados y coordinados desde el Sistema de Salud. A pesar de dicha expansión no es hasta el inicio de la década de los 90 cuando se consigue una cobertura próxima al 100% de los RN en España. Los PCN fueron creciendo de forma muy asimétrica en las diferentes CCAA y en los años 2005 y 2006 las Sociedades Científicas SEQC (Sociedad Española de Química Clínica) y AECNE (Asociación Española de Cribado Neonatal), con la coordinación del Área de Promoción de la Salud de la Dirección General de Salud Pública, recopilaron la información y elaboraron un informe, sobre los PCN en España para el Consejo Interterritorial del sistema Nacional de Salud (CISNS). En julio de 2013 este Consejo aprobó las siete enfermedades que debían formar parte del panel de detección de los PCN territoriales, primer paso hacia la armonización de estos programas. Actualmente, los PCN incluyen entre 8 y 29 enfermedades por lo que es necesario seguir trabajando para conseguir una mayor uniformidad.

Squamous cell carcinoma related with dental implants. A clinical cases report.

One third of all cases of head and neck carcinoma (CA) concern the oral mucosa. The use of dental implants (DI) for dental rehabilitation is widely extended. However, a few studies have reported some cases with neoplasic alterations, among the tissue surrounding implants. Our aim was to analyze possible alterations at the bone-implant interface in patients with oral squamous cell carcinoma (SCC), providing new evidence that could relate or discard a possible link between these factors. We used, for the first time, different techniques, including electron microscopy and histology, to analyze the implant ´s surface and the surrounding tissue from four clinical cases with neoplasic alterations surrounding DI. Histologically, ample inflammatory tissue was found in direct contact with the implant surface. Surface analysis of this tissue, revealed titanium percentages. According to our study, no oncological relation with deterioration of the implant surface was found, although DI were constantly related with peri-implantitis, a chronic trauma of the oral mucosa that could involve a neoplastic factor. Key words:Dental implants, carcinoma, peri-implantitis.

Guía de práctica clínica para el tratamiento de infecciones odontogénicas en el Seguro Social de Salud del Perú (EsSalud) / Clinical practice guidelines for the treatment of odontogenic infection of the Peruvian Health Social Security (EsSalud)

Introducción. El presente artículo resume las recomendaciones basadas en evidencias de la guía de práctica clínica (GPC) para el tratamiento de los pacientes con infecciones odontogénicas (absceso dentoalveolar, celulitis facial y absceso cervicofacial) en el Seguro Social de Salud del Perú (EsSalud). Objetivo. Brindar recomendaciones clínicas basadas en evidencia para el tratamiento de pacientes con infecciones odontogénicas en EsSalud. Métodos. Se conformó un grupo elaborador de la guía (GEG) que incluyó cirujanos dentistas, especialistas y metodólogos. El GEG formuló cuatro preguntas clínicas a ser respondidas en la presente GPC. Se realizó búsquedas sistemáticas de revisiones sistemáticas y cuando fue considerado pertinente­ estudios primarios en PubMed y CENTRAL durante el año 2019. Se seleccionó la evidencia para responder cada una de las preguntas clínicas planteadas. La certeza de la evidencia fue evaluada usando la metodología Grading of Recommendations Assessment, Development, and Evaluation (GRADE). En reuniones de trabajo periódicas, el GEG usó la metodología GRADE para revisar la evidencia y formular las recomendaciones, los puntos de buena práctica clínica y el flujo- grama de tratamiento. Finalmente, la GPC fue aprobada con Resolución N° 067­IET- SI-ESSALUD-2020. Resultados. La presente GPC abordó cuatro preguntas clínicas, divididas en dos temas: manejo farmacológico y manejo quirúrgico de las infecciones odontogénicas. En base a dichas preguntas se formularon seis recomendaciones fuertes, dos recomendaciones condicionales, 11 puntos de buena práctica clínica, y un flujograma. Conclusión. El presente artículo resume la metodología y las conclusiones basadas en evidencias de la GPC para tratamiento de las infecciones odontogénicas (absceso dentoalveolar, celulitis facial y absceso cervicofacial) en EsSalud.

