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.

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.

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.

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.

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.

Uncommon causes of acute abdominal pain: multidetector computed tomography pearls and pitfalls for the radiologist on call.

We review uncommon causes of acute abdominal pain in which inconclusive multidetector computed tomography (MDCT) studies were followed by emergency surgery and unexpected diagnoses. Despite dedicated protocols and technical advances, MDCT of uncommon causes of acute abdominal pain still represents a significant challenge for the radiologist on call. We emphasize diagnostic pearls and pitfalls that may help the radiologist on call identify or suspect these uncommon causes of acute abdominal pain on MDCT.

[Expanded newborn screening in the Region of Murcia, Spain. Three-years experience]. / Cribado neonatal ampliado en la Región de Murcia. Experiencia de tres años.

BACKGROUND AND OBJECTIVE: The early detection of inborn errors of metabolism by mass spectrometry allows expanding the traditional neonatal screening of phenylketonuria and congenital hypothyroidism to test for aminoacidopathies, fatty acid oxidation disorders and organic acid metabolic disorders. Cystic fibrosis and biotinidase deficiency screening is implemented in the Region of Murcia. The aim of the study is to describe our experience in the expanded neonatal screening and to define the prevalence of each of the metabolic disorders early detected. PATIENTS AND METHODS: Since March 2007 until October 2010, a total of 71,595 neonates were screened with this expanded program by mass spectrometry, fluoroimmunoassay or colorimetric methods. RESULTS: Thirty-eight patients (prevalence 1:1,884) were diagnosed of inborn errors of metabolism by mass spectrometry, 13 patients of cystic fibrosis (prevalence 1:5,507), 38 of congenital hypothyroidism (prevalence 1:1,884) and one of biotinidase deficiency. To date, the global frequency of inborn errors of metabolism is estimated to be 1:804. The positive predictive value for the results obtained by mass spectrometry was 20.25%. Two false negative patients were not identified (cystic fibrosis and methylmalonic aciduria patients) and 6 non neonatal patients were detected through expanded neonatal screening. CONCLUSIONS: Our data support the necessity of unifying the set of metabolic diseases to be screened in all Regions of Spain for early detection of a defined panel of inborn errors of metabolism and to provide every newborn the same opportunities to be early diagnosed.

Sarcoidosis as a diagnostic pitfall of pancreatic cancer.

Sarcoidosis (SA) is accompanied by malignancy more than can be explained by chance. Cancer can occur in patients with an established diagnosis of SA and SA can subsequently develop in a cancer patient. Malignancy can also be associated with the occurrence of sarcoid reactions (SR), which are typically restricted to the regional lymph nodes. Problems may also arise in distinguishing between tumour-related SRs and true systemic SA. Here we present a case with both SA and pancreatic cancer, and we discuss the result of distinguishing between SA and SRs in a patient with concurrent cancer.

Magnetic resonance imaging features of the discrete epiphyseal radiolucency: a problem-solving approach to differential diagnosis.

Discrete radiolucencies in the epiphysis of the long bones may be a major radiographic finding in many arthropathies and synovial-based processes, and also in various osteolytic tumors and tumor-like lesions. In addition, a number of miscellaneous bone disorders, particularly infection and avascular necrosis, may present as discrete epiphyseal radiolucencies. Magnetic resonance imaging is frequently used in the diagnostic workup of these lesions. Our purpose was to review and illustrate, in a problem-solving approach, the potential contributions of magnetic resonance imaging in the characterization of discrete epiphyseal radiolucent lesions.

Objective patellar instability: MR-based quantitative assessment of potentially associated anatomical features.

To evaluate and compare the diagnostic utility of multiple quantitative parameters as measured on knee magnetic resonance (MR) examinations of patients suffering objective patellar instability (OPI). We performed a retrospective evaluation of knee MR examinations in a group of 46 patients (59 knees) with clinically proven OPI, and in a control group of 69 patients (71 knees). Multiple quantitative parameters in both groups were statistically evaluated and compared for their association with OPI. OPI patients tend to present shallower trochlear groove (<5 mm), larger Insall-Salvati index (>1.2), shorter patellar nose (<9 mm), smaller morphology ratio (<1.2), and larger patellar tilt (>11 degrees ) than control patients. The best sensitivities were those of the lateral patellar tilt (92.7%), the trochlear groove depth at the roman arch level (85.7%) and the Insall-Salvati index (78%). The best specificities were those of the morphology ratio (86.9%), the patellar nose (84.5%) and the patellar tendon length (84.5%). Shallow trochlear groove may be confidently identified at the roman arch view in OPI patients. Patella alta may be more reliably detected by the Insall-Salvati index in OPI patients. Patellar nose and morphology ratio are very specific indicators of OPI. A short patellar nose (that is to say, a patellar nose ratio of <0.25) has a high association with OPI. Lateral patellar tilt remains the single feature with the highest sensitivity and specificity for identifying OPI patients.

MR imaging of spinal infection: atypical features, interpretive pitfalls and potential mimickers.

The wide variability of MR features in spinal infection reflects rare distribution of discovertebral involvement, unexpected soft-tissue and bone abnormalities, un-usual complications or uncommon pathogens. In addition, several de-generative and inflammatory entities can clinically and radiologically resemble spinal infection. In this pictorial review, we illustrate the various atypical features that may be found in MR imaging of spinal infection,with emphasis on interpretative pit-falls and common mimickers.