Ezequiel Goldschmidt

The effect of vancomycin powder on human dural fibroblast culture and its implications for dural repair during spine surgery

OBJECTIVE Surgical site infections (SSIs) are a major source of morbidity after spinal surgery. Several recent studies have described the finding that applying vancomycin powder to the surgical bed may reduce the incidence of SSI. However, applying vancomycin in high concentrations has been shown in vitro to inhibit osteoblast proliferation and to induce cell death. Vancomycin may have a deleterious effect on dural healing after repair of an intentional or unintentional durotomy. This study was therefore undertaken to assess the effect of different concentrations of vancomycin on a human dura mater cell culture. METHODS Human dura intended for disposal after decompressive craniectomy was harvested. Explant primary cultures and subcultures were subsequently performed. Cells were characterized through common staining and immunohistochemistry. A growth curve was performed to assess the effect of different concentrations of vancomycin (40, 400, and 4000 μg/ml) on cell count. The effect of vancomycin on cellular shape, intercellular arrangement, and viability was also evaluated. RESULTS All dural tissue samples successfully developed into fusiform cells, demonstrating pseudopod projections and spindle formation. The cells demonstrated vimentin positivity and also had typical features of fibroblasts. When applied to the cultures, the highest dose of vancomycin induced generalized cell death within 24 hours. The mean (± SD) cell counts for control, 40, 400, and 4000 μg/ml were 38.72 ± 15.93, 36.28 ± 22.87, 19.48 ± 6.53, and 4.07 ± 9.66, respectively (p < 0.0001, ANOVA). Compared with controls, vancomycin-exposed cells histologically demonstrated a smaller cytoplasm and decreased pseudopodia formation resulting in the inhibition of normal spindle intercellular arrangement. CONCLUSIONS When vancomycin powder is applied locally, dural cells are exposed to a concentration several times greater than when delivered systemically. In this in vitro model, vancomycin induced dural cell death, inhibited growth, and altered cellular morphology in a concentration-dependent fashion. Defining a safe vancomycin concentration that is both bactericidal and also does not inhibit normal dural healing is necessary.

Polyetheretherketone interbody cages versus autogenous iliac crest bone grafts with anterior fixation for cervical disc disease.

Objective: The aim of this study was to compare the fusion rate, operation time, recovery of disc space height, clinical duration and improvement, return to activities of daily living, and complication rate associated with anterior cervical discectomy with interbody fusion by using polyetheretherketone cages or autogenous iliac crest bone grafts as disc replacement in a series of 60 patients. Materials and Methods: Between November 2006 and February 2010 a retrospective analytical observational cohort study was carried out in 60 consecutive patients surgically treated with anterior cervical discectomy with interbody fusion for degenerative disc desease at the Neurosurgical Department of the Hospital Italiano de Buenos Aires. The patients were divided into 2 groups for the assessment of clinical characteristics, demographics, fusion rates, duration of surgical procedure, neurological and functional outcomes, imaging results, and complications. Group A included patients treated with autogenous iliac crest bone grafts, and group B included patients treated with polyetheretherketone cages. Results: The mean age of the patients was 50.8 years. Female patients comprised the majority in both groups (63.3%). Cervicobrachialgia was the most common presentation. Clinical improvement, fusion rates, and recovery of disc space height were similar in both groups. The operation time was significantly shorter in the polyetheretherketone group (P<0.001). Twenty percent (n=6) of the patients in group A suffered complications, >80% of which were associated with iliac crest bone graft harvesting. Patients in group B had no complications (P<0.05). Conclusions: Although outcomes were very successful in both groups in terms of fixation stability, recovery of disc space, return to activities of daily living and work, and remission of symptoms, operation time was considerably shorter for patients in the polyetheretherketone group, who had none of the complications associated with iliac crest bone graft harvesting, both differences being statistically significant.

Evaluation of a Hybrid Dynamic Stabilization and Fusion System in the Lumbar Spine: A 10 Year Experience.

