Nonoperative Modalities to Treat Symptomatic Cervical Spondylosis

Cervical spondylosis is a common and disabling condition. It is generally felt that the initial management should be nonoperative, and these modalities include physiotherapy, analgesia and selective nerve root injections. Surgery should be reserved for moderate to severe myelopathy patients who have failed a period of conservative treatment and patients whose symptoms are not adequately controlled by nonoperative means. A review of the literature supporting various modalities of conservative management is presented, and it is concluded that although effective, nonoperative treatment is labour intensive, requiring regular review and careful selection of medications and physical therapy on a case by case basis

Pheochromocytoma presenting as recurrent urinary tract infections : a case report

<p>Abstract</p> <p>Introduction</p> <p>Pheochromocytomas are rare, potentially fatal, neuroendocrine tumors of the adrenal medulla or extra-adrenal paraganglia. Their clinical presentation varies greatly from the classic triad of episodic headache, diaphoresis and tachycardia to include a spectrum of non-specific symptomatology.</p> <p>Case presentation</p> <p>A 43-year-old Caucasian woman was referred to us from primary care services with a three-month history of recurrent urinary tract infections on a background of hypertension, latent autoimmune diabetes of adulthood and autoimmune hypothyroidism. At 38 years she required insulin therapy. Despite medication compliance and dietary control, she reported a recent history of increased insulin requirements and uncontrolled hypertension with concomitant recurrent urinary tract infections. A renal ultrasound examination, to rule out underlying renal pathology, revealed an incidental 8cm right adrenal mass of both solid and cystic components. A subsequent computed tomography of her abdomen and pelvis confirmed a solid heterogeneous mass consistent with a pheochromocytoma. There were no other features suggestive of multiple endocrine neoplasia. Urinary collection over 24 hours revealed grossly elevated levels of catecholamines and metabolites. Following an open right adrenalectomy, our patient's insulin requirements were significantly reduced and her symptoms resolved. Two weeks post-operatively, an iodine-131-metaiodobenzylguanidine scintigraphy was negative for residual tumor and metastatic disease. Urinary catecholamine and metabolite concentrations were within the normal range at a follow-up six months later.</p> <p>Conclusion</p> <p>Pheochromocytoma is a rare catecholamine-producing tumor requiring a high index of suspicion for early diagnosis. Our case report serves to highlight the importance of considering pheochromocytoma as a differential diagnosis in the atypical setting of recurrent urinary tract infections and concomitant autoimmune disease.</p

Indocyanine green fluorescence angiography: A critical intra-operative assessment tool to aid decision making in complex hand trauma

Indocyanine green fluorescence angiography (ICG-FA) is a validated non-invasive imaging tool used to assess tissue perfusion and guide intra-operative decision making in many surgical disciplines. Clinical assessment of tissue perfusion following crush or degloving traumatic hand injuries presents a significant challenge. This case report supports the critical role of intra-operative ICG-FA as a decision aid in complex hand trauma. We propose ICG-FA will minimise unnecessary tissue debridement, negating complex soft tissue reconstructive surgery and ultimately expediting tissue healing and return to function for hand trauma patients.A 35-year-old right hand dominant manual labourer presented to the emergency department after sustaining a crush injury to his right hand. Examination under anaesthetic revealed a comminuted open fracture of middle finger P2 with compromised soft tissue coverage. A formal assessment of hand perfusion was performed using a triad of clinical assessment, critical judgement and ICG-FA. The ICG-FA revealed a small skin flap affecting the dorsoradial P2 skin which was not perfused. This prompted meticulous minimal debridement of this tissue and prevented unnecessary over-debridement that would have resulted in complex soft tissue reconstruction.Currently the gold standard assessment for tissue perfusion in hand injuries is clinical judgement and is limited by subjective interobserver error [1]. IGA-FA has been proven to offer a real time assessment of tissue perfusion. This case demonstrates the use of ICG-FA as an adjunct to clinical examination and judgement, to optimise the accuracy of soft tissue perfusion assessment in complex hand trauma

Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer

Background: Although omic-based discovery approaches can provide powerful tools for biomarker identification, several reservations have been raised regarding the clinical applicability of gene expression studies, such as their prohibitive cost. However, the limited availability of antibodies is a key barrier to the development of a lower cost alternative, namely a discrete collection of immunohistochemistry (IHC)-based biomarkers. The aim of this study was to use a systematic approach to generate and screen affinity-purified, mono-specific antibodies targeting progression-related biomarkers, with a view towards developing a clinically applicable IHC-based prognostic biomarker panel for breast cancer. Methods: We examined both in-house and publicly available breast cancer DNA microarray datasets relating to invasion and metastasis, thus identifying a cohort of candidate progression-associated biomarkers. Of these, 18 antibodies were released for extended analysis. Validated antibodies were screened against a tissue microarray (TMA) constructed from a cohort of consecutive breast cancer cases (n = 512) to test the immunohistochemical surrogate signature. Results: Antibody screening revealed 3 candidate prognostic markers: the cell cycle regulator, Anillin (ANLN); the mitogen-activated protein kinase, PDZ-Binding Kinase (PBK); and the estrogen response gene, PDZ-Domain Containing 1 (PDZK1). Increased expression of ANLN and PBK was associated with poor prognosis, whilst increased expression of PDZK1 was associated with good prognosis. A 3-marker signature comprised of high PBK, high ANLN and low PDZK1 expression was associated with decreased recurrence-free survival (p &lt; 0.001) and breast cancer-specific survival (BCSS) (p &lt; 0.001). This novel signature was associated with high tumour grade (p &lt; 0.001), positive nodal status (p = 0.029), ER-negativity (p = 0.006), Her2-positivity (p = 0.036) and high Ki67 status (p &lt; 0.001). However, multivariate Cox regression demonstrated that the signature was not a significant predictor of BCSS (HR = 6.38; 95% CI = 0.79-51.26, p = 0.082). Conclusions: We have developed a comprehensive biomarker pathway that extends from discovery through to validation on a TMA platform. This proof-of-concept study has resulted in the identification of a novel 3-protein prognostic panel. Additional biochemical markers, interrogated using this high-throughput platform, may further augment the prognostic accuracy of this panel to a point that may allow implementation into routine clinical practice

Systematic antibody generation and validation via tissue microarray technology leading to identification of a novel protein prognostic panel in breast cancer

Background: Although omic-based discovery approaches can provide powerful tools for biomarker identification, several reservations have been raised regarding the clinical applicability of gene expression studies, such as their prohibitive cost. However, the limited availability of antibodies is a key barrier to the development of a lower cost alternative, namely a discrete collection of immunohistochemistry (IHC)-based biomarkers. The aim of this study was to use a systematic approach to generate and screen affinity-purified, mono-specific antibodies targeting progression-related biomarkers, with a view towards developing a clinically applicable IHC-based prognostic biomarker panel for breast cancer. Methods: We examined both in-house and publicly available breast cancer DNA microarray datasets relating to invasion and metastasis, thus identifying a cohort of candidate progression-associated biomarkers. Of these, 18 antibodies were released for extended analysis. Validated antibodies were screened against a tissue microarray (TMA) constructed from a cohort of consecutive breast cancer cases (n = 512) to test the immunohistochemical surrogate signature. Results: Antibody screening revealed 3 candidate prognostic markers: the cell cycle regulator, Anillin (ANLN); the mitogen-activated protein kinase, PDZ-Binding Kinase (PBK); and the estrogen response gene, PDZ-Domain Containing 1 (PDZK1). Increased expression of ANLN and PBK was associated with poor prognosis, whilst increased expression of PDZK1 was associated with good prognosis. A 3-marker signature comprised of high PBK, high ANLN and low PDZK1 expression was associated with decreased recurrence-free survival (p &lt; 0.001) and breast cancer-specific survival (BCSS) (p &lt; 0.001). This novel signature was associated with high tumour grade (p &lt; 0.001), positive nodal status (p = 0.029), ER-negativity (p = 0.006), Her2-positivity (p = 0.036) and high Ki67 status (p &lt; 0.001). However, multivariate Cox regression demonstrated that the signature was not a significant predictor of BCSS (HR = 6.38; 95% CI = 0.79-51.26, p = 0.082). Conclusions: We have developed a comprehensive biomarker pathway that extends from discovery through to validation on a TMA platform. This proof-of-concept study has resulted in the identification of a novel 3-protein prognostic panel. Additional biochemical markers, interrogated using this high-throughput platform, may further augment the prognostic accuracy of this panel to a point that may allow implementation into routine clinical practice

Risk analysis of blood transfusion requirements in emergency and elective spinal surgery

Spinal surgery has long been considered to have an elevated risk of perioperative blood loss with significant associated blood transfusion requirements. However, a great variability exists in the blood loss and transfusion requirements of differing patients and differing procedures in the area of spinal surgery. We performed a retrospective study of all patients undergoing spinal surgery who required a transfusion ≥1 U of red blood cells (RBC) at the National Spinal Injuries Unit (NSIU) at the Mater Misericordiae University Hospital over a 10-year period. The purpose of this study was to identify risk factors associated with significant perioperative transfusion allowing the early recognition of patients at greatest risk, and to improve existing transfusion practices allowing safer, more appropriate blood product allocation. 1,596 surgical procedures were performed at the NSIU over a 10-year period. 25.9% (414/1,596) of these cases required a blood transfusion (n = 414). Surgical groups with a significant risk of requiring a transfusion >2 U RBC included deformity surgery (RR = 3.351, 95% CI 1.123–10.006, p = 0.03), tumor surgery (RR = 3.298, 95% CI 1.078–10.089, p = 0.036), and trauma surgery (RR = 2.444, 95% CI 1.183–5.050, p = 0.036). Multivariable logistic regression analysis identified multilevel surgery (>3 levels) as a significant risk of requiring a transfusion >2 U RBC (RR = 4.682, 95% CI 2.654–8.261, p < 0.0001). Several risk factors in the spinal surgery patient were identified as corresponding to significant transfusion requirements. A greater awareness of the risk factors associated with transfusion is required in order to optimize patient management