Meniscal Transplant surgery or Optimised Rehabilitation full randomised trial (MeTeOR2): a study protocol.

INTRODUCTION: Pain and disability after meniscectomy can be a substantial lifelong problem. There are few treatment options, especially for young people. Non-surgical management (rehabilitation) is an option but increasingly surgeons are performing meniscal allograft transplants (MATs) for these individuals. However, this is still an uncommon procedure, and availability and usage of MAT vary widely both in the UK and internationally. It is not known which treatment option is the most effective and cost-effective. METHODS AND ANALYSIS: The Meniscal Transplant surgery or Optimised Rehabilitation trial is an international, multicentre, randomised controlled trial. The aim is to compare the clinical and cost effectiveness of MAT versus an optimised package of individualised, progressive, rehabilitation that we have called personalised knee therapy (PKT).Participants will be recruited from sites across the UK, Australia, Canada and Belