Osteogenic parameters surrounding trabecular tantalum metal implants in osteotomies prepared via osseodensification drilling.

BACKGROUND: Surgical fixation of implants into bone for the correction of bone deformities or defects is a traditional approach for skeletal stabilization. Important measures of efficacy of implants include implant stability and osseointegration-the direct interaction between living bone and an implant. Osseointegration depends on successful implant placement and subsequent bone remodeling. This study utilized osseodensification drilling (OD) in a low bone density model using trabecular metal (TM) implants. MATERIAL AND METHODS: Three osteotomy sites, Regular, OD-CW (clockwise), and OD-CCW (counterclockwise), were prepared in each ilium of three female sheep. Drilling was performed at 1100rpm with saline irrigation. Trabecular metal (TM) (Zimmer, Parsippany, NJ, USA) implants measuring 3.7mm in diameter x 10mm length were placed into respective osteotomies. A three-week period post-surgery was given to allow for healing to take place after which all three sheep were euthanized and the ilia were collected. Samples were prepared, qualitatively and quantitatively analyzed using histology micrographs and image analysis software (ImageJ, NIH, Bethesda, MD). Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were quantified to evaluate the osseointegration parameters. RESULTS: All implants exhibit successful bone formation in the peri-implant environment as well as within the open spaces of the trabecular network. Osseointegration within the TM (quantified by %BIC) as a function of drilling technique was more pronounced in OD samples(p>0.05). The %BAFO however shows a significant difference (p=0.036) between the CCW and R samples. Greater bone volume and frequency of bone chips are observed in OD samples. CONCLUSION: The utilization of OD as a design for improved fixation of hardware was supported by increased levels of stability, both primary and secondary. Histological data with OD provided notably different results from those of the regular drilling method.

The genetic landscape of mitochondrial diseases in the next-generation sequencing era: a Portuguese cohort study.

Introduction: Rare disorders that are genetically and clinically heterogeneous, such as mitochondrial diseases (MDs), have a challenging diagnosis. Nuclear genes codify most proteins involved in mitochondrial biogenesis, despite all mitochondria having their own DNA. The development of next-generation sequencing (NGS) technologies has revolutionized the understanding of many genes involved in the pathogenesis of MDs. In this new genetic era, using the NGS approach, we aimed to identify the genetic etiology for a suspected MD in a cohort of 450 Portuguese patients. Methods: We examined 450 patients using a combined NGS strategy, starting with the analysis of a targeted mitochondrial panel of 213 nuclear genes, and then proceeding to analyze the whole mitochondrial DNA. Results and Discussion: In this study, we identified disease-related variants in 134 (30%) analyzed patients, 88 with nuclear DNA (nDNA) and 46 with mitochondrial DNA (mtDNA) variants, most of them being pediatric patients (66%), of which 77% were identified in nDNA and 23% in mtDNA. The molecular analysis of this cohort revealed 72 already described pathogenic and 20 novel, probably pathogenic, variants, as well as 62 variants of unknown significance. For this cohort of patients with suspected MDs, the use of a customized gene panel provided a molecular diagnosis in a timely and cost-effective manner. Patients who cannot be diagnosed after this initial approach will be further selected for whole-exome sequencing. Conclusion: As a national laboratory for the study and research of MDs, we demonstrated the power of NGS to achieve a molecular etiology, expanding the mutational spectrum and proposing accurate genetic counseling in this group of heterogeneous diseases without therapeutic options.

Angiogenic biomarkers and healing of living cellular constructs.

The use of intra-oral soft-tissue-engineered devices has demonstrated potential for oral mucosa regeneration. The aim of this study was to investigate the temporal expression of angiogenic biomarkers during wound healing of soft tissue reconstructive procedures comparing living cellular constructs (LCC) with autogenous free gingival grafts. Forty-four human participants bilaterally lacking sufficient zones of attached keratinized gingiva were randomly assigned to soft tissue surgery plus either LCC or autograft. Wound fluid samples were collected at baseline and weeks 1, 2, 3, and 4 post-operatively and analyzed for a panel of angiogenic biomarkers: angiogenin (ANG), angiostatin (ANT), PDGF-BB, VEGF, FGF-2, IL-8, TIMP-1, TIMP-2, GM-CSF, and IP-10. Results demonstrated a significant increase in expression of ANT, PDGF-BB, VEGF, FGF-2, and IL-8 for the LCC group over the autograft group at the early stages of wound repair. Although angiogenic biomarkers were modestly elevated for the LCC group, no clinical correlation with wound healing was found. This human investigation demonstrates that, during early wound-healing events, expression of angiogenic-related biomarkers is up-regulated in sites treated with LCC compared with autogenous free gingival grafts, which may provide a safe and effective alternative for regenerating intra-oral soft tissues (ClinicalTrials.gov number, NCT01134081).