Introduction. This article summarizes the evidence-based recommendations of the clinical practice guide (CPG) for the treatment of patients with odontogenic infections (dentoalveolar abscess, facial cellulitis and cervicofacial abscess) in the Social Security of Health of Peru (EsSalud). Objective. To provide evidence-based clinical recommendations for the treatment of patients with odontogenic infections in EsSalud. Methods. A guideline development group (GEG) was formed that included dental surgeons, specialists, and methodologists. The GEG formulated four clinical questions to be answered in this CPG. We conducted systematic searches for systematic reviews and when deemed relevant - primary studies in PubMed and CENTRAL during 2019. The evidence was selected to answer each of the clinical questions posed. The certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the GEG used the GRADE methodology to review the evidence and formulate the recommendations, the points of good clinical practice and the treatment flow chart. Finally, the CPG was approved with Resolution No. 067 ­ IETSI-ESSALUD-2020. Results. This CPG addressed four clinical questions, divided into two topics: pharmacological management and surgical management of odontogenic infections. Based on these questions, six strong recommen- dations were formulated, two conditional recommendations, 11 points of good clinical practice, and a flow chart. Conclusion. This article summarizes the methodology and evidence-based conclusions of the CPG for the treatment of odontogenic infections (dentoalveolar abscess, facial cellulitis and cervicofacial abscess) in EsSalud.

Long-term effects of highly active antiretroviral therapy in pretreated, vertically HIV type 1-infected children: 6 years of follow-up.

BACKGROUND: Several studies of children with human immunodeficiency virus (HIV) type 1 infection have demonstrated sustained increases in CD4+ cell count, even when virological failure has occurred after receipt of highly active antiretroviral therapy (HAART), but these studies were of limited duration. Moreover, the CD4+ cell count threshold at which antiretroviral treatment should be initiated is still unsettled. The aim of this study was to define the long-term impact of HAART on CD4+ cell percentage and viral load according to CD4+ cell percentages before HAART was initiated. METHODS: We conducted a retrospective study of 113 pretreated HIV-1-infected children stratified by pre-HAART CD4+ cell percentage (<5%, 5%-15%, 15%-25%, and >25%). The inclusion criteria were as follows: initiating HAART with a protease inhibitor, having 6 years of follow-up after starting HAART, having a CD4+ cell count or viral load recorded before initiation of HAART, and having received mono- or dual-nucleoside therapy before starting HAART. RESULTS: During the first 2 years of HAART, HIV-1-infected children experienced a significant increase in CD4+ cell percentage and a decrease in viral load (P<.05). During their last 4 years of receiving HAART, we found a significant decrease in viral load but not an increase in CD4+ cell percentage, because the CD4+ cell percentage reached a plateau after the second year of HAART. Moreover, children with CD4+ cell percentages of <5% at baseline did not achieve CD4+ cell percentages of >25% after 6 years of HAART. Children with CD4+ cell percentages of 5%-25% at baseline had a strong negative association with achieving CD4+ cell percentages of >30% for at least 6 and 12 months but not with achieving CD4+ cell percentages of >30% for at least 24 months. CONCLUSIONS: Long-term HAART allowed for restoration of CD4+ cell counts and control of viral loads in HIV-1-infected children. However, initiating HAART after severe immunosuppression has occurred is detrimental for the restoration of the CD4+ cell count.

Hamstring injuries of the hip.

Hamstring injuries can be classified with regard to the site of involvement. Traumatic disorders at the proximal bone-tendon origin are best defined as avulsion injuries, such as ischial tuberosity fractures and hamstring tendon tears. Musculotendinous lesions include muscle strains and muscle contusions. Most hamstring injuries occur after in-direct trauma from excessive stretching or forceful contraction, leading to avulsion injuries or muscle strains and tears. Insufficient warm-up, lack of flexibility, inadequate muscle strength and endurance, or abnormal contraction and running may predispose to such injuries. In the event of blunt direct trauma, a muscle contusion, intramuscular hematoma, myositis ossificans, or compartment syndrome may develop.

Morel-Lavallée lesion: review with emphasis on MR imaging.

MR imaging is the diagnostic imaging modality of choice in the assessment of ML lesions in the hip region. Given their typical location, morphology, signal behavior, and enhancement pattern,ML lesions can be identified readily on MR examinations of the hip and proximal thigh.Correct preoperative MR diagnosis of ML lesions can be useful for treatment planning.

