Cervicofacial surgery and implantable hearing device extrusion: management of challenging cases.

OBJECTIVE: To describe our management of implantable hearing device extrusion in cases of previous cervicofacial surgery. METHODS: A review was conducted of a retrospectively acquired database of surgical procedures for implantable hearing devices performed at our department between January 2011 and December 2019. Cases of device extrusion and previous cervicofacial surgery are included. Medical and surgical management is discussed. RESULTS: Four cases of implant extrusion following cervicofacial surgery were identified: one involving a Bonebridge system and three involving cochlear implants. In all cases, antibiotic treatment was administered and surgical debridement performed. The same Bonebridge system was implanted in the middle fossa. The three cochlear implants were removed, and new devices were implanted in a more posterior region. CONCLUSION: Previous cervicofacial surgery is a risk factor for hearing implant extrusion. The middle fossa approach is the best option for the Bonebridge system. Regarding the cochlear implant, it is always suitable to place it in a more posterior area. An inferiorly based fascio-muscular flap may be a good option to reduce the risk of extrusion.

Pseudo mastoid obliteration with conchal cartilage may be a safe alternative technique for cochlear implantation in canal wall down mastoidectomy with large meatoplasty.

OBJECTIVE: Safe cochlear implantation is challenging in patients with canal wall down mastoid cavities, and the presence of large meatoplasties increases the risk of external canal overclosure. This paper describes our results of obliteration of the mastoid cavity with conchal cartilage as an alternative procedure in cases of canal wall down mastoidectomy with very large meatoplasty. METHODS: The cases of seven patients with a canal wall down mastoidectomy cavity who underwent cochlear implantation were retrospectively reviewed. Post-operative complications were analysed. The mean follow-up duration was 4.5 years. RESULTS: There was no hint of cholesteatoma recurrence and all patients have been free of symptoms during follow up. Only one patient showed cable extrusion six months after surgery, and implantation of the contralateral ear was needed. CONCLUSION: Pseudo-obliteration of the mastoid cavity with a cartilage multi-layered palisade reconstruction covering the electrode may be a safe alternative in selected patients with a large meatoplasty.

Endoscopic reconstruction of large anterior skull base defects with opening of the sellar diaphragm. Experience at a tertiary level university hospital.

BACKGROUND: The indications for expanded endoscopic transnasal approaches continue to increase, with more complex skull base defects needing to be repaired. This study reviews the management of large anterior skull base defects with opening of the sellar diaphragm. METHOD: A prospective analysis of endonasal endoscopic surgery carried out at Son Espases University Hospital between January 2013 and December 2018 was performed. The analysis included only the cases with a significative intra-operative cerebrospinal fluid leak. In all cases, reconstruction was performed by combining the gasket seal technique with a pedicled mucosal endonasal flap. RESULTS: Twenty-eight patients were included. The mucoperiosteal nasoseptal flap, the lateral wall flap and the middle turbinate flap were used in 13, 8 and 7 patients, respectively, combined with the gasket seal technique. One case of post-operative cerebrospinal fluid leak was observed (3.57 per cent). CONCLUSION: The combination of a gasket seal with an endonasal mucosal flap is an excellent technique for repairing large anterior skull base defects.

Tissue chips - innovative tools for drug development and disease modeling.

The high rate of failure during drug development is well-known, however recent advances in tissue engineering and microfabrication have contributed to the development of microphysiological systems (MPS), or 'organs-on-chips' that recapitulate the function of human organs. These 'tissue chips' could be utilized for drug screening and safety testing to potentially transform the early stages of the drug development process. They can also be used to model disease states, providing new tools for the understanding of disease mechanisms and pathologies, and assessing effectiveness of new therapies. In the future, they could be used to test new treatments and therapeutics in populations - via clinical trials-on-chips - and individuals, paving the way for precision medicine. Here we will discuss the wide-ranging and promising future of tissue chips, as well as challenges facing their development.

