The Effect of Alendronate on Subsidence After Lateral Transpsoas Interbody Fusion: A Preliminary Report.

BACKGROUND: Success after lateral transpsoas interbody fusion (LLIF) partially depends on avoidance of subsidence to maintain spinal alignment, disc space height, and indirect neural decompression. Techniques for preventing subsidence have focused largely on surgical and biomechanical properties of spinal reconstruction; however, medical management may also affect subsidence rates as well. The purpose of this study is to examine the effect of alendronate on minimally invasive LLIF patients with regard to radiographic and catastrophic subsidence. METHODS: We followed 26 patients who had LLIF at the L4-5 level (13 on alendronate, 13 control) and 22 patients at the L3-4 level (10 on alendronate, 12 control). Radiographs were reviewed to obtain measurements of subsidence at the 4 corners of the cage at 3 follow-up time points (2-3, 5-8, and 10-12 months). A Tobit mixed model was used to confirm the results. RESULTS: We found no relationship between alendronate and subsidence for L3-4 fusion. At L4-5 we observed increased subsidence in the control group compared to the alendronate group (difference = 0.07 cm, 95% confidence interval [CI]: -0.01, 0.16, P = .08). There was a decrease in subsidence noted for the alendronate group for each time period (differences: 2-3: -0.06 cm, 95% CI: -0.28, 0.15], P = .27; 5-8: -0.14 cm, 95% CI: -0.36, .08, P = .10; 10-12: -0.21 cm, 95% CI: -0.48, .04, P = .05). CONCLUSIONS: A clear reduction in subsidence was found with the use of postoperative alendronate in patients undergoing L4-5 LLIF. Alendronate had a significant decrease in subsidence at L4-5 after 10-12 months as compared to the control group. Additionally, no patients treated with alendronate had catastrophic subsidence. These data suggest the need for further study of alendronate in the prevention of subsidence after LLIF. LEVEL OF EVIDENCE: 3.

Identifying the Risk of Swallowing-Related Pulmonary Complications in Older Patients With Hip Fracture.

To identify and potentially modify the risk of pulmonary complications in a group of older patients with hip fracture, the authors obtained speech and language pathology consultations for these patients. Then they performed a retrospective chart review of all patients 65 years and older who were admitted to their institution between June 2011 and July 2013 with acute hip fracture, were treated surgically, and had a speech and language pathology evaluation in the immediate perioperative period. The authors identified 52 patients who met the study criteria. According to the American Society of Anesthesiologists (ASA) classification system, at the time of surgery, 1 patient (2%) was classified as ASA I, 12 patients (23%) were ASA II, 26 (50%) were ASA III, and 12 (23%) were ASA IV. Based on a speech and language pathology evaluation, 22 patients (42%) were diagnosed with dysphagia. Statistical analysis showed that ASA III status and ASA IV status were meaningful predictors of dysphagia and that dysphagia itself was a strong risk factor for pulmonary aspiration, pneumonia, and aspiration pneumonitis. Evaluation by a speech and language pathologist, particularly of patients classified as ASA III or ASA IV, may be an efficient means of averting pulmonary morbidity that is common in older patients with hip fracture.

Comparative cytogenetic characterization of primary canine melanocytic lesions using array CGH and fluorescence in situ hybridization.

Melanocytic lesions originating from the oral mucosa or cutaneous epithelium are common in the general dog population, with up to 100,000 diagnoses each year in the USA. Oral melanoma is the most frequent canine neoplasm of the oral cavity, exhibiting a highly aggressive course. Cutaneous melanocytomas occur frequently, but rarely develop into a malignant form. Despite the differential prognosis, it has been assumed that subtypes of melanocytic lesions represent the same disease. To address the relative paucity of information about their genomic status, molecular cytogenetic analysis was performed on the three recognized subtypes of canine melanocytic lesions. Using array comparative genomic hybridization (aCGH) analysis, highly aberrant distinct copy number status across the tumor genome for both of the malignant melanoma subtypes was revealed. The most frequent aberrations included gain of dog chromosome (CFA) 13 and 17 and loss of CFA 22. Melanocytomas possessed fewer genome wide aberrations, yet showed a recurrent gain of CFA 20q15.3-17. A distinctive copy number profile, evident only in oral melanomas, displayed a sigmoidal pattern of copy number loss followed immediately by a gain, around CFA 30q14. Moreover, when assessed by fluorescence in situ hybridization (FISH), copy number aberrations of targeted genes, such as gain of c-MYC (80 % of cases) and loss of CDKN2A (68 % of cases), were observed. This study suggests that in concordance with what is known for human melanomas, canine melanomas of the oral mucosa and cutaneous epithelium are discrete and initiated by different molecular pathways.

Genetic heterogeneity beyond CYP2C8*3 does not explain differential sensitivity to paclitaxel-induced neuropathy.

The development of paclitaxel-induced peripheral neuropathy (PIPN) is influenced by drug exposure and patient genetics. The purpose of this analysis was to expand on a previous reported association of CYP2C8*3 and PIPN risk by investigating additional polymorphisms in CYP2C8 and in hundreds of other genes potentially relevant to paclitaxel pharmacokinetics. Clinical data was collected prospectively in an observational registry of newly diagnosed breast cancer patients. Patients treated with paclitaxel-containing regimens were genotyped using the Affymetrix DMET™ Plus chip. Patients who carried the CYP2C8*2, *3, or *4 variant were collapsed into a low-metabolizer CYP2C8 phenotype for association with PIPN. Separately, all SNPs that surpassed quality control were assessed individually and as a composite of genetic ancestry for associations with PIPN. 412 paclitaxel-treated patients and 564 genetic markers were included in the analysis. The risk of PIPN was significantly greater in the CYP2C8 low-metabolizer group (HR = 1.722, p = 0.018); however, the influences of the *2 and *4 SNPs were not independently significant (*2: p = 0.847, *4: p = 0.408). One intronic SNP in ABCG1 (rs492338) surpassed the exploratory significance threshold for an association with PIPN in the Caucasian cohort (p = 0.0008) but not in the non-Caucasian replication group (p = 0.54). Substantial genetic variability was observed within self-reported racial groups but this genetic variability was not associated with risk of grade 2+ PIPN. The pharmacogenetic heterogeneity within a cohort of breast cancer patients is dramatic, though we did not find evidence that this heterogeneity directly influences the risk of PIPN beyond the contribution of CYP2C8*3.