Perfusión miocárdica SPECT con prueba de frío como predictor de desarrollo de isquemia de esfuerzo en el seguimiento de pacientes asintomáticos con riesgo cardiovascular moderado / Cold Pressor Test Myocardial Perfusion SPECT as a Predictor of the Development of Ischemia at Exercise in the Follow up of Asymptomatic Patients with Moderate Cardiovascular Risk

Introducción Estudios previos han publicado la correlación entre defectos de perfusión miocárdica (PM) SPECT durante la prueba de frío (PF) y la acetilcolina intracoronaria y su utilidad como marcador independiente de disfunción endotelial (DE). Objetivo Analizar la incidencia de positivización de los estudios de PM de esfuerzo en el seguimiento de pacientes asintomáticos con riesgo cardiovascular (CV) moderado y DE detectada con la PF. Material y métodos De 301 pacientes del Registro PARADIGMA (PM SPECT esfuerzo normal y probabilidad clínica < 20% de eventos a 10 años [riesgo moderado por índice de Framingham]), 55 tuvieron PF positiva (+) (18,3%). Se analizaron en forma prospectiva y consecutiva 15 pacientes asintomáticos con PF (+) y un grupo control (GC) de 15 pacientes con PF negativa (-), con apareamiento de sexo, edad y factores de riesgo coronario (FRC), que cumplieron un seguimiento de 12 ± 2 meses, en quienes se realizó una nueva PM SPECT de reposo y esfuerzo. Se utilizó un score de extensión de PM en un modelo de 17 segmentos. Se analizaron los FRC y la incidencia de isquemia en la PM de esfuerzo de seguimiento en cada grupo. Resultado Edad: PF (-) 57,3 ± 8,9 versus TF (+) 52,5 ± 7,5 (p = 0,09). Positivizaron la PM de esfuerzo: grupo PF (+) 5/15: 33,3% y 0 del GC (p = 0,04). Sin diferencias estadísticamente significativas en los FRC entre ambos grupos. Conclusiones Una PM SPECT anormal durante la PF en pacientes asintomáticos con riesgo CV moderado diferenció a aquellos pacientes que positivizaron los estudios de PM de esfuerzo a un año de seguimiento y no hubo estudios anormales en el grupo control.

Introduction Previous studies have published the correlation between myocardial perfusion SPECT (MP) during cold pressor test (CPT) and intracoronary acetylcholine and its usefulness as independent marker of endothelial dysfunction (ED). Objective To analyze the incidence of positivization of MP exercise studies in the follow up of asymptomatic patients with moderate cardiovascular risk (CV) and ED detected by PF. Material and Methods Of 301 patients of the PARADIGMA Registry (normal exercise MP SPECT and clinical probability < 20% of events at 10 years [moderate risk by Framingham index] 55 had positive PF (+) (18.3%). Prospectively and consecutively, 15 asymptomatic patients with PF (+), and a control group (CG) of 15 patients with negative PF, with paired sex, age and coronary risk factors (CRF), that accomplished a 12 ± 2 months follow up, and that underwent a new exercise and resting MP SPECT were analyzed. An MP extension score was used in a model of 17 segments. The CRF and the incidence of ischemia during follow up exercise MP of each group were assessed. Results Age: PF (-) 57.3 ± 8.9 versus TF (+) 52.5 ± 7.5 (p = 0,09). Positivized the exercise MP: PF group (+) 5/15: 33.3% and 0 in the CG (p=0.04). No statistically significant differences between CRF in both groups. Conclusions An abnormal MP SPECT during PF in asymptomatic patients with moderate CV risk differentiated those patients who positivized exercise MP studies at one year follow up and there were no abnormal studies in the control group.

Valvuloplastia mitral y tricuspídea en una paciente con estenosis bivalvular / Mitral and tricuspid valvuloplasty in a patient with bivalve stenosis

Se presenta el caso de una mujer de 43 años, con antecedentes de fiebre reumática, accidente vasculoencefálico isquémico, estenosis mitral y tricuspídea y disnea en CF III de 2 años de evolución. Se realizó ecocardiografia transesofágica que demostró estenosis mitral severa con área de 0,78 cm² y estenosis tricuspídea severa, con índice de Wilkins de 9/16. Se realizó valvuloplastia bivalvular percutánea con balón, con resultado exitoso. A un año del procedimiento la paciente evoluciona asintomática.