Research challenges in central nervous system manifestations of inborn errors of metabolism.

The Research Challenges in CNS Manifestations of Inborn Errors of Metabolism workshop was designed to address challenges in translating potential therapies for these rare disorders, and to highlight novel therapeutic strategies and innovative approaches to CNS delivery, assessment of effects and directions for the future in the treatment of these diseases. Therapies for the brain in inborn errors represent some of the greatest challenges to translational research due to the special properties of the brain, and of inborn errors themselves. This review covers the proceedings of this workshop as submitted by participants. Scientific, ethical and regulatory issues are discussed, along with ways to measure outcomes and the conduct of clinical trials. Participants included regulatory and funding agencies, clinicians, scientists, industry and advocacy groups.

Actualización en el tratamiento médico del carcinoma renal avanzado / Update on the medical treatment of advanced kidney cancer

El tratamiento quirúrgico del cáncer de células renales (CCR) avanzado se ve reforzado por la aplicación de fármacos con capacidad citorreductora. La inmunodependencia del CCR lo hace sensible a terapias como la Interleukina e el Interferón, aunque los resultados son discretos. Nuevas terapias médicas han conseguido mejores resultados. Dentro del grupo de los inhibidores de las multiquinasas, el Sunitinib bloquea los receptores del VEGF, PDGFR, C-Kit, FLT-3 tirosina quinasa que juegan un papel en la carcinogénesis del CCR; y el Sarafenib bloquea VEGFR-2 y PDGFR por inhibición de RAF-1. Por su parte de anticuerpos anti-VEGF, como el Bavicizumab neutralizan la actividad de VEGF-A. Los inhibidores de mTOR, como el Tensirolimus, y el Everolimus, inhiben a la rapamicina-quinasa, responsable de la proliferación y la hipoxia celular. Se presenta un caso de CCR avanzado con buena respuesta al tratamiento médico (AU)

Surgical treatment of renal cell cancer (RCC) is reinforced by the application of drugs with cytoreductive capacity. The CRC inmunomodulation makes it amenable to therapies such as interleukin and interferon, although the results are discrete. New medical therapies have better results. Within the group of the multi-kinase inhibitors, Sunitinib blocks the receptors of VEGF, PDGFR, C-kit and FLT-3 tyrosine kinase that plays a role in carcinogenesis soft RCC, while Sorafenib blocks VEGFR-2 and PDGFR through inhibition RAF—1. Anti-VEGF antibodies such as Bevacizumab neutralize the activity of VEGF-A. MTOR inhibitors, such as Tensirolimus and Everolimus, inhibits rapamycin-kinase responsible for proliferation and cellular hypoxy. A case of advanced RCC with good response to treatment is presented (AU)

Botox, mucho más que arrugas / Botox, much more tan rides

El primer tratamiento para los pacientes con vejiga inestable son los fármacos anticolinérgicos, que, sin embargo, pueden ser inefectivos o producir efectos adversos. Se han buscado otros tipos de tratamiento como son la neuromodulación o el tratamiento intravesical con toxina botulínica (Botox). Existe una evidencia creciente acerca de la utilidad de la inyección de toxina botulínica en el detrusor para el tratamiento de la hiperactividad vesical. Existen diferentes indicaciones en urología para el Botox aunque no están aceptadas oficialmente: el detrusor hiperactivo neurógeno e idiopático, la disinergia vésico-esfíteriana, cistopatía intersticial y dolor prostático crónico. Presentaremos dos casos clínicos para revisar las diferentes aplicaciones de Botox en urología (AU)

The first treatment for patients with unstable bladder are anticholinergics drugs, however, may be ineffective or cause side effects. Has been sought other types of treatment such as neuromodulation or intravesical treatment with Botulinic Toxine (Botox). There is growing evidence of the usefulness of botulinum toxin injection into the detrusor for the treatment of overactive bladder. There are different indications for Botox in urology but are not officially accepted: neurogenic and idiopathic overactive detrusor, the detrusor-sphincter, interstitial cystitis and chronic prostatic pain. We present two cases to review the various applications of Botox in urology (AU)

