Epigenomic and transcriptomic landscaping unraveled candidate repositioned therapeutics for non-functioning pituitary neuroendocrine tumors.

PURPOSE: Non-functioning pituitary neuroendocrine tumors are challengingly diagnosed tumors in the clinic. Transsphenoidal surgery remains the first-line treatment. Despite the development of state-of-the-art techniques, no drug therapy is currently approved for the treatment. There are also no randomized controlled trials comparing therapeutic strategies or drug therapy for the management after surgery. Therefore, novel therapeutic interventions for the therapeutically challenging NF-PitNETs are urgently needed. METHODS: We integrated epigenome and transcriptome data (both coding and non-coding) that elucidate disease-specific signatures, in addition to biological and pharmacological data, to utilize rational pathway and drug prioritization in NF-PitNETs. We constructed an epigenome- and transcriptome-based PPI network and proposed hub genes. The signature-based drug repositioning based on the integration of multi-omics data was performed. RESULTS: The construction of a disease-specific network based on three different biological levels revealed DCC, DLG5, ETS2, FOXO1, HBP1, HMGA2, PCGF3, PSME4, RBPMS, RREB1, SMAD1, SOCS1, SOX2, YAP1, ZFHX3 as hub proteins. Signature-based drug repositioning using hub proteins yielded repositioned drug candidates that were confirmed in silico via molecular docking. As a result of molecular docking simulations, palbociclib, linifanib, trametinib, eplerenone, niguldipine, and zuclopenthixol showed higher binding affinities with hub genes compared to their inhibitors and were proposed as potential repositioned therapeutics for the management of NF-PitNETs. CONCLUSION: The proposed systems' biomedicine-oriented multi-omics data integration for drug repurposing to provide promising results for the construction of effective clinical therapeutics. To the best of our knowledge, this is the first study reporting epigenome- and transcriptome-based drug repositioning for NF-PitNETs using in silico confirmations.

Diagnosis of central nervous system infection by CSF sampling of the myelomeningocele sac as an alternative to ventricular tap.

BACKGROUND: Infection significantly affects mortality and morbidity in myelomeningocele cases. Ventricular tap is the most common method performed to diagnose central nervous system (CNS) infection in myelomeningocele patients. However, the ventricular tap can cause serious trauma to the baby and to the family. Here we discuss the technique of taking a cerebrospinal fluid (CSF) sample from the sac in myelomeningocele cases. METHODS: The study comprised 24 myelomeningocele patients undergoing sac repair; 7 patients in the early period and 17 in the late period (after the first 24 hours). CSF samples were taken from the sac and via ventricular tap. In all patients' samples, cell count and cultures were compared. RESULTS: In patients who underwent early meningomyelocele repair there was no significant difference between sac and ventricular CSF. There were also no positive cultures in samples taken from both areas. In comparison, in the group submitted to late repair, the number of cells in the sac and ventricle CSF samples was over 10 in 4 of the 17 patients. The cultures from CSF samples taken from both areas were positive for E. coli. In 13 of 17 patients who were admitted to our clinic for late repair, there was no significant difference between the number of cells in the sac and in ventricular samples. Cultures taken from these patients were negative. CONCLUSION: Puncture of the sac represents a quicker and more convenient way to obtain CSF in myelomeningocele cases. In addition, there was no increase in pain to a level that would cause stress for the baby. A CSF sample can be taken from the sac for diagnosis of CNS infection in myelomeningocele patients. This method, therefore, represents a safer and more comfortable option for both the patient and doctor.

Diagnosis of central nervous system infection by CSF sampling of the myelomeningocelesac as an alternative to ventricular tap

Background. Infection significantly affects mortalityand morbidity in myelomeningocele cases. Ventriculartap is the most common method performed to diagnosecentral nervous system (CNS) infection in myelomeningocelepatients. However, the ventricular tap can causeserious trauma to the baby and to the family. Here wediscuss the technique of taking a cerebrospinal fluid(CSF) sample from the sac in myelomeningocele cases.Methods. The study comprised 24 myelomeningocelepatients undergoing sac repair; 7 patients in theearly period and 17 in the late period (after the first 24hours). CSF samples were taken from the sac and viaventricular tap. In all patients’ samples, cell count andcultures were compared.Results. In patients who underwent early meningomyelocelerepair there was no significant differencebetween sac and ventricular CSF. There were also nopositive cultures in samples taken from both areas. Incomparison, in the group submitted to late repair, thenumber of cells in the sac and ventricle CSF sampleswas over 10 in 4 of the 17 patients. The cultures fromCSF samples taken from both areas were positive for E.coli. In 13 of 17 patients who were admitted to our clinicfor late repair, there was no significant difference betweenthe number of cells in the sac and in ventricularsamples. Cultures taken from these patients were negative.Conclusion. Puncture of the sac represents a quickerand more convenient way to obtain CSF in myelomeningocelecases. In addition, there was no increase inpain to a level that would cause stress for the baby. ACSF sample can be taken from the sac for diagnosisof CNS infection in myelomeningocele patients. Thismethod, therefore, represents a safer and more comfortableoption for both the patient and doctor (AU)

Fundamentos. La infección de LCR afecta significativamentela mortalidad y morbilidad en pacientes conmielomeningocele. La punción ventricular es la técnicamás frecuentemente utilizada para detectar infección delSNC en los casos de mielomeningocele. Sin embargo, lapunción ventricular puede causar un grave estrés tantopara el niño como para la familia. En nuestro estudio,presentamos la técnica y resultados del examen de LCRobtenido a partir del saco del mielomeningocele.Pacientes y métodos. El estudio comprende 24 pacientescon mielomeningocele sometidos a cierre quirúrgicode la malformación, 7 pacientes con reparaciónprecoz y 17 con cirugía tardía (después de las primeras24 horas). Las muestras de LCR fueron obtenidas delsaco de la malformación y de los ventrículos mediantepunción ventricular. Se compararon los resultados delrecuento de células y los cultivos realizados a todos lospacientes.Resultados. En los pacientes operados precozmente,no se encontraron diferencias significativas entre elLCR lumbar y ventricular. Tampoco se obtuvieroncultivos positivos en las muestras tomadas de ambasáreas. En los operados después de las primeras 24horas, el recuento de células del LCR del saco y delventrículo fue alrededor de 10 en 4 de los 17 pacientes.Se obtuvieron cultivos positivos (E. coli) de las muestrasde LCR tomadas de ambas áreas. En 13 de 17 pacientesque fueron admitidos a nuestra clínica para reparacióntardía, no hubo una diferencia significativa entre elnúmero de células del saco y del LCR ventricular. Loscultivos de LCR obtenidos en estos pacientes fueron (..) (AU)

Gamma-knife radiosurgery in the treatment of trigeminal schwannomas.

BACKGROUND: Trigeminal nerve schwannomas account for 0.07%-0.28% of all intracranial tumours. Advances in skull base surgery have led to more aggressive resection of these tumours, but surgery may associated with development of new neurological deficits. METHODS: In this report, we analyse the long-term results 15 patients with newly diagnosed or residual/recurrent trigeminal schwannoma who underwent gamma-knife treatment. FINDINGS: During a mean 61 months of follow-up, MRI revealed reduction of tumour size in 13 and no size change in 2 patients. The tumour growth control rate was 100% and only 1 patient had transient facial numbness and diplopia. CONCLUSIONS: For patients with small to moderate size trigeminal schwannomas, gamma-knife radiosurgery is associated with good tumour control and a minimal risk of adverse radiation effects.