Introduction: The development of adjacent-segment disease is a recognized consequence of lumbar fusion surgery. Posterior dynamic stabilization, or motion preservation, techniques have been developed which theoretically decrease stress on adjacent segments following fusion. This study presents the experience of using a hybrid dynamic stabilization and fusion construct for degenerative lumbar spine pathology in place of rigid arthrodesis. Methods: A clinical cohort investigation was conducted of 66 consecutive patients (31 female, 35 male; mean age: 53 years, range: 25 – 76 years) who underwent posterior lumbar instrumentation with the Dynesys Transition Optima (DTO) implant (Zimmer-Biomet Spine, Warsaw, IN) hybrid dynamic stabilization and fusion system over a 10-year period. The median length of follow-up was five years. DTO consists of pedicle screw fixation coupled to a rigid rod as well as a flexible longitudinal connecting system. All patients had symptoms of back pain and neurogenic claudication refractory to non-surgical treatment. Patients underwent lumbar arthrodesis surgery in which the hybrid system was used for stabilization instead of arthrodesis of the stenotic adjacent level. Results: Indications for DTO instrumentation were primary degenerative disc disease (n = 52) and failed back surgery syndrome (n = 14). The most common dynamically stabilized and fused segments were L3-L4 (n = 37) and L5-S1 (n = 33), respectively. Thirty-eight patients (56%) underwent decompression at the dynamically stabilized level, and 57 patients (86%) had an interbody device placed at the level of arthrodesis. Complications during the follow-up period included a single case of screw breakage and a single case of pseudoarthrosis. Ten patients (15%) subsequently underwent conversion of the dynamic stabilization portion of their DTO instrumentation to rigid spinal arthrodesis. Conclusion: The DTO system represents a novel hybrid dynamic stabilization and fusion construct. This 10-year experience found the device to be highly effective as well as safe. The technique may serve as an alternative to multilevel arthrodesis. Implantation of a motion-preserving dynamic stabilization device immediately adjacent to a fused level instead of extending a rigid construct may reduce the subsequent development of adjacent-segment disease in this patient population.

Pathological changes of the hippocampus and cognitive dysfunction following frontal lobe surgery in a rat model.

BackgroundPostoperative cognitive dysfunction (POCD) is a known complication after intracranial surgery. Impaired hippocampal neurogenesis has been associated with cognitive dysfunction in animal models.MethodsIn order to assess hippocampal changes after brain surgery, a frontal lobe corticectomy was performed in ten adult Wistar rats (group 4). Three different control groups (n = 10 each) included no treatment (G1), general anesthesia alone (G2), and craniectomy without dural opening (G3). Twenty-four hours after surgery, half of the animals were killed, and the mRNA levels for IL-6, TNF-α, and brain-derived growth factor (BDNF) in the contralateral hippocampus were assessed by qPCR. Seven days later, the remaining animals underwent anxiety and memory testing. Afterwards, the number of immature neurons in the hippocampal cortex was measured by doublecortin (DCX) staining.ResultsTwenty-four hours after surgery, mRNA levels of IL-6 and TNF-α increased and BDNF decreased in both surgical groups G3 and G4 (p = 0.012). Cognitive tests demonstrated an increase in anxiety levels and memory impairment in surgical groups compared with non-surgical animals. These changes correlated with an inhibition of hippocampal neurogenesis evidenced by a decreased number of new neurons (mean ± SD for G1-4: 66.4 ± 24; 57.6 ± 22.2; 21.3 ± 3.78; 5.7 ± 1.05, p < 0.001, non-parametric ANOVA).ConclusionsIntracranial surgery was demonstrated to induce an inflammatory reaction within the hippocampus that compromised neurogenesis and impaired normal cognitive processing. Corticectomy had a greater effect than craniotomy alone, indicating a central trigger for hippocampal inflammatory changes. POCD after craniotomy may originate from a central inflammatory response resulting from surgical trauma to the brain parenchyma.

Assessing the role of selected growth factors and cytostatic agents in an in vitro model of human dura mater healing.

