Impact of intravenous tranexamic acid on patients undergoing shoulder arthroplasty surgery.

Background: Shoulder arthroplasty surgery carries the risk of blood loss. The antifibrinolytic tranexamic acid (TXA) is effective in reducing blood loss in lower limb arthroplasty. The purpose of this study was to assess blood loss and associated complications following shoulder arthroplasty performed with and without TXA for both elective and trauma indications. Methods: A cohort study was performed to assess blood loss, transfusion requirements and post-operative venous thromboembolic events (VTE) following shoulder arthroplasty undertaken with and without the use of intravenous TXA. Results: The study consisted of 67 patients (n = 36 with TXA; n = 31 without TXA). Type of arthroplasty included reverse-shoulder arthroplasty, total-shoulder arthroplasty and hemiarthroplasty. There was no significant difference between TXA and non-TXA groups regarding blood loss (TXA group haemoglobin drop 20.6 mg/dL; non-TXA group haemoglobin drop 20.5 mg/dL; p = 0.978). There was no significant difference in measured outcomes with or without TXA use for elective or trauma indications, nor regarding type of arthroplasty. Discussion: The use of intravenous TXA in shoulder arthroplasty was not associated with a significant reduction in blood loss or post-operative transfusion rates, nor did it impact on VTE. This result was not affected by the indication being elective or trauma nor the type of arthroplasty surgery performed.

Review: Challenges in the histopathological classification of ganglioglioma and DNT: microscopic agreement studies and a preliminary genotype-phenotype analysis.

Low-grade epilepsy-associated brain tumours (LEAT) are the second most common cause for drug-resistant, focal epilepsy, that is ganglioglioma (GG) and dysembryoplastic neuroepithelial tumours (DNT). However, molecular pathogenesis, risk factors for malignant progression and their frequent association with drug-resistant focal seizures remain poorly understood. This contrasts recent progress in understanding the molecular-genetic basis and targeted treatment options in diffuse gliomas. The Neuropathology Task Force of the International League Against Epilepsy examined available literature to identify common obstacles in diagnosis and research of LEAT. Analysis of 10 published tumour series from epilepsy surgery pointed to poor inter-rater agreement for the histopathology diagnosis. The Task Force tested this hypothesis using a web-based microscopy agreement study. In a series of 30 LEAT, 25 raters from 18 countries agreed in only 40% of cases. Highest discordance in microscopic diagnosis occurred between GG and DNT variants, when oligodendroglial-like cell patterns prevail, or ganglion cells were difficult to discriminate from pre-existing neurons. Suggesting new terminology or major histopathological criteria did not satisfactorily increase the yield of histopathology agreement in four consecutive trials. To this end, the Task Force applied the WHO 2016 strategy of integrating phenotype analysis with molecular-genetic data obtained from panel sequencing and 450k methylation arrays. This strategy was helpful to distinguish DNT from GG variants in all cases. The Task Force recommends, therefore, to further develop diagnostic panels for the integration of phenotype-genotype analysis in order to reliably classify the spectrum of LEAT, carefully characterize clinically meaningful entities and make better use of published literature.

Improving the safety and tolerability of local anaesthetic outpatient transperineal prostate biopsies: A pilot study of the CAMbridge PROstate Biopsy (CAMPROBE) method.

OBJECTIVES: The aim of this study was to pilot the use of a bespoke device (CAMPROBE, the CAMbridge PROstate Biopsy) to enable routine outpatient free-hand local anaesthetic (LA) transperineal prostate biopsies. MATERIALS AND METHODS: The CAMPROBE prototype was designed and built in our institution. Men on active surveillance due prostate resampling were invited to have a CAMPROBE biopsy as an alternative to repeat transrectal ultrasound-guided prostate biopsies (TRUSBx) as part of an approved trial (NCT02375035). Biopsies were performed using LA infiltration only, without sedation or additional analgesia. Patient-reported outcomes were recorded at day 0 and 7 using validated questionnaires and visual analogue scales (VAS). Complications were recorded prospectively. RESULTS: Thirty men underwent biopsies with a median of 11 cores taken per procedure (interquartile range 10-12). There were no infections, sepsis or retention episodes. Haematuria and haematospermia occurred in 67% and 62% of patients, which are similar to rates reported for TRUSBx. Mean VAS for pain (0-10 scale) was less than 3 for every part of the procedure. All 30 men described the procedure as tolerable under LA. In total, 26/30 (86.7%) men expressed a preference for a CAMPROBE procedure over TRUSBx and a further 3 (10.0%) would have either. CONCLUSIONS: In this small pilot study, the CAMPROBE device and method appears to be a safe, simple and well-tolerated out-patient transperineal replacement for TRUSBx. A major new National Institute for Health Research grant will allow its further development from a prototype to a single use, low-cost disposable device ready for multi-centre testing. LEVEL OF EVIDENCE: 1b: individual cohort study.

