Outcomes following staged bilateral total hip replacement: does first-side surgery predict the second?

INTRODUCTION: Patient-reported outcome measures (PROMs) for bilateral staged total hip replacements (THRs) were reviewed to determine whether first-side surgery can predict second-side outcomes. METHODS: A retrospective review was undertaken of a consecutive cohort of staged bilateral THRs using the same approach, implant and technique, from August 2009 to February 2020. Minimal important change (MIC) in PROMs was set at ≥5. RESULTS: A total of 296 consecutive staged bilateral THRs were performed in 148 patients. Mean time interval between sides was 25 months (range 2-102). Mean age was 63.2 years for the first side and 65.3 years for the second; 62.8% of patients were female. Mean body mass index was 31.08 for the first side, increasing to 31.57 for the second side (p = 0.248). One-year follow-up PROMs were available for 96.6% and 92.5% of the first and second side, respectively. Mean PROMs improvement at 1 year was 26.4 for the first side and 25.1 for the second side (p = 0.207). Some 97.9% of patients achieved MIC for the first side and 96.3% for the second side (p = 0.092). Eight patients failed to reach an MIC on one side, all were female (p < 0.001); however, MIC was achieved for the contralateral side. Seven of eight patients (87.5%) achieved MIC by 2 years. CONCLUSIONS: This study identified no significant difference between first- and second-side PROMs improvements following staged bilateral THRs at 1-year follow-up. Failure to reach MIC on one side does not preclude success on the other. Female patients were more prone to not reach MIC at 1 year, but improvement was still subsequently achieved in the majority of cases. The informed consent process is able to reflect this expectation.

Debridement, antibiotics and implant retention (DAIR) following hip and knee arthroplasty: results and findings of a multidisciplinary approach from a non-specialist prosthetic infection centre.

INTRODUCTION: Prosthetic joint infection (PJI) is a catastrophic complication following arthroplasty surgery. Recently a debridement, antibiotics and implant retention (DAIR) procedure has gained popularity for PJI where a thorough debridement, irrigation and modular component exchange is undertaken. METHOD: We present the outcome for DAIR, data collected prospectively, in a busy orthopaedic unit but not one specialising in PJI. All patients with PJI were included without loss of data or patients from 2012 to 2018 with a minimum follow-up of 5 years. RESULTS: Four total knee replacements, 17 total hip replacements, one revision total hip replacement and three hip hemiarthroplasties are included with an average duration from onset of symptoms to the DAIR procedure of 11 days (range 1-22 days). Staphylococcus aureus (24%) and Staphylococcus epidermidis (32%) were the most common causative organisms, and the most common antibiotic regimens included intravenous teicoplanin and flucloxacillin. Average follow-up was 67 months (range 9-104 months). Only four patients went on to require revision surgery. An analysis of midterm patient outcome measures for 6 of the total hip replacement (THR) DAIR patients were compared with a database of 792 THRs (with a minimum two-year follow-up) carried out by the same surgeon revealed no significant difference in Oxford hip scores at one-year post-surgery (OHS DAIR 36.2 vs 39 for control group). CONCLUSION: This study includes 25 consecutive patients treated with DAIR with only one reinfection, with a mean follow-up period of 5 years. Using a strict protocol, DAIR appears to offer a successful treatment strategy for the management of early PJI.

Synthetic Strategy Towards Heterodimetallic Half-Sandwich Complexes Based on a Symmetric Ditopic Ligand.

Multimetallic complexes have been shown in several examples to possess greater anticancer activity than their monometallic counterparts. The increased activity has been attributed to altered modes of action. We herein report the synthesis of a series of heterodimetallic compounds based on a ditopic ligand featuring 2-pyridylimine chelating motifs and organometallic half-sandwich moieties. The complexes were characterized by a combination of 1H NMR spectroscopy, electrospray ionization mass spectrometry, elemental analysis and single crystal X-ray diffraction. Investigations into the stability of representative complexes in DMSO-d 6 and 10% DMSO-d 6 /D2O revealed the occurrence of solvent-chlorido ligand exchange. Proliferation assays in four human cancer cell lines showed that the Os-Rh complex possessed minimal activity, while all other complexes were inactive.

Phase shift and correlation coefficient measurement of cerebral autoregulation during deep breathing in traumatic brain injury (TBI).