Nefrocalcinosis: conceptos básicos, etiología y tratamiento médico. Revisión desde un enfoque urológico / Nefrocalcinosis: basic concepts, etiology and medical treatment. Review from an urological focus

Presentamos el caso de un paciente varón de 46 años de edad, quien inició su historia litiásica a los 26 años con cólicos nefríticos expulsivos, tratados habitualmente con analgésicos comunes y antiinflamatorios. El estudio cristalográfico reveló cristales de oxalato de calcio dihidratado y fosfato de calcio apatílico. La urografía intravenosa demostró la presencia de calcificaciones medulares bilaterales múltiples, con funcionalismo conservado y ausencia de uropatía obstructiva. Se asumió el caso como nefrocalcionsis medular bilateral, probablemente secundaria a hipercalciuria y/o acidosis tubular distal tipo I. El paciente ha sido medicado con citrato potásico hasta la actualidad. Se exponen a continuación las siguientes causas de nefrocalcinosis, haciendo mención especial de las principales: Hiperparatiroidismo primario; Hipercalciuria idiopática; Acidosis tubular distal tipo I y Enfermedad de Cacchi-Ricci (enpongiosis Medular Renal) (AU)

We present the case of a 46 year old male patient, who initiated his lithiasic history at the age of 26 with expulsive renal colic’s, usually treated with common analgesics and anti-inflammatory. The crystallographic study revealed calcium oxalate dihydratte and calcium phosphate apatite crystals. The Intravenous Pyelogram showed the presence of multiple bilateral medullary calcifications, with preserved functionalism and absence of obstructive uropathy. The case was assumed as bilateral nephoraclcinosis, due probably to hypercalciuria and (or distal renal tubular acidosis (type 1). The patient has been medicated with potassium citrate until the present time. The following causes of nefrocalcinosis are exposed next, doing special mention of the main ones: Primary Hiperparatiroidism; Idiopatic Hipercalciuria; Distal Renal tubular Acidosis (type I) and Cacchi-Ricci (Medullary Sponge Kidney) disease

Crioterapia como tratamiento del cancer renal / Cryotherapy as a treatment for kidney cáncer

El diagnóstico precoz de pequeñas masas renales ha aumentado gracias a la masiva utilización de técnicas de imagen como ecografía, TAC y RMN. Frente a estas lesiones, muchas de ellas incidentales, se plantean diversas posibilidades de tratamiento, teniendo cada vez más tendencia a la realización de técnicas conservadoras como la nefrectomía parcial laparoscópica y técnicas ablativas con crioterapia o radiofrecuencia. Presentamos un caso de mas renal de pequeño tamaño tratada con crioterapia, revisando algunos aspectos técnicos de su realización (AU)

Early diagnosis of small renal masses has increased thanks to the massive use of imaging techniques like ultrasound, CT and MRI. To treat these masses, many of which are incidental, there are various treatment options, taking increasing trend towards conducting conservative techniques such as laparoscopic partial nephrectomy and ablative techniques with cryotherapy or radiofrequency. We report a case of a small renal mass treated with cryotherapy, reviewing some technical aspects of your implementation (AU)

Fístula arteriovenosa renal. A propósito de un caso rebelde a la embolización / Arterryo-venous fistula. A clinical case refractary to embolization

Las fístulas arteriovenosas (FAV) renales son infrequentes aunque actualmente la incidencia de las fístulas adquiridas está en incremento debido al aumento de los procesos percutáneos, tales como la nefrostomía y la biopsia renal. Presentamos el caso de una mujer de 37 años que a raíz de un dolor inespecífico lumbar se realizó una ecografía y una RMN diagnosticándose una FAV. Se realizaron dos embolizaciones de la fístula consiguiendo disminuir su tamaño, presentando posteriormente HTZ. Se realizó como tratamiento definitivo una nefrectomía radical. A propósito de este caso se realiza una breve revisión de la literatura

Arteriovenous fistula (AVF) is uncommonn, however the increase of percutaneous renal procedures nowadays, as the renal biopsy as the nephrostomy, have rising the incidence of this pathological condition. We report a case of 37 years old woman with a FAV diagnosed by echography and MR, after unspecific flank pain episode. The treatment was two emblectomies with arterial flow reduction but without AVF extinction. The patient shoed hypertensive crisis and a definitive treatment with total nephrectomy was performed. We make a brief review of the literature about renal AVF

Cateterización ureteral anterógrada: una indicación actual / Antegrade ureteral catheterization: a present indication

Existen situaciones de obstrucción del tracto urinario superior, en las cuales no es posible la cateterización ureteral en forma retrógrada (forma clásica) y se hace necesario realizar una nefrostomía. La instalación de un catéter pigtail en forma anterógrada, utilizando la vía percutánea, logra un adecuado drenaje de la vía urinaria, evitando así la necesidad de una nefrostomía. En este trabajo exponemos nuestra experienciaal instalar 10 catéteres ureterales tipo pigtail en 6 pacientes, vía percutánea y describiendo la técnica utilizada. Concluimos que esta técnica logra un adecuado drenaje de la vía urinaria, es segura y da una mejor calidad de vida, la que puede ser realizada en forma ambulatoria.

Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease.

Neurons in Huntington's disease exhibit selective morphological and subcellular alterations in the striatum and cortex. The link between these neuronal changes and behavioral abnormalities is unclear. We investigated relationships between essential neuronal changes that predict motor impairment and possible involvement of the corticostriatal pathway in developing behavioral phenotypes. We therefore generated heterozygote mice expressing the N-terminal one-third of huntingtin with normal (CT18) or expanded (HD46, HD100) glutamine repeats. The HD mice exhibited motor deficits between 3 and 10 months. The age of onset depended on an expanded polyglutamine length; phenotype severity correlated with increasing age. Neuronal changes in the striatum (nuclear inclusions) preceded the onset of phenotype, whereas cortical changes, especially the accumulation of huntingtin in the nucleus and cytoplasm and the appearance of dysmorphic dendrites, predicted the onset and severity of behavioral deficits. Striatal neurons in the HD mice displayed altered responses to cortical stimulation and to activation by the excitotoxic agent NMDA. Application of NMDA increased intracellular Ca(2+) levels in HD100 neurons compared with wild-type neurons. Results suggest that motor deficits in Huntington's disease arise from cumulative morphological and physiological changes in neurons that impair corticostriatal circuitry.

A novel isoform of beta-spectrin II localizes to cerebellar Purkinje-cell bodies and interacts with neurofibromatosis type 2 gene product schwannomin.

We report the identification of a full-length novel beta-spectrin II gene (betaSpIIsigma2) in human brain. The betaSpIIsigma2 gene has 32 exons encoding an actin-binding domain, followed by 17-spectrin repeats, and a short COOH-terminal regulatory region that lacks the Pleckstrin homology (PH) domain. Pair-wise sequence analysis showed an additional 36 and 28 amino acids located at the NH2 and COOH-terminal regions of betaSpIIsigma2, respectively. Northern-blot analysis showed an abundant expression of betaSpIIsigma2 transcripts in brain, lung, and kidney. Western-blot analysis confirmed the predicted approximately 225 kD molecular size of betaSpIIsigma2 protein in these same tissues. In brain, immunofluorescent staining revealed that betaSpIIsigma2 was enriched in cerebellar neurons, with specific enrichment in Purkinje cell bodies, but not in dendrites. Of considerable interest, neurofibromatosis type 2 (NF2) gene product schwannomin was found to co-immunoprecipitate with betaSpIIsigma2 in cultured Purkinje cells. These results suggest that betaSpIIsigma2 may play an important role in the assembly of the specialized plasma membrane domain of Purkinje neurons and that schwannomin may be involved in actin-cytoskeleton organization by interacting with betaSpIIsigma2.

Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production.

Mitochondrial defects, which occur in the brain of late-stage Huntington's disease (HD) patients, have been proposed to underlie the selective neuronal loss in the disease. To shed light on the possible role of mitochondrial energy impairment in the early phases of HD pathophysiology, we carried out Golgi impregnation and quantitative histochemical/biochemical studies in HD full-length cDNA transgenic mice that were symptomatic but had not developed to a stage in which neuronal loss could be documented. Golgi staining showed morphologic abnormalities that included a significant decrease in the number of dendritic spines and a thickening of proximal dendrites in striatal and cortical neurons. In contrast, measurements of mitochondrial electron transport Complexes I-IV did not reveal changes in the striatum and cerebral cortex in these mice. Examination of the neostriatum and cerebral cortex in human presymptomatic and pathological Grade 1 HD cases also showed no change in the activity of mitochondrial Complexes I-IV. These data suggest that dendritic alterations precede irreversible cell loss in HD, and that mitochondrial energy impairment is a consequence, rather than a cause, of early neuropathological changes.

A de novo complex chromosomal rearrangement with a translocation 7;9 and 8q insertion in a male carrier with no infertility.

A de novo complex chromosomal rearrangement (CCR) involving chromosomes 7, 8 and 9 in a male carrier was ascertained through his healthy wife's recurrent spontaneous abortions. Six pregnancies over eight years resulted in four spontaneous abortions and two livebirths who died perinatally due to abnormal vital signs. Cytogenetic analyses utilizing high resolution chromosome banding technique showed a deletion of band in a der(7) chromosome and an extra band inserting at 8q21.2. Another extra band was also observed at the band 9p24, but it could not be karyotypically determined. Fluorescent in-situ hybridization using chromosome 7 and 8 specific microdissected library as probes confirmed the insertion of a segment from the translocated chromosome 7 into a chromosome 8, and additionally revealed a translocation between chromosomes 7 and 9. The karyotype of the CCR carrier was determined as 46,XY,t(7;9)(q22;p24),ins(8;7)(q21.2;q22q32).ish der(9)(wcp7+);ins(8;7)(wcp8+,wcp7+). Comparing with previously reported male CCR carriers with our case, we conclude that male CCR carriers may not always present with infertility or subfertility phenotypes. This may suggest that rare transmission of male carriers could result from abnormal chromosomal rearrangements during meiosis and gametogenesis in addition to frequent infertility.

Alpha-synuclein immunoreactivity of huntingtin polyglutamine aggregates in striatum and cortex of Huntington's disease patients and transgenic mouse models.

Polyglutamine expansions in proteins are implicated in at least eight inherited neurodegenerative disorders, including Huntington's disease. These mutant proteins can form aggregates within the nucleus and processes of neurons possibly due to misfolding of the proteins. Polyglutamine aggregates are ubiquitinated and sequester molecular chaperone proteins and proteasome components. To investigate other protein components of polyglutamine aggregates, cerebral cortex and striata from patients with Huntington's disease and full-length cDNA transgenic mouse models for this disease were examined immunohistochemically for alpha-synuclein reactivity. Our findings demonstrate that alpha-synuclein can be used as a marker for huntingtin polyglutamine aggregates in both human and mice. Moreover in the HD transgenic mice, the intensity of immunoreactivity increases with age. The significance of recruitment of alpha-synuclein into huntingtin aggregates and its translocation away from the synapses remains to be determined. We propose that aberrant interaction of mutant huntingtin with other proteins, including alpha-synuclein, may influence disease progression.