The perioperative cost of Infuse bone graft in posterolateral lumbar spine fusion.

BACKGROUND CONTEXT: There is mounting evidence supporting the efficacy of bone morphogenetic protein (BMP) for both anterior interbody and posterolateral lumbar fusion. However, the relative cost of BMP remains an important concern for physicians, hospitals, and payers. PURPOSE: The purpose of this study is to report on the perioperative costs for patients treated with rhBMP-2 as compared with an iliac crest bone graft (ICBG) supplemented with graft extenders. STUDY DESIGN/SETTING: A prospective randomized controlled trial of rhBMP-2/ACS (Infuse Bone Graft; Medtronic Sofamor Danek, Memphis, TN) versus ICBG+/-graft extender for lumbar spine fusion in patients over 60 years old. PATIENT SAMPLE: One hundred two patients over 60 years old who required a posterolateral lumbar spine fusion randomized between receiving rhBMP-2/ACS or ICBG. OUTCOME MEASURES: All health-care costs over the first 3 months after surgery. METHODS: As part of a prospective randomized trial of rhBMP-2/ACS versus ICBG+/-graft extender for lumbar spine fusion, all costs over the first 3 months after surgery were directly recorded by a dedicated coder funded by Norton Healthcare, Louisville, KY. A dedicated research nurse also followed all patients throughout their hospital stay and posthospitalization recovery to identify any adverse events or additional outpatient medical care. RESULTS: Fifty patients received rhBMP-2/ACS and 52 underwent ICBG harvest. The mean hospital cost for the index admission was $24,736 for the rhBMP-2/ACS group and $21,138 for the ICBG group. Mean inpatient physician costs were $5,082 in the rhBMP-2/ACS group and $5,316 in the ICBG group. Costs associated with posthospital rehabilitation averaged $4,906 in the rhBMP-2/ACS group versus $6,820 in the ICBG group. Total payer expenditure for the 3-month perioperative period averaged $33,860 in the rhBMP-2/ACS group and $37,227 in the ICBG group. CONCLUSIONS: The hospital carries the cost burden associated with the utilization of rhBMP-2/ACS. In contrast, the payer in a Diagnosis-Related Group (DRG) model achieves a net savings, based primarily on the decreased payment for inpatient rehabilitation, but also on decreased hospital reimbursement, physician costs, and other outpatient services.     

Predictive Factors and Patterns of Recurrence in Patients with Triple Negative Breast Cancer

Background

We investigated the outcomes of patients with triple negative breast cancer ([TNBC] = estrogen receptor negative, progesterone receptor negative, and HER2 nonamplified).

Methods

We identified 414 patients with stage I–III TNBC treated between 1999 and 2008. Data included patient/tumor characteristics, surgical, systemic, and radiation treatment received, and breast cancer-specific survival. Data were compared using Chi square, Fisher exact test, and logistic regression. A p value <.05 was considered significant.

Results

The cohort included 414 patients (mean age 53.8 ± 12.5 years) with a mean follow-up of 68.2 ± 36.4 months. Of 414 patients, 304 (73.4 %) had no evidence of recurrence, while 110 (26.6 %) had recurrent disease, including 19 (17.3 %) with isolated locoregional recurrence, 70 (63.6 %) with isolated distant recurrence, and 21 (19.1 %) with both. Of 91 patients with distant recurrences, lung was most common (n = 38), followed by brain (n = 32), bone (n = 31), and liver (n = 29). Factors significantly associated with recurrence included increasing tumor size, positive nodal status, increasing stage, and type of chemotherapy (adjuvant vs neoadjuvant). After controlling for all potential confounders in multivariate stepwise regression, these same factors were also found to be independent predictors of recurrence. In the survival analysis, these same factors, in addition to receipt of radiation were found to be predictive of survival.

Conclusions

Approximately 25 % of patients with TNBC experienced a locoregional and/or distant recurrence, resulting in greater than 75 % breast cancer-specific mortality for those who experienced a distant recurrence. The lack of targeted therapy for this aggressive breast cancer subtype likely contributed to this finding.     

A Retrospective Review of Histopathologic Features Associated with Increased Risk of Recurrence of Non-melanoma Skin Cancer After Mohs Micrographic Surgery

ObjectiveMohs micrographic surgery (MMS) is the gold standard treatment for non-melanoma skin cancer (NMSC). However, NMSC recurrence may occur in a small proportion of patients. The aim of this study was to identify histopathologic features seen on the final stage of previous MMS, which may increase the risk of NMSC recurrence.MethodsThis was a single-institution retrospective study of 39 recurrent basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), which were treated with MMS. Slides from the final stage of previous MMS were reviewed by two board-certified dermatopathologists for the following histopathologic features: perineural inflammation, dense inflammation, mucin, ruptured follicle, actinic keratosis, and missing tissue.ResultsTwenty recurrent BCCs and 19 recurrent SCCs were included. Histopathologic features identified on the final stage of previous MMS included missing tissue from the epidermis, dermis, and/or subcutis (69%), actinic keratosis (51%), perineural inflammation (10%), and dense inflammation (8%). Ruptured follicle was present in one BCC case, and mucin was not identified in any cases.LimitationsLimitations include retrospective study design, small number of recurrent cases, single institution, and lack of a control group consisting of NMSC cases which did not recur after MMS.ConclusionMohs surgeons should carefully evaluate NMSC frozen sections for the presence of missing tissue, actinic keratosis, perineural inflammation, and dense inflammation as these histopathologic features may be associated with tumor recurrence. It is of paramount importance to acquire high quality frozen sections for thorough margin evaluation.     