BACKGROUND: Impairment of cerebral autoregulation is known to adversely affect outcome following traumatic brain injury (TBI). The phase shift (PS) method of cerebral autoregulation (CA) assessment describes the time lag between fluctuations in arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV) in the middle cerebral artery. An alternative method (Mx-ABP) is based on the statistical correlation between ABP and CBFV waveforms over time. We compared these two indices in a cohort of severely head injured patients undergoing controlled, 6-breaths-per-minute ventilation. METHODS: PS and Mx-ABP were calculated from 33 recordings of CBFV and MAP in 22 patients with TBI. Spearman's correlation coefficient was used to assess the agreement between PS and Mx-ABP. The relationship between ICP slow wave amplitude, MAP slow wave amplitude and mean ICP was also examined. FINDINGS: Mean values for Mx-ABP and PS were 0.44 +/- 0.27, and 49 +/- 26 (degrees), respectively. PS correlated significantly with Mx-ABP (r = -0.648, p < 0.001). A Bland-Altman plot of normalised Mx-ABP and Phase Shift values showed no significant bias or relationship (mean difference = 0.0004, r = -0.037, p = 0.852). During the test procedure, ICP fluctuated in an approximately sinusoidal fashion, with a mean amplitude of 4.96 +/- 2.72 mmHg (peak to peak). The magnitude of ICP fluctuation during deep breathing correlated weakly but significantly with mean ICP (r = 0.391, p < 0.05) and with the amplitude of ABP fluctuations (r = 0.625, p < 0.0005). CONCLUSIONS: Phase shift and Mx-ABP in TBI are well correlated. Deep breathing presents as an effective tool with which to assess autoregulation using the phase shift method.

Sonic hedgehog regulates branching morphogenesis in the mammalian lung.

The mammalian lung, like many other organs, develops by branching morphogenesis of an epithelium [1]. Development initiates with evagination of two ventral buds of foregut endoderm into the underlying splanchnic mesoderm. As the buds extend, they send out lateral branches at precise, invariant positions, establishing the primary airways and the lobes of each lung. Dichotomous branching leads to further extension of the airways. Grafting studies have demonstrated the importance of bronchial mesenchyme in inducing epithelial branching, but the significance of epithelial signaling has largely been unstudied. The morphogen Sonic hedgehog (Shh) is widely expressed in the foregut endoderm and is specifically upregulated in the distal epithelium of the lung where branching is occurring [2]. Ectopic expression of Shh disrupts branching and increases proliferation, suggesting that local Shh signaling regulates lung development [2]. We report here that Shh is essential for development of the respiratory system. In Shh null mutants, we found that the trachea and esophagus do not separate properly and the lungs form a rudimentary sac due to failure of branching and growth after formation of the primary lung buds. Interestingly, normal proximo-distal differentiation of the airway epithelium occurred, indicating that Shh is not needed for differentiation events. In addition, the transcription of several mesenchymally expressed downstream targets of Shh is abolished. These results highlight the importance of epithelially derived Shh in regulating branching morphogenesis of the lung.

Sonic hedgehog signaling is essential for hair development.

BACKGROUND: The skin is responsible for forming a variety of epidermal structures that differ amongst vertebrates. In each case the specific structure (for example scale, feather or hair) arises from an epidermal placode as a result of epithelial-mesenchymal interactions with the underlying dermal mesenchyme. Expression of members of the Wnt, Hedgehog and bone morphogenetic protein families (Wnt10b, Sonic hedgehog (Shh) and Bmp2/Bmp4, respectively) in the epidermis correlates with the initiation of hair follicle formation. Further, their expression continues into either the epidermally derived hair matrix which forms the hair itself, or the dermal papilla which is responsible for induction of the hair matrix. To address the role of Shh in the hair follicle, we have examined Shh null mutant mice. RESULTS: We found that follicle development in the Shh mutant embryo arrested after the initial epidermal-dermal interactions that lead to the formation of a dermal papilla anlage and ingrowth of the epidermis. Wnt10b, Bmp2 and Bmp4 continued to be expressed at this time, however. When grafted to nude mice (which lack T cells), Shh mutant skin gave rise to large abnormal follicles containing a small dermal papilla. Although these follicles showed high rates of proliferation and some differentiation of hair matrix cells into hair-shaft-like material, no hair was formed. CONCLUSIONS: Shh signaling is not required for initiating hair follicle development. Shh signaling is essential, however, for controlling ingrowth and morphogenesis of the hair follicle.

Dynamic cerebral autoregulation: should intracranial pressure be taken into account?