Review: Molecular characteristics of long-term epilepsy-associated tumours (LEATs) and mechanisms for tumour-related epilepsy (TRE).

Brain tumours are the second most common cause of seizures identified in epilepsy surgical series. While any tumour involving the brain has the potential to cause seizures, specific subtypes are more frequently associated with epilepsy. Tumour-related epilepsy (TRE) has a profound impact on patients with brain tumours and these seizures are often refractory to anti-epileptic treatments, resulting in long-term disability and patient morbidity. Despite the drastic impact of epilepsy-associated tumours on patients, they have not traditionally enjoyed as much attention as more malignant neoplasms. However, recently a number of developments have been achieved towards further understanding of the molecular and developmental backgrounds of specific epilepsy-associated tumours. In addition, the past decade has seen an expansion in the literature on the pathophysiology of TRE. In this review, we aim to summarize the mechanisms by which tumours may cause seizures and detail recent data regarding the pathogenesis of specific developmental epilepsy-associated tumours.

Sex differences in the splenic flexure.

INTRODUCTION Anecdotally, surgeons claim splenic flexure mobilisation is more difficult in male patients. There have been no scientific studies to confirm or disprove this hypothesis. The implications in colorectal surgery could be profound. The aim of this study was to assess quantitatively whether there is an anatomical difference in the position of the splenic flexure between men and women using computed tomography (CT). METHODS Portal venous phase CT performed for preoperative assessment of colorectal malignancy was analysed using the hospital picture archiving and communication system. The splenic flexure was compared between men and women using two variables: anatomical height corresponding to the adjacent vertebral level (converted to ordinal values between 1 and 17) and distance from the midline. RESULTS In total, 100 CT images were analysed. Sex distribution was even. The mean ages of the male and female patients were 68.1 years and 66.7 years respectively (p=0.630). The mean vertebral level for men was 8.88, equating to the inferior half of the T11 vertebral body (range: 1-17 [superior half of T9 to inferior half of L2]), and 11.36 for women, equating to the inferior half of the T12 vertebral body (range: 4-16 [superior half of T10 to superior half of L2]). This difference was statistically significant (p=0.0001) and is equivalent to one whole vertebra. The mean distance from the midline was 160.8mm (range: 124-203mm) for men and 138.2mm (range: 107-185mm) for women (p<0.0001). CONCLUSIONS The splenic flexure is both higher and further from the midline in men than in women. This provides one theory as to why mobilising the splenic flexure may be more difficult in male patients.

Anatomical siting of the splenic flexure using computed tomography.

INTRODUCTION Often, left-sided colorectal surgery requires splenic flexure mobilisation (SFM) to allow a tension-free anastomosis to be carried out. This step is difficult and not without risk. We investigated a system of anatomical siting of the splenic flexure using computed tomography (CT). METHODS The Shrewsbury Splenic Flexure Siting (SSFS) system involves siting of the splenic flexure using the vertebral level (VL) as a reference point. We asked three surgical registrars (SRs) to analyse 20 CT scans of patients undergoing colonic resection to ascertain the anatomical site of the splenic flexure using the SSFS system. The distance from the centre of the vertebral body to the lateral edge (CVBL) of the splenic flexure was measured, as was the distance from the centre of the vertebral body to the inner abdominal wall (CVBI) along the same line, on axial images. RESULTS VL assessment demonstrated substantial inter-observer agreement with a kappa (κ) value of 0.742 (95% confidence interval (CI), 0.463-0.890). CVBL and CVBI demonstrated very strong inter-observer agreement (CVBL: κ = 0.905 (95% CI, 0.785-0.961); CVBI: 0.951 (0.890-0.979) (p<0.001). Overall, there was strong correlation between assessments by all three SRs across the three variables measured. CONCLUSIONS The SSFS system is an accurate method to site the splenic flexure anatomically using CT. We can use the SSFS system to develop a validated scoring system to help colorectal surgeons assess the difficulty of SFM.