Estimating UV erythemal irradiance by means of neural networks.

In recent years, there has been a substantial increase in attempts to model the flux of ultraviolet radiation (UV). UV irradiance at surface level is a result of the combined effects of solar zenith angle, surface elevation, cloud cover, aerosol load and optical properties, surface albedo and the vertical profile of ozone. In this study, we present the development of an artificial neural network (ANN) model that can be used to estimate solar UV irradiance on the basis of optical air mass, ozone columnar content, latitude, horizontal visibility data and cloud information such as type, coverage and height. ANN are widely accepted as a technology offering an alternative way to tackle complex and ill-defined problems. They can learn from examples, are fault tolerant in the sense that they are able to handle noisy and incomplete data, are able to deal with nonlinear problems and, once trained, can perform prediction and generalization at high speed. In this study, a multilayer perceptron network (MLP) consisting of an input layer, an output layer and one hidden layer was used. Training of the neural network was done using the Bayesian regulation back propagation algorithm. The study was developed using data from three stations on the Iberian Peninsula: Madrid and Murcia during the period 2000-2001 and Zaragoza in 2001. To train and validate the MPL neural networks, independent subsets of data were extracted from the complete database at each station. The results suggest that a MLP neural network using optical air mass, ozone columnar content, latitude and total cloud coverage provides the best estimates, with mean bias deviation and root mean square deviation of -0.1% and 18.0%, 1.6% and 19.6%, 0.1% and 14.6% at Madrid, Murcia and Zaragoza, respectively. Despite the dependence of the cloud radiative effect on cloud type, the use of additional information such as cloud type or cloud elevation did not improve these results. The performance of the developed ANN has been checked regarding its ability to estimate the UV index (UVI); results indicate that in more than 95% of the cases, the difference between estimated and measured values does not exceed one unit of UVI.

The clinical relevance of microbiologic testing. Part 2: a comparative analysis of microbiologic samples secured simultaneously from the same sites and cultured in the same laboratory.

A field study using four different private periodontal practices and two independent laboratories was conducted to compare two microbiologic cultures sampled simultaneously from the same sites in 20 individual patients. Both paired samples were submitted separately to one of the two independent laboratories for bacterial identification and antibiotic sensitivity testing. The results from the two samples were quite variable. In only two instances did both specimens reveal the presence of identical bacterial species, but these specimens differed in both threshold levels and antibiotic sensitivity. When only bacteria above threshold levels were compared, total agreement was found in 11 of 20 cases. When examining antibiotic sensitivity, using 100% kill as the ideal, agreement between the two specimens was inconsistent The use or nonuse of tetracycline was in agreement 85% of the time, amoxicillin 75% of the time, metronidazole 70% of the time, and amoxicillin-metronidazole in combination 85% of the time. The two specimens agreed on the empirical use of amoxicillin 45% of the time, tetracycline 60% of the time, and metronidazole 60% of the time. The empirical use of amoxicillin-metronidazole in combination yielded 80% agreement when the results of both specimens were combined. The empirical use of amoxicillin-metronidazole combination therapy may be more clinically sound and cost effective than culturing and antibiotic selection based on the culture from any single microbiologic testing laboratory. This supports the data from a previous study that examined specimens secured simultaneously from the same site and submitted to two different testing laboratories. The failure of microbial testing to achieve a higher level of consistency between samples leaves the clinical efficacy of microbial testing in question.

Determination of antioxidant activity of spices and their active principles by differential pulse voltammetry.

The anodic oxidation of mercury in the presence of hydrogen peroxide in differential pulse voltammetry (DPV) was used to determine the antioxidant (AO) character of radical scavengers. Hydroperoxide radical is formed at the potentials of the oxidation peak on mercury electrodes, such radical reacting with the antioxidants in different extension. The parameter C10 (antioxidant concentration at which the peak area decreases by 10%) is used to measure the scavenging activity of the individual antioxidants. To establish the scavenging activity of antioxidant mixtures as a whole, the parameter, µ10 as the reverse of V10, V10 being the volume necessary to decrease the peak area in DPV by 10%, was selected. Higher µ10 values correspond to higher scavenging activity. The studies have been extended to aqueous extracts of some species. The results may be useful in explaining the effect of spices in vitro and in vivo studies.