BACKGROUND: Although the inclusion of cerebral perfusion pressure (CPP) is a standard feature in static testing of autoregulation after head injury, controversy surrounds the use of CPP versus arterial blood pressure (ABP) in dynamic tests. The aim of our project was to assess the discrepancies between methods of dynamic autoregulation testing based on CPP or ABP, and study possible differences in their prognostic value. METHOD: Intermittent recordings of intracranial pressure (ICP), ABP and middle cerebral artery blood flow velocity (FV) waveforms were made in 151 anaesthetised and ventilated adult head injured patients as part of their required care. Indices of dynamic autoregulation were calculated as a moving correlation coefficient of 60 samples (total time 3 min) of 6 s mean values of FV and ABP (Mxa) or FV and CPP (Mx). Values of Mx and Mxa were averaged over multiple recordings in each patient and correlated with outcome at 6 months post injury. FINDINGS: Association between Mx and Mxa was moderately strong (r(2) = 0.73). However, limit of 95% accordance between both indices was +/-0.32. Mxa was significantly greater than Mx (0.22 +/- 0.22 versus 0.062 +/- 0.28; p < 0.000001). The difference between Mx and Mxa decreased with impairment of autoregulation (r = -0.39; p < 0.000001). Mean value of Mx showed a significant difference between dichotomized outcome groups (better autoregulation in patients with favourable than unfavourable outcome), while Mxa did not. CONCLUSIONS: Although relatively similar in a large group of patients, the differences between these two methods of assessment of dynamic autoregulation may be considerable in individual cases. When ICP is monitored, CPP rather than ABP should be included in the calculation of the autoregulatory index.

When is the ideal time to operate on a patient with a fracture of the hip? : a review of the available literature.

Fractures of the hip are common, often occurring in frail elderly patients, but also in younger fit healthy patients following trauma. They have a significant associated mortality and major social and financial implications to patients and health care providers. Many guidelines are available for the management of these patients, mostly recommending early surgery for the best outcomes. As a result, healthcare authorities now put pressure on surgical teams to 'fast track' patients with a fracture of the hip, often misquoting the available literature, which in itself can be confusing and even conflicting. This paper has been written following an extensive review of the available literature. An attempt is made to clarify what is meant by early surgery (expeditious versus emergency), and we conclude with a personal view for the practical management of these patients of variable age, fitness and type of surgery performed within services that are often under considerable pressure of finance and available operating theatres and qualified staff. Cite this article: Bone Joint J 2016;98-B:1573-81.

Total hip arthroplasty following failure of core decompression and tantalum rod implantation.

AIMS: One method of femoral head preservation following avascular necrosis (AVN) is core decompression and insertion of a tantalum rod. However, there may be a high failure rate associated with this procedure. The purpose of this study was to document the clinical and radiological outcomes following total hip arthroplasty (THA) subsequent to failed tantalum rod insertion. PATIENTS AND METHODS: A total of 37 failed tantalum rods requiring total hip arthroplasty were identified from a prospective database. There were 21 hips in 21 patients (12 men and nine women, mean age 37 years, 18 to 53) meeting minimum two year clinical and radiographic follow-up whose THAs were carried out between November 2002 and April 2013 (mean time between tantalum rod implantation and conversion to a THA was 26 months, 6 to 72). These were matched by age and gender to individuals (12 men, nine women, mean age 40 years, 18 to 58) receiving THA for AVN without prior tantalum rod insertion. RESULTS: There were no functional outcome differences between the two groups. Tantalum residue was identified on all post-operative radiographs in the tantalum group. Linear wear rates were comparable between groups with no evidence of catastrophic wear in either group. CONCLUSION: In the short term, tantalum rod implantation does not demonstrate an adverse effect on subsequent total joint replacement surgery. There is however, a high rate of retained tantalum debris on post-operative radiographs and thus there is an unknown risk of accelerated articular wear necessitating longer term study. Cite this article: Bone Joint J 2016;98-B:1175-9.

A review of the current management of severe traumatic brain injury.

Traumatic brain injury accounts for up to half of trauma related fatalities. This review describes current management practices including pre-hospital care, surgical interventions and various treatment modalities for intracranial hypertension. The lack of class I evidence for the majority of interventions is highlighted.

Identification of a novel receptor tyrosine kinase expressed in acute myeloid leukemic blasts.