Robotic surgery in trauma and orthopaedics: a systematic review.

The use of robots in orthopaedic surgery is an emerging field that is gaining momentum. It has the potential for significant improvements in surgical planning, accuracy of component implantation and patient safety. Advocates of robot-assisted systems describe better patient outcomes through improved pre-operative planning and enhanced execution of surgery. However, costs, limited availability, a lack of evidence regarding the efficiency and safety of such systems and an absence of long-term high-impact studies have restricted the widespread implementation of these systems. We have reviewed the literature on the efficacy, safety and current understanding of the use of robotics in orthopaedics.

Involvement of the proteasome and caspase activation in hippocampal long-term depression induced by the serine protease subtilisin.

The serine protease subtilisin-A produces a long-term depression (LTD) of synaptic potentials in hippocampal slices which differs mechanistically from classical LTD. Since caspases have been implicated in hippocampal plasticity, this study examined a possible role for these enzymes in subtilisin-induced LTD. Subtilisin produced a concentration-dependent decrease in the size of field excitatory synaptic potentials (fEPSPs), which was not prevented or modified by the caspase inhibitors Z-VAD(OMe)-fmk and Z-DEVD-fmk. Similarly Z-VAD(OMe)-fmk did not modify the selective loss of protein expression produced by subtilisin. Subtilisin reduced the expression of procaspase-3 and caspase-9 but, while caspase-9 was converted to its conventionally activated form (39 kDa), caspase-3 was metabolised along a non-canonical pathway to a 29/30 kDa protein rather than the classical 17/19 kDa fragments. Both Z-VAD(OMe)-fmk and Z-DEVD-fmk were unable to prevent the reduced expression of Postsynaptic Density Protein-95, Vesicle-Associated Membrane Protein-1 and Unco-ordinated 5H3 proteins produced by subtilisin, although MG132 did produce partial recovery from subtilisin-induced depression of fEPSPs. When tested on long-term potentiation (LTP) induced by theta stimulation in the stratum radiatum, MG132 inhibited the immediate increase in fEPSP size but generated a higher plateau LTP. Twin LTP stimulation generated a further increase in LTP amplitude in control slices but not in slices exposed to MG132. The results indicate that subtilisin does produce caspase activation but that this does not contribute to its induction of LTD. However, activation of the proteasome does contribute to subtilisin-induced LTD and may also play a modulatory role in electrically induced LTP.

Audit of trauma case load suitable for a day surgery trauma list and cost analysis.

BACKGROUND: Day surgery trauma lists are becoming an increasingly popular and widespread approach to address the inpatient trauma demand on NHS services. A 'Rapid Access' list initiative was set-up to book patients from an emergency pathway who require surgery and also fulfilled the standard day case patient criteria but for whom it was safe to wait for over 24 h before going to theatre. MATERIALS & METHODS: We performed a prospective audit of the cases undertaken on the day surgery trauma list over a 12-month period and analysed the number of cases, spectrum of procedures, complications and the cost benefits. RESULTS: A total of 119 day surgery trauma cases were performed (42 lists; average of 3 cases per list; upper limb procedures accounted for 60%.). The overall cost benefit for day surgery was calculated as the difference between the tariff and the costs for day surgery and inpatient procedures. A cost benefit of £617 per case for day surgery over inpatient surgery was noted with a total saving of £67,450 for the performed procedures. DISCUSSION: We demonstrate day trauma surgery to be a safe and cost effective method of optimising the management of the appropriate trauma case workload. Further it reduces demand for inpatient beds, provides significant cost savings for the trust and improves patient satisfaction.

Outcome analysis of trapezectomy with and without pyrocarbon interposition to treat primary arthrosis of the trapeziometacarpal joint.