Abstract Objectives: Cerebrospinal fluid (CSF) leaks are a common concern in skull base surgery. Appropriate dural healing is crucial to prevent CSF leaks but the entire process has been barely understood so far. Here, we review the impact of growth factors and chemotherapeutic agents on an explant culture of human dural fibroblasts and a 3D subculture grown in a collagen mesh scaffold. Methods: Human dural specimens were harvested during surgical procedures where they would not be further used therapeutically or diagnostically. Explant cultures were grown in Petri dishes, and subcultures were grown in collagen mesh scaffolds. Insulin, fibroblast growth factor type 2 (FGF-2), and human serum were analyzed for their effect as growth factors, whereas mitomycin C, vincristine, and colchicine were analyzed for their role as inhibitors. Cell count was used as a parameter to assess the effects of these factors. In addition, the effects of human serum were assessed using collagen mesh scaffolds. Results: Insulin, FGF-2, and human serum increased culture cell count; human serum also achieved an increased number of viable fibroblasts embedded in a collagen mesh. Mitomycin C, which is a mitosis inhibitor, showed no significant effect on cell count, whereas colchicine and vincristine, which inhibit both mitosis and migration, resulted in cell growth suppression. Discussion: In our model, dural defect closure is achieved through cell migration rather than through cell growth. Adding growth factors to the dural suture line or into a collagen mesh might prove useful to stimulate dural closure.

Cirugía transnasal endoscópica para tumores de hipófisis

Introducción: Exponer la técnica utilizada y los resultados obtenidos en los primeros 52 pacientes portadores de tumores hipofisarios tratados por la vía endoscópica transnasal en el Hospital Italiano de Buenos Aires Métodos: Se llevó a cabo un análisis retrospectivo de 52 cirugías endoscópicas transnasales utilizadas en el tratamiento de tumores hipofisários. Las mismas fueron realizadas en el Hospital Italiano de Buenos Aires durante el período junio del 2011 a junio del 2012. Se analizaron las características demográficas de los pacientes, la patología de base y la morbimortalidad asociada a la cirugía. Resultados: La edad media de los pacientes fue de 41,52 años con un rango de 18-79. La distribución fue similar entre hombres y mujeres. Las patologías más frecuentes fueron: adenomas no funcionantes (40.4%), tumores productores de GH/Acromegalia (25%) y tumores productores de ACTH/Enfermedad de Cushing (23.1%). Aproximadamente el 70 % correspondieron a macroadenomas. Sólo un paciente presentó complicaciones. No se registro ningún óbito. Conclusión: Si bien podremos objetivar fehacientemente resultados más concluyentes en futuros trabajos, podemos decir a priori que, en la endoscopía el detalle anatómico es claramente superior al microscópico y que la posibilidad de la introducción del endoscopio en la silla turca permite la visualización directa de remanentes tumorales, de sitios de fístula y como así también de la glándula normal, ventajas que potencialmente podrían permitir obtener mejores resultados quirúrgicos, en términos de control de la enfermedad y tasa de complicaciones.

Design and Testing of 2 Novel Scores That Predict Global Sagittal Alignment Utilizing Cervical or Lumbar Plain Radiographs

BACKGROUND Global sagittal deformity is an established cause of disability. However, measurements of sagittal alignment are often ignored when patients present with symptoms localizing to the cervical or lumbar spine. OBJECTIVE To develop scoring scales to predict the risk of sagittal malalignment in patients with only cervical or lumbar spine radiographs. METHODS A retrospective review of a prospectively maintained multicenter adult spinal deformity database was performed. Primary outcome (sagittal malalignment) was defined as a C7 plumbline ≥ 50 mm. Two multivariate logistic regressions were performed using patient characteristics and measurements derived from cervical or lumbar radiographs as covariates. Point scores were assigned to age, body mass index (BMI), and lumbar lordosis or T1 slope by rounding their &bgr; coefficients to the nearest integer. RESULTS Nine hundred seventy‐nine patients were included, with 652 randomly assigned to the derivation cohort (used to build the score) and 327 comprising the validation set. Final cervical score for the primary outcome included BMI ≥ 25 (1 point), age ≥ 55 yr (2 points), and T1 slope ≥ 27o (2 points). Final lumbar score for the primary outcome included BMI ≥ 25 (1 point), age ≥ 55 yr (1 point), and lumbar lordosis ≥ 45o (-1 points). High scores for both the cervical and lumbar spine presented with high specificity and positive likelihood ratios of sagittal malalignment. CONCLUSION We developed scoring scales to predict global sagittal malalignment utilizing clinical covariates and cervical or lumbar radiographs. Patients with high scores may prompt imaging with long‐cassette plain films to evaluate for global sagittal imbalance.

Construction and in vitro testing of a cellulose dura mater graft

Introduction: Cerebrospinal fluid (CSF) leaks are a common complication after cranial and spinal surgery and are associated with increased morbidity. Despite continuous research in this field, this problem is far from solved. In this paper, we describe the construction and testing of a bacterial cellulose (BC) membrane as a new dural patch. Materials and Methods: The synthesis of BC was performed using Gluconacetobacter hansenii (ATCC 23769) and films were sterilized by autoclaving. The membranes were seeded with human dural fibroblasts. Growth, shape, and cell viability were assessed after 4 weeks. Results: Normally shaped fibroblasts were seen on the BC grafts; confocal microscopy showed cells inside the structure of the mesh. Both viable and nonviable cells were present. Cellular attachment and viability were confirmed by replating of the membranes. Discussion: BC membranes are used in clinical practice to improve skin healing. In the presence of water, they form an elastic, nontoxic, and resistant biogel that can accommodate collagen and growth factors within their structure, thus BC is a good candidate for dural graft construction.

Low preoperative serum prealbumin levels and the postoperative surgical site infection risk in elective spine surgery: a consecutive series

OBJECTIVENutritional deficiency negatively affects outcomes in many health conditions. In spine surgery, evidence linking preoperative nutritional deficiency to postoperative surgical site infection (SSI) has been limited to small retrospective studies. Authors of the current study analyzed a large consecutive cohort of patients who had undergone elective spine surgery to determine the relationship between a serum biomarker of nutritional status (preoperative prealbumin levels) and SSI.METHODSThe authors conducted a retrospective review of the electronic medical charts of patients who had undergone posterior spinal surgeries and whose preoperative prealbumin level was available. Additional data pertinent to the risk of SSI were also collected. Patients who developed a postoperative SSI were identified, and risk factors for postoperative SSI were analyzed. Nutritional deficiency was defined as a preoperative serum prealbumin level ≤ 20 mg/dl.RESULTSAmong a consecutive series of 387 patients who met the study criteria for inclusion, the infection rate for those with preoperative prealbumin ≤ 20 mg/dl was 17.8% (13/73), versus 4.8% (15/314) for those with preoperative prealbumin > 20 mg/dl. On univariate and multivariate analysis a low preoperative prealbumin level was a risk factor for postoperative SSI with a crude OR of 4.29 (p < 0.01) and an adjusted OR of 3.28 (p = 0.02). In addition, several previously known risk factors for infection, including diabetes, spinal fusion, and number of operative levels, were significant for the development of an SSI.CONCLUSIONSIn this consecutive series, preoperative prealbumin levels, a serum biomarker of nutritional status, correlated with the risk of SSI in elective spine surgery. Prehabilitation before spine surgery, including strategies to improve nutritional status in patients with nutritional deficiencies, may increase value and improve spine care.

Early Results of Microsurgical Treatment of Acromegaly

Abstract Purpose Acromegaly is an unusual disorder caused by abnormal oversecretion of growth hormone by pituitary adenomas. Transsphenoidal surgery is frequently the first management option. The objective of this article is to establish the effectiveness of a transnasal transsphenoidal approach in the treatment of GH-producing adenomas, and to identify risk factors for disease persistence. Methods We conducted a retrospective review of 81 patients treated for acromegaly with transsphenoidal microsurgery between 2006 and 2010. Results Macroadenomas accounted for 66.7% of the cases, contrast-enhanced MRI revealing cavernous sinus invasion in 28.4% of the patients (23 subjects). Cure was achieved in 72.8% (59 of 82). All microadenomas (27 cases) were managed effectively with surgery whereas cure rates stood at 66.7% for macroadenomas. Monovariate analysis showed that disease persistence was statistically associated with three variables. Odds ratio for remission stood at 1.68 for microadenomas and 0.033 for cavernous sinus invasion (p<0.001). Preoperative GH values were statistically associated with cure during follow up (p<0.05). Multivariate logistic regression analysis showed that only cavernous sinus invasion continued to be significantly associated with disease persistence (OR 3.52, p<0.05). Conclusion The transnasal approach proves effective in the treatment and cure of acromegaly. Cavernous sinus invasion is a major predictor of disease persistence.