Using the polymerase chain reaction with degenerate oligonucleotides derived from conserved motifs within the catalytic kinase domain of protein tyrosine kinases, and RNA extracted from embryonic stem cells, sequences that encode a segment of the kinase domain of several potentially novel receptor tyrosine kinases (RTKs) have been identified. One of these was selected for further study because in Northern analysis it hybridized to RNA from multipotential hematopoietic cell lines, but not from lines representative of lineage-committed cells. A cDNA for this receptor, designated developmental tyrosine kinase (DTK), was isolated and encodes a protein with structural similarities to AXL. Together these receptors form a new class of RTK. DTK is expressed in a number of human leukemic cell lines, and in the blasts of 6 of 11 patients with acute myeloid leukemia (AML) analyzed. The structure of DTK suggests that it may function as a cell adhesion molecule, and mediate cell-to-cell or cell-matrix interactions between hematopoietic cells and their respective microenvironments.

Analysis of false-positive borderline diagnoses in a glaucoma detection program.

Various glaucoma tests were given to 465 patients from the Department of Ophthalmology, University of Tennessee College of Medicine. An average of approximately 1.5 false-positive tests was found in each of 122 borderline cases that were proved not to have glaucoma after a continuous follow-up of from three months to three years. The significance of these false-positive tests was pointed out; explanations were given for them; recommendations were offered for their reduction.

Measurement technology applications in performance appraisal.

Every nursing administrator needs a credible performance appraisal system. By using psychometric methods and computer technology, the process of developing such a system can be more efficient and demonstrably successful. This article raises issues that relate to changing the performance appraisal system and gives a clear, step-by-step description of how computerized, statistical procedures were applied in improving nursing performance appraisal.

Wet cement remains a poorly recognised cause of full-thickness skin burns.

In 1993 we published a paper stating that wet construction cement is a poorly recognised cause of full-thickness burns [Injury 24 (1993) 615]. Ten years since publication we re-evaluated cement burns to ascertain if there had been any changes in awareness and incidence. All cement related burns assessed at this unit were reviewed over a three and a half year period. Postal questionnaires were sent to all those affected. Cement burns accounted for 2.2% of referrals to the Burns Unit during this studied period as compared to 1% during the original study. Fifty-one percent of patients stated they were unaware of the risk of cement burns and took no precautions. Eighty-six percent of the burns involved the lower limb. Fifty-three percent of burns affected professional users. Fifty percent had full-thickness involvement with 21% requiring operation. Eighty-eight percent of patients did not notice any warnings on the cement bag or delivery docket and 95% felt warnings should be larger and more obvious. This study has shown that cement burns may have resulted from shortcomings in the information and warnings provided to customers by cement manufacturers.

Analysis of the murine Dtk gene identifies conservation of genomic structure within a new receptor tyrosine kinase subfamily.

The receptor tyrosine kinase Dtk/Tyro 3/Sky/rse/brt/tif is a member of a new subfamily of receptors that also includes Axl/Ufo/Ark and Eyk/Mer. These receptors are characterized by the presence of two immunoglobulin-like loops and two fibronectin type III repeats in their extracellular domains. The structure of the murine Dtk gene has been determined. The gene consists of 21 exons that are distributed over 21 kb of genomic DNA. An isoform of Dtk is generated by differential splicing of exons from the 5' region of the gene. The overall genomic structure of Dtk is virtually identical to that determined for the human UFO gene. This particular genomic organization is likely to have been duplicated and closely maintained throughout evolution.

Isolation of a receptor tyrosine kinase (DTK) from embryonic stem cells: structure, genetic mapping and analysis of expression.

Analysis of receptor tyrosine kinases expressed during mouse embryonic stem cell differentiation resulted in the cloning of a receptor designated developmental tyrosine kinase (DTK). The 850 amino acid mature receptor protein comprises an extracellular domain with two immunoglobulin-like motifs and two fibronectin type III modules, a 25 amino acid transmembrane domain and a cytoplasmic region with a catalytic kinase domain. In embryonic stem cells growing in the presence of leukemia inhibitory factor DTK is abundantly expressed and this level of expression is maintained in differentiating embryonic stem cells and cystic embryoid bodies. In mid-gestational embryos (E14.5), DTK RNA is expressed in many tissues including brain, eye, thymus, lung, heart, gut, liver, testis and limbs. In contrast, expression of DTK in adult mice becomes restricted to brain, portions of the gastrointestinal tract, bladder, testis and ovary. There is enrichment of transcripts encoding DTK in purified fetal liver hematopoietic stem cells, when compared with unfractionated fetal liver. The DTK gene maps to mouse chromosome 2, band F.