We performed a prospective cohort comparative analysis of simple trapezectomy and trapezectomy with pyrocarbon interposition in 38 consecutive patients with trapeziometacarpal joint osteoarthrosis. Patients were assessed preoperatively, at six and 12 months postoperatively using subjective and objective tools. Subjective assessment was performed using the Quick Disabilities of the Arm, Shoulder, and Hand questionnaire and the visual analogue score. Objective assessment was performed with grip strength measurements. At each time interval, statistical differences were sought between the two subgroups. No significant difference between the two subgroups was noted at any time interval on subjective or objective assessment. A significant difference (p < 0.05) was found on comparing the respective preoperative and 12-month subjective scores in both subgroups. Of the pyrocarbon subgroup seven had related complications. We suggest that pyrocarbon interposition does not significantly improve postoperative function, requires a longer operation with a high postoperative risk of pyrocarbon displacement and need for revision surgery.

Classification of the morphology of the acromioclavicular joint using cadaveric and radiological analysis.

The aim of this study was to establish a classification system for the acromioclavicular joint using cadaveric dissection and radiological analyses of both reformatted computed tomographic scans and conventional radiographs centred on the joint. This classification should be useful for planning arthroscopic procedures or introducing a needle and in prospective studies of biomechanical stresses across the joint which may be associated with the development of joint pathology. We have demonstrated three main three-dimensional morphological groups namely flat, oblique and curved, on both cadaveric examination and radiological assessment. These groups were recognised in both the coronal and axial planes and were independent of age.

Outcome analysis of surgery for disorders of the rotator cuff: a comparison of subjective and objective scoring tools.

A consecutive series of 372 patients who underwent surgery for disorders of the rotator cuff involving arthroscopic subacromial decompression and open or arthroscopic repairs of the cuff were prospectively investigated as to the comparability of subjective and objective assessment scores of shoulder function. Assessments were made before operation and at 3, 6, 12, 18 and 24 months after surgery using the Disabilities of the Arm, Shoulder, and Hand score, the Oxford shoulder score and the Constant-Murley score, which was used as a reference. All scores were standardised to a scale of 0 to 100 for comparison. Statistical analysis compared the post-operative course and the mean score for the subjective Disabilities to the Arm, Shoulder and Hand score and Oxford shoulder score, with the objective Constant score at each interval. A strong correlation was evident between both subjective scores and the Constant score. We concluded that both the subjective scores would be useful substitutes for the Constant score, obviating the need for a trained investigator and the specialist equipment required to perform the Constant score.

Gender-specific Constant score correction for age.

To investigate the relationship between age, gender and the Constant score. Two hundred and seventy Healthy volunteers (527 normal shoulders) from our local population with no previous history of shoulder disease were assessed using the Constant score. The mean age was 43.9 years (16-86) and the mean Constant score 85.9 (56-100). The mean score was 88.1 (range 56-100) for men and 83.7 (range 60-100) for women. A mixed regression model estimated that, for the male population, the Constant score falls by 0.15 points per annum between the ages of 50 and 70 and by 1.3 points per year after the age of 70. Similarly, for the female population, the fall is of 0.25 per year between 60 and 70 and 0.35 after the age of 70. The changes are statistically significant (P < 0.01) and clinically important when comparing patients of different age groups.

An analysis of outcome of arthroscopic versus mini-open rotator cuff repair using subjective and objective scoring tools.

The purpose is to perform a comparative analysis of mini-open and arthroscopic rotator cuff repairs through the use of subjective and objective scoring tools. We conducted a prospective comparative cohort study that evaluated 123 consecutive patients who underwent rotator cuff repairs (arthroscopic and 31 mini-open repair). Subjective and objective functional assessment was performed preoperatively and postoperatively at 3, 6, 12, 18 and 24 months using the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, the Oxford Shoulder Score (OSS) and the Constant-Murley score. Statistical analysis was performed on the datasets assessing the Pearson correlation coefficients and any significant differences present at each respective time point. At every time point the arthroscopic group scored better than the mini-open group, regardless of the assessment tool employed. The percentage recovery from the baseline measured at 1 year was similar with either treatment option. A significant difference was found between the arthroscopic and mini-open groups for the Constant-Murley, DASH and OSS scoring systems preoperatively (P < 0.05), reflecting a difference in tear severity. Arthroscopic rotator cuff repair is comparable with the mini-open technique with well correlated postoperative rates recovery. Subjective scoring provides an accurate and potentially easier method of postoperative assessment for long-term follow-up of rotator cuff repairs.

Combined endoscopic trans-anal rectal mucosal ablation and laparoscopic partial proctectomy for ulcerative colitis--a new procedure.

A case is reported in which endoscopic trans-anal rectal mucosal ablation (ETARMA) was employed in combination with laparoscopic partial proctectomy in order to decrease complications associated with open surgery.

Laparoscopic management of iatrogenic bladder injury and bladder stone formation following laparoscopic inguinal herniorrhaphy.

BACKGROUND: Herniorrhaphy is one of the most commonly performed operations in the UK. Approximately 1 per 1,000 of the population has a groin hernia. METHOD AND RESULT: We report on a rare complication following laparoscopic inguinal herniorrhaphy of bladder stone formation and its management. CONCLUSION: To our knowledge a combined laparoscopic repair of the urinary bladder wall, following iatrogenic injury by a mesh fixation clip and retrieval of bladder stone (induced through the misplacement of the clip) has not been described previously.

Tryptophan, adenosine, neurodegeneration and neuroprotection.

This review summarises the potential contributions of two groups of compounds to cerebral dysfunction and damage in metabolic disease. The kynurenines are oxidised metabolites of tryptophan, the kynurenine pathway being the major route for tryptophan catabolism in most tissues. The pathway includes quinolinic acid -- an agonist at N-methyl-D-aspartate (NMDA) receptors, kynurenic acid -- an antagonist at glutamate and nicotinic receptors, and other redox active compounds that are able to generate free radicals under many physiological and pathological conditions. The pathway is activated in immune-competent cells, including glia in the central nervous system, and may contribute substantially to delayed neuronal damage following an infarct or metabolic insult. Adenosine is an ubiquitous purine that can protect neurons by suppressing excitatory neurotransmitter release, reducing calcium fluxes and inhibiting NMDA receptors. The extent of brain injury is critically dependent on the balance between the two opposing forces of kynurenines and purines.

Purine metabolism and clinical status of patients with rheumatoid arthritis treated with dipyridamole.

The anti-inflammatory activities of methotrexate and sulphasalazine may be mediated by increases in endogenous adenosine levels. Since the vascular protective drug dipyridamole inhibits the uptake and metabolism of adenosine we have now tested this compound in patients with rheumatoid arthritis to assess its effects on their symptoms. Forty patients (aged 18-75 years) received dipyridamole 400 mg/day or placebo. The levels of adenosine and its major metabolites were determined by high performance liquid chromatography (HPLC) in blood samples taken at baseline and at monthly intervals during treatment for 6 months. After three months of treatment there was a significant reduction in the modified Health Assessment Questionnaire (mHAQ) score, but these effects were not maintained, and dipyridamole did not modify disease severity scores or the levels of adenosine and its metabolites. We conclude that the symptoms of rheumatoid arthritis were not modified by treatment with dipyridamole.

Modulation of cytokine release by purine receptors in patients with rheumatoid arthritis.

OBJECTIVE: Since adenosine receptors are known to modulate the release of some inflammatory mediators in control subjects, we have examined the effects of the mixed A1 and A2 adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA) on basal and lipopolysaccharide (LPS)-induced cytokine release in diluted whole blood cultures from rheumatoid arthritis (RA) patients and healthy volunteers. METHODS: Twenty-eight patients with rheumatoid arthritis aged 18-75 years gave their voluntary consent to participate and give a blood sample. Basal levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) were measured by ELISA, and whole blood cultures were prepared to assess the effects of LPS activation. RESULTS: Following a 40-hour incubation, activation of adenosine receptors by NECA, added to the cell cultures from rheumatoid arthritis patients, was found to suppress both the basal and LPS-induced release of TNF-alpha and IL-1beta, while causing an increase in the release of both basal and LPS-induced IL-6. In healthy volunteers basal cytokines were undetectable, but NECA alone induced the release of all three cytokines. Stimulated levels of TNF-alpha were more than double those in patients. In the control blood cultures, NECA suppressed LPS-induced release of TNF-alpha and IL-1beta, but increased IL-6 release. CONCLUSIONS: Adenosine receptor stimulation has a differential effect on the release of pro-inflammatory cytokines, and may induce cytokine release in normal subjects. Stimulated release of TNF-alpha is substantially lower in patients with rheumatoid arthritis than in control subjects, possibly indicating saturation, exhaustion or down-regulation of the release process.