Menkes Disease Mimicking Child Abuse

Althouygh Menkes disease has well‐recognized neurologic, developmental, and cutaneous features, the initial presentation may resemble child abuse. We describe a 5‐month‐old boy with multiple fractures indicative of nonaccidental trauma who was ultimately diagnosed with Menkes disease. Copper deficiency leads to connective tissue abnormalities and may result in subdural hematomas, wormian bones, cervical spine defects, rib fractures, and spurring of the long bone metaphyses. Several of these findings, including fractures and subdural hematomas, may be misinterpreted as child abuse.     

Interferon regulatory factor 6 is necessary, but not sufficient, for keratinocyte differentiation

Regulation of epidermal proliferation and differentiation is critical for maintenance of cutaneous homeostasis. Interferon Regulatory Factor 6 (Irf6)-deficient mice die perinatally and exhibit ectopic proliferation and defective epidermal differentiation. We sought to determine whether these disruptions of epidermal function were cell autonomous, and used embryonic Irf6(-/-) keratinocytes to understand the specific role of Irf6 in keratinocyte proliferation and differentiation. In the absence of Irf6, keratinocytes exhibited a heterogeneous phenotype with the presence of large cells. Irf6(-/-) keratinocytes displayed increased colony-forming efficiency compared with wild-type cells, suggesting that Irf6 represses long-term proliferation. Irf6 was present at low levels in wild-type keratinocytes in culture, and upregulated after induction of differentiation in vitro, along with upregulation of markers of early differentiation. However, Irf6(-/-) keratinocytes did not express markers of terminal differentiation. Overexpression of Irf6 in wild-type keratinocytes was insufficient to induce expression of markers of differentiation under growing conditions. Together, these results indicated that Irf6 is necessary, but not sufficient, for keratinocyte differentiation. Finally, using a transgenic mouse expressing Lac-Z under the regulation of an enhancer element 9.7 kb upstream of the Irf6 start site, we demonstrated that this element contributes to the regulation of Irf6 in the epidermis and keratinocytes in culture.     

Cortical evolution in mammals: the bane and beauty of phenotypic variability

Evolution by natural selection, the unifying theory of all biological sciences, provides a basis for understanding how phenotypic variability is generated at all levels of organization from genes to behavior. However, it is important to distinguish what is the target of selection vs. what is transmitted across generations. Physical traits, behaviors, and the extended phenotype are all selected features of an individual, but genes that covary with different aspects of the targets of selection are inherited. Here we review the variability in cortical organization, morphology, and behavior that have been observed across species and describe similar types of variability within species. We examine sources of variability and the constraints that limit the types of changes that evolution has and can produce. Finally, we underscore the importance of how genes and genetic regulatory networks are deployed and interact within an individual, and their relationship to external, physical forces within the environment that shape the ultimate phenotype.     

Innovations in osteomyelitis research: A review of animal models

Infection of bone tissue, or osteomyelitis, has become a growing concern in modern healthcare due in no small part to a rise in antibiotic resistance among bacteria, notably Staphylococcus aureus. The current standard of care involves aggressive, prolonged antibiotic therapy combined with surgical debridement of infected tissues. While this treatment may be sufficient for resolving a portion of cases, recurrences of the infection and associated risks including toxicity with long‐term antibiotic usage have been reported. Therefore, there exists a need to produce safer, more efficacious options of treatment for osteomyelitis. In order to test treatment regimens, animal models that closely mimic the clinical condition and allow for accurate evaluation of therapeutics are necessary. Establishing a model that replicates features of osteomyelitis in humans continues to be a challenge to scientists, as there are many variables involved, including choosing an appropriate species and method to establish infection. This review addresses the refinement of animal models of osteomyelitis to reflect the clinical disease and test prospective therapeutics. The aim of this review is to explore studies regarding the use of animals for osteomyelitis therapeutics research and encourage further development of such animal models for the translation of results from the animal experiment to human medicine.     

Acute stress-mediated increases in extracellular glutamate levels in the rat amygdala: differential effects of antidepressant treatment

Depressive illness is associated with changes in amygdalar volume, and stressful life events are known to precipitate depressive episodes in this patient population. Stress affects amygdalar synaptic plasticity and several neurotransmitter systems have been implicated in stress-mediated changes in the brain, including the glutamatergic system. However, the role of the glutamatergic system in stress-mediated plasticity in the amygdala remains to be determined. Accordingly the current study examined the stress modulation of extracellular glutamate levels in the basolateral nucleus (BLA) and the central nucleus (CeA) of the amygdala by in vivo microdialysis. Acute stress increased extracellular glutamate levels in the BLA and CeA, although the dynamics of these stress-mediated changes were dramatically different in these amygdalar nuclei. Tetrodotoxin administration reduced basal, and completely eliminated stress-mediated increases in glutamate efflux in the amygdala, demonstrating that stress effects are dependent on local axonal depolarization. Moreover, stress-mediated increases in glutamate efflux in the BLA were inhibited by the antidepressant tianeptine but not by the selective serotonin-reuptake inhibitor fluoxetine. Collectively, these data demonstrate that stress-induced modulation of glutamate neurochemistry reflects a fundamental pathological change that may contribute to the aetiology and progression of depressive illness, and suggest that some antidepressants such as tianeptine may elicit their clinical effects by modulation of glutamatergic neurotransmission.