The genomic profiling of high-risk smoldering myeloma patients treated with an intensive strategy unveils potential markers of resistance and progression.

Smoldering multiple myeloma (SMM) precedes multiple myeloma (MM). The risk of progression of SMM patients is not uniform, thus different progression-risk models have been developed, although they are mainly based on clinical parameters. Recently, genomic predictors of progression have been defined for untreated SMM. However, the usefulness of such markers in the context of clinical trials evaluating upfront treatment in high-risk SMM (HR SMM) has not been explored yet, precluding the identification of baseline genomic alterations leading to drug resistance. For this reason, we carried out next-generation sequencing and fluorescent in-situ hybridization studies on 57 HR and ultra-high risk (UHR) SMM patients treated in the phase II GEM-CESAR clinical trial (NCT02415413). DIS3, FAM46C, and FGFR3 mutations, as well as t(4;14) and 1q alterations, were enriched in HR SMM. TRAF3 mutations were specifically associated with UHR SMM but identified cases with improved outcomes. Importantly, novel potential predictors of treatment resistance were identified: NRAS mutations and the co-occurrence of t(4;14) plus FGFR3 mutations were associated with an increased risk of biological progression. In conclusion, we have carried out for the first time a molecular characterization of HR SMM patients treated with an intensive regimen, identifying genomic predictors of poor outcomes in this setting.

[Situs inversus of the optic nerve. A case report]. / Situs inversus del nervio optico. A proposito de un caso.

INTRODUCTION: Situs inversus of the optic nerve is a congenital anomaly characterised by the emergence of the vessels in the retina towards the nose rather than in a temporal direction. It is caused by an anomalous insertion of the optic stalks into the optic vesicle that gives rise to dysversion of the head of the optic nerve. It is not an isolated condition and usually appears jointly with tilted disc syndrome and in patients with myopia. It is characterised by the presence of inferior conus atrophy, deficiencies in the temporal visual field, refraction defects and ambliopy. CASE REPORT: A 22 years-old female who attended an ophthalmological examination due to severe frontal headaches accompanied by halos and loss of sharpness in her sight. From the results of the ophthalmetric and ophthalmological examination she was diagnosed as suffering from a condition consistent with this congenital anatomical anomaly. CONCLUSIONS: Situs inversus of the optic nerve is a rare condition that may appear in isolation or accompanied by other pathologies. Application of the visual field test and new diagnostic techniques, such as optical coherence tomography, facilitates the differential diagnosis of this situation. Its prevalence remains unknown, as it is not included in the register of rare diseases. Moreover, the scant number of patients studied and the scarce literature on this anomaly do not allow us to know whether the defects it causes develop over time. It would therefore be important to perform an ophthalmological follow-up of patients with situs inversus of the optic nerve.

TITLE: Situs inversus del nervio optico. A proposito de un caso.Introduccion. El situs inversus del nervio optico es una anomalia congenita caracterizada por la emergencia de los vasos de la retina en direccion nasal en lugar de temporal. Es causado por una anomala insercion del tallo optico en la vesicula optica que da lugar a la variacion de disposicion de la cabeza del nervio optico. No es una condicion aislada y suele aparecer junto con el sindrome del disco inclinado y en pacientes con miopia. Se caracteriza por la presencia de un cono de atrofia inferior, defectos en el campo visual temporal, defectos de refraccion y ambliopia. Caso clinico. Mujer de 22 años, que acude a revision oftalmologica por presentar fuertes cefaleas frontales acompañadas de halos y perdida de nitidez en la vision. Tras un examen optometrico y oftalmologico se llega al juicio clinico de que padece un cuadro compatible con esta anomalia anatomica congenita. Conclusiones. El situs inversus del nervio optico es una condicion rara que puede aparecer aislada o acompañada de otras patologias. La aplicacion de la campimetria y de nuevas tecnicas diagnosticas, como la tomografia de coherencia optica, facilita el diagnostico diferencial de esta situacion. No se conoce su prevalencia, pues no se encuentra en el registro de las enfermedades raras. Ademas, el escaso numero de pacientes estudiados y la exigua bibliografia existente sobre esta anomalia no permiten conocer si los defectos causados progresan en el tiempo, por lo que seria importante realizar un seguimiento oftalmologico de los pacientes con situs inversus del nervio optico.

Helical CT without contrast in choledocholithiasis diagnosis.

The goal of this study was to determine the diagnostic value of the helical CT without contrast in suspected cases of choledocholithiasis, comparing this test with endoscopic retrograde cholangiopancreatography (ERCP). Forty patients with possible choledocholithiasis were studied prospectively. There were 23 women and 17 men, ranging in age from 24 to 91 years. Helical CT was performed immediately before ERCP (time interval between the two procedures was less than 1 h). A biliary area previously selected was studied with a technique of pitch 1 and slice thickness of 3.2 mm. Average time was 30 s. Reconstruction with different increments and windows were made. Stone presence was evaluated in bile duct and Vater's ampulla. Biliary dilation was evaluated too. Endoscopic retrograde cholangiopancreatography found stones in 19 patients and absence of stones in 20. One case was failed, but stones in bile duct were demonstrated during intraoperative cholangiography. Helical CT demonstrated stones in 15 of the 19 patients with positive ERCP. There were no false positives with CT. Patients without stones in ERCP were also negative in CT. The patient having the failed ERCP was considered positive in CT. The CT sensitivity was 80% and specificity was 100%, with an accuracy of 90%. Helical CT without contrast has sensitivity and specificity good enough to be used as a screening technique in patients with suspected choledocholithiasis.

[Psychopedagogic rehabilitation of learning disorders in school children]. / Intervención psicopedagógica en las dificultades del aprendizaje escolar.

In this paper we discuss the main contributions of the three theoretical perspectives of psychology--conductual, cognitive and socio-historical--of education when there are learning difficulties. Finally, we emphasize the inefficacy of interventions and the need for implication in both the cognitive and meta-cognitive problems, and the socio-effective and conductual problems of these students.