Vascular calcification and mineral bone disorder in chronic kidney disease

Chronic Kidney Disease (CKD), osteoporosis and mild hyponatremia are all prevalent chronic conditions that may coexist and are often under-recognized. Mineral-Bone Disorder begins early in the natural history of CKD and results in complex abnormalities of bone which ultimately confers a well-established increased risk of fragility fractures in End Stage Kidney Disease. Hyponatremia is a novel, usually renal mediated metabolic perturbation, that most commonly occurs independently of the stage of renal dysfunction but which may also predispose to increased fracture risk. The extent -if any- to which either early stages of renal dysfunction or the presence of hyponatremia contribute to fracture occurrence in the general population, independently of osteoporosis, is unclear. Renal transplantation is the treatment of choice for ESKD and although it restores endogenous renal function it typically fails to normalize either the long term cardiovascular or fracture risk. One potential mechanism contributing to these elevated long-term risks and to diminished Health Related Quality of Life is persistent, post-transplant hyperparathyroidism. In this study we retrospectively examine the association of renal function and serum sodium with Bone Mineral Density and fracture occurrence in a retrospective cohort of 1930 female members of the general population who underwent routine DXA scan. We then prospectively recruited a cohort of 90 renal transplant recipients in order to examine the association of post transplant parathyroid hormone (PTH) level with measures of CKD Mineral Bone Disorder, including, DXA Bone Mineral Density, Vascular Calcification (assessed using both abdominal radiography and CT techniques, as well as indirectly by carotid-femoral Pulse Wave Velocity) and Quality of Life (using the Short Form-12 and a PTH specific symptom score). In the retrospective DXA cohort, moderate CKD (eGFR 30-59ml/min/1.73m2) and hyponatremia (<135mmol/L) were associated with fracture occurrence, independently of BMD, with an adjusted Odds Ratio (95% Confidence Interval), of 1.37 (1.0, 1.89) and 2.25 (1.24, 4.09) respectively. In the renal transplant study, PTH was independently associated with the presence of osteoporosis, adjusted Odds Ratio (95% Confidence Interval), 1.15 (per 10ng/ml increment), (1.04, 1.26). The presence of osteoporosis but not PTH was independently associated with measures of vascular calcification, adjusted ß (95% Confidence Interval), 12.45, (1.16, 23.75). Of the eight quality-of-life domains examined, post-transplant PTH (per 10ng/ml increment), was only significantly and independently associated with reduced Physical Functioning, (95% Confidence Interval), 1.12 (1.01, 1.23). CKD and hyponatremia are both common health problems that may contribute to fracture occurrence in the general population, a major on-going public health concern. PTH and decreased Bone Mineral Density may signal sub-optimal long-term outcomes post renal transplantation, influencing bone and vascular health and to a limited extent long term Health Related Quality of Life

Role of the fibula in the stability of diaphyseal tibial fractures fixed by intramedullary nailing

Background: For tibial fractures, the decision to fix a concomitant fibular fracture is undertaken on a case-by-case basis. To aid in this clinical decision-making process, we investigated whether loss of integrity of the fibula significantly destabilises midshaft tibial fractures, whether fixation of the fibula restores stability to the tibia, and whether removal of the fibula and interosseous membrane for expediency in biomechanical testing significantly influences tibial interfragmentary mechanics. Methods: Tibia/fibula pairs were harvested from six cadaveric donors with the interosseous membrane intact. A tibial osteotomy fracture was fixed by reamed intramedullary (IM) nailing. Axial, torsion, bending, and shear tests were completed for four models of fibular involvement: intact fibula, osteotomy fracture, fibular plating, and resected fibula and interosseous membrane. Findings: Overall construct stiffness decreased slightly with fibular osteotomy compared to intact bone, but this change was not statistically significant. Under low loads, the influence of the fibula on construct stability was only statistically significant in torsion (large effect size). Fibular plating stiffened the construct slightly, but this change was not statistically significant compared to the fibular osteotomy case. Complete resection of the fibula and interosseous membrane significantly decreased construct torsional stiffness only (large effect size). Interpretation: These results suggest that fixation of the fibula may not contribute significantly to the stability of diaphyseal tibial fractures and should not be undertaken unless otherwise clinically indicated. For testing purposes, load-sharing through the interosseous membrane contributes significantly to overall construct mechanics, especially in torsion, and we recommend preservation of these structures when possible.

Optimizing perioperative analgesia for patients undergoing operative fixation of hip fractures

This PhD thesis describes work carried out on investigation of various interventions with the aim to optimise the anaesthetic management of patients scheduled to undergo operative fixation of hip fractures. We analysed the perioperative effects of continuous femoral nerve block, single preoperative dose of i.v. dexamethasone, the intention to deposit local anaesthetic in different locations around the femoral nerve during ultrasound guided femoral nerve block, continuous spinal anaesthesia and peri-surgical site infiltration with local anaesthetic after surgical fixation of hip fractures. Continuous femoral nerve block provided more effective preoperative analgesia six hours after the insertion of the perineural catheter compared to a standard opiate-based regimen in patients undergoing operative fixation of fractured hip. A single low dose of preoperative dexamethasone in the intervention group decreased pain scores by 75% six hours after the surgery. Both interventions had no major effect on the functional recovery in the first year after the surgical fixation of fractured hip. The results of the ultrasound guided femoral nerve block trial showed no clinical advantage of intending to deposit local anaesthetic circumferentially during performing femoral nerve block. Using the Dixon and Massey’s “up- and-down” method, we demonstrated that intrathecal 0.26 ml of 0.5% bupivacaine provided adequate surgical anaesthesia within 15 minutes in 50% of patients undergoing operative fixation of hip fracture. Finally, we demonstrated that local anaesthetic infiltration had no effect on pain scores 12 hours after the surgical fixation of fractured neck of femur. In addition to this original body of work, a review article was published on femoral nerve block highlighting the use of ultrasound guidance. In conclusion, the results of this thesis offer an insight into interventions aimed at optimising perioperative analgesia in patients scheduled to undergo operative fixation of hip fractures.

Skin and bone: the face in the archaeological imagination

Thirteen unique archaeological countenances from Ireland were produced through the Manchester method of facial reconstruction. Their gaze prompts a space for a broad discourse regarding the face found within human and artefactual remains of Ireland. These faces are reminders of the human element which is at the core of the discipline of archaeology. These re-constructions create a voyeuristic relationship with the past. At once sating a curiosity about the past, facial reconstructions also provide a catharsis to our presently situated selves. As powerful visual documents, archaeological facial reconstructions illustrate re-presentations of the past as well as how the present can be connected to the past. Through engagment with Emmanuel Levinas’s (1906- 1995) main philosophical themes, the presence of the face is examined in a diachronic structure. The ‘starting point’ is the Neolithic period which has been associated with the notion of visuality with a reconstruction from the early Neolithic site of Annagh, Co. Limerick. The following layer of analysis appears with attention to intersubjectivity in the early medieval period with facial reconstructions from Dooey, Co. Donegal and Owenbristy, Co. Galway. Building upon the past concepts, the late medieval period is associated with the notion of alterity and paired with faces from Ballinderry, Co. Kildare and a sample of males from Gallen Priory, Co. Offaly. The final layer of examination culminates with the application of response and respons-ibility to the post-medieval Irish landscape with facial reconstructions from the prison on Spike Island, Co. Cork. These layers of investigation are similar to the stratigraphical composition of both the archaeological landscape and the skeletal/soft tissue landscape of the face. The separation of the neglected phenomenon of the face from the overwhelming embrace of the field of craniometrics is necessary. Through this detachment a new manner in which to discuss the face and its place within the (bio)archaeological record is possible. Encountering the faces seen in mortuary contexts, material culture, and archaeological facial reconstructions, inform and shape the archaeological imagination.