Stromal-derived factor-1?/CXCL12-CXCR4 chemotactic pathway promotes perineural invasion in pancreatic cancer.

By London Spine
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Stromal-derived factor-1α/CXCL12-CXCR4 chemotactic pathway promotes perineural invasion in pancreatic cancer.

Oncotarget. 2015 Mar 10;6(7):4717-32

Authors: Xu Q, Wang Z, Chen X, Duan W, Lei J, Zong L, Li X, Sheng L, Ma J, Han L, Li W, Zhang L, Guo K, Ma Z, Wu Z, Wu E, Ma Q

Abstract
Perineural invasion (PNI) is considered as an alternative route for the metastatic spread of pancreatic cancer cells; however, the molecular changes leading to PNI are still poorly understood. In this study, we show that the CXCL12/CXCR4 axis plays a pivotal role in the neurotropism of pancreatic cancer cells to local peripheral nerves. Immunohistochemical staining results revealed that CXCR4 elevation correlated with PNI in 78 pancreatic cancer samples. Both in vitro and in vivo PNI models were applied to investigate the function of the CXCL12/CXCR4 signaling in PNI progression and pathogenesis. The results showed that the activation of the CXCL12/CXCR4 axis significantly increased pancreatic cancer cells invasion and promoted the outgrowth of the dorsal root ganglia. CXCL12 derived from the peripheral nerves stimulated the invasion and chemotactic migration of CXCR4-positive cancer cells in a paracrine manner, eventually leading to PNI. In vivo analyses revealed that the abrogation of the activated signaling inhibited tumor growth and invasion of the sciatic nerve toward the spinal cord. These data indicate that the CXCL12/CXCR4 axis may be a novel therapeutic target to prevent the perineural dissemination of pancreatic cancer.

PMID: 25605248 [PubMed – indexed for MEDLINE]

Reconstruction of the denuded nasoseptal flap donor site with a free fascia lata graft: technical note.

By London Spine
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Reconstruction of the denuded nasoseptal flap donor site with a free fascia lata graft: technical note.

Eur Arch Otorhinolaryngol. 2016 Mar 7;

Authors: Zeinalizadeh M, Sadrehosseini SM, Barkhoudarian G, Carrau RL

Abstract
The nasoseptal flap provides hearty vascularized tissue for the reconstruction of skull base defects subsequent to expanded endonasal approaches; however, it leads to exposure of the cartilage at the septal donor site producing crusting and discomfort while it remucosalizes. We report an alternative technique to reconstruct the denuded nasal septal donor site by means of a free fascia lata graft. Fascia lata grafting of the nasoseptal flap donor site showed evidence of revascularization 4 weeks after initial surgery. Re-epithelialization was complete 4-12 weeks postoperation. Although the nasoseptal flap provides a versatile reconstructive technique, its harvest results in significant donor site morbidity. A free fascia lata graft accelerates the rate of donor site remucosalization; thus, decreasing the nasal complications.

PMID: 26951218 [PubMed – as supplied by publisher]

Hip Stiffness Patterns in Lumbar Flexion or Extension-Based Movement Syndromes.

By London Spine

Hip Stiffness Patterns in Lumbar Flexion or Extension-Based Movement Syndromes.

Arch Phys Med Rehabil. 2014 Oct 10;

Authors: Zafereo J, Devanna R, Mulligan E, Wang-Price S

Abstract
OBJECTIVE: To determine whether a relationship exists between sagittal plane hip range of motion (ROM) loss and sagittal plane lumbar Movement System Impairment (MSI) categories in patients with low back pain (LBP).
DESIGN: Correlational study SETTING: University outpatient physical therapy clinic PARTICIPANTS: Forty subjects with LBP INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: Classification into a flexion- or extension-based lumbar MSI category, and bilateral passive hip flexion and extension ROM testing. Using pre-defined criteria, subjects in each MSI category were sub-classified into one of three hip stiffness categories: (1) a considerable loss of either flexion or extension (pattern A), (2) a considerable loss of both flexion and extension (pattern B), or (3) minimally limited flexion or extension (pattern C).
RESULTS: Pattern A occurred in 23 (57.5%) of the subjects, with the primary direction of hip motion loss agreeing with the MSI category 78.3% of the time (φ=.56, P=.007). Pattern B occurred in 10 (25%) of the subjects, with the primary direction of hip motion loss agreeing with the MSI category 70% of the time (φ=.47, P=.197). Pattern C occurred in 7 (17.5%) of the subjects, with the primary direction of hip motion limitation agreeing with the MSI category 42.9% of the time (φ=-.40, P=.290).
CONCLUSIONS: Considerable unidirectional hip motion loss in the sagittal plane was a common finding among subjects with LBP and yielded a strong positive relationship with the same direction MSI category. These results may inform future studies investigating whether treatment of hip stiffness patterns could improve outcomes in LBP management.

PMID: 25312581 [PubMed – as supplied by publisher]

Role of peripheral sigma-1 receptors in ischaemic pain: Potential interactions with ASIC and P2X receptors.

By London Spine
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Role of peripheral sigma-1 receptors in ischaemic pain: Potential interactions with ASIC and P2X receptors.

Eur J Pain. 2015 Sep 11;

Authors: Kwon SG, Roh DH, Yoon SY, Choi SR, Choi HS, Moon JY, Kang SY, Kim HW, Han HJ, Beitz AJ, Oh SB, Lee JH

Abstract
BACKGROUND: The role of peripheral sigma-1 receptors (Sig-1Rs) in normal nociception and in pathologically induced pain conditions has not been thoroughly investigated. Since there is mounting evidence that Sig-1Rs modulate ischaemia-induced pathological conditions, we investigated the role of Sig-1Rs in ischaemia-induced mechanical allodynia (MA) and addressed their possible interaction with acid-sensing ion channels (ASICs) and P2X receptors at the ischaemic site.
METHODS: We used a rodent model of hindlimb thrombus-induced ischaemic pain (TIIP) to investigate their role. Western blot was performed to observe changes in Sig-1R expression in peripheral nervous tissues. MA was measured after intraplantar (i.pl.) injections of antagonists for the Sig-1, ASIC and P2X receptors in TIIP rats or agonists of each receptor in naïve rats.
RESULTS: Sig-1R expression significantly increased in skin, sciatic nerve and dorsal root ganglia at 3 days post-TIIP surgery. I.pl. injections of the Sig-1R antagonist, BD-1047 on post-operative days 0-3 significantly attenuated the development of MA during the induction phase, but had no effect on MA when given during the maintenance phase (days 3-6 post-surgery). BD-1047 synergistically increased amiloride (an ASICs blocker)- and TNP-ATP (a P2X antagonist)-induced analgesic effects in TIIP rats. In naïve rats, i.pl. injection of Sig-1R agonist PRE-084 alone did not produce MA; but it did induce MA when co-administered with either an acidic pH solution or a sub-effective dose of αβmeATP.
CONCLUSION: Peripheral Sig-1Rs contribute to the induction of ischaemia-induced MA via facilitation of ASICs and P2X receptors. Thus, peripheral Sig-1Rs represent a novel therapeutic target for the treatment of ischaemic pain.

PMID: 26358747 [PubMed – as supplied by publisher]

Effects of Anterior Plating on Clinical Outcomes of Anterior Lumbar Interbody Fusion.

By London Spine
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Effects of Anterior Plating on Clinical Outcomes of Anterior Lumbar Interbody Fusion.

J Spinal Disord Tech. 2012 Dec 3;

Authors: Snyder LA, Kalb S, Kakarla UK, Porter RW, Kaibara T, Dickman CA, Theodore N

Abstract
STUDY DESIGN:: Retrospective Revie. OBJECTIVE:: To compare surgical outcomes of patients who have undergone anterior lumbar interbody fusion (ALIF) with and without plating. SUMMARY OF BACKGROUND DATA:: In biomechanical testing, ALIF constructs supplemented with plating (ALIFP) reduce range of motion and increase construct stiffness compared to ALIF alone. However, whether ALIFP constructs translate into improved clinical outcomes over ALIF alone is unknown. METHODS:: From 2004 through 2010, 231 patients underwent ALIF with (146) or without (85) plating. Eight patients lost to follow up were excluded from final evaluation. Patients’ records were evaluated retrospectively for demographics, complications, and outcomes. RESULTS:: At a mean follow-up of 13.7 months (range 1-108▒mo), the mean Economic, Functional, and Total Prolo scores for ALIF patients were 4.23, 3.63, and 7.87, respectively. The mean Oswestry Disability Index (ODI) was 24%. At a mean follow-up of 11.2 months (range 1-93▒mo), the mean Economic, Functional, and Total Prolo scores for ALIFP patients were 4.28, 3.67, and 7.95, respectively. The mean ODI was 22.9%. There was no significant difference between rate of complications or Prolo scores or ODI between the two groups (t-test). Neither diabetes, hypertension, smoking, gender, nor age greater than 55 years was significantly related to whether patients had higher Prolo scores with or without plating. Patients with a normal body mass index (BMI) and ALIF had significantly better Prolo Economic scores and Total scores than patients with a normal BMI and ALIFP (P=0.04 and 0.02, independent samples t-test). Patients were also stratified by surgical indication for surgery, and there was no significant difference in Prolo Scores or ODI for patients who underwent ALIF alone versus ALIFP. CONCLUSIONS:: Even when stratified by indication for surgery, anterior plating does not appear to improve Prolo scores or ODI, suggesting that not all patients undergoing ALIF require plating.

PMID: 23222098 [PubMed – as supplied by publisher]

Automated Detection, Localization, and Classification of Traumatic Vertebral Body Fractures in the Thoracic and Lumbar Spine at CT.

By London Spine
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Automated Detection, Localization, and Classification of Traumatic Vertebral Body Fractures in the Thoracic and Lumbar Spine at CT.

Radiology. 2016 Jan;278(1):64-73

Authors: Burns JE, Yao J, Muñoz H, Summers RM

Abstract
PURPOSE: To design and validate a fully automated computer system for the detection and anatomic localization of traumatic thoracic and lumbar vertebral body fractures at computed tomography (CT).
MATERIALS AND METHODS: This retrospective study was HIPAA compliant. Institutional review board approval was obtained, and informed consent was waived. CT examinations in 104 patients (mean age, 34.4 years; range, 14-88 years; 32 women, 72 men), consisting of 94 examinations with positive findings for fractures (59 with vertebral body fractures) and 10 control examinations (without vertebral fractures), were performed. There were 141 thoracic and lumbar vertebral body fractures in the case set. The locations of fractures were marked and classified by a radiologist according to Denis column involvement. The CT data set was divided into training and testing subsets (37 and 67 subsets, respectively) for analysis by means of prototype software for fully automated spinal segmentation and fracture detection. Free-response receiver operating characteristic analysis was performed.
RESULTS: Training set sensitivity for detection and localization of fractures within each vertebra was 0.82 (28 of 34 findings; 95% confidence interval [CI]: 0.68, 0.90), with a false-positive rate of 2.5 findings per patient. The sensitivity for fracture localization to the correct vertebra was 0.88 (23 of 26 findings; 95% CI: 0.72, 0.96), with a false-positive rate of 1.3. Testing set sensitivity for the detection and localization of fractures within each vertebra was 0.81 (87 of 107 findings; 95% CI: 0.75, 0.87), with a false-positive rate of 2.7. The sensitivity for fracture localization to the correct vertebra was 0.92 (55 of 60 findings; 95% CI: 0.79, 0.94), with a false-positive rate of 1.6. The most common cause of false-positive findings was nutrient foramina (106 of 272 findings [39%]).
CONCLUSION: The fully automated computer system detects and anatomically localizes vertebral body fractures in the thoracic and lumbar spine on CT images with a high sensitivity and a low false-positive rate.

PMID: 26172532 [PubMed – indexed for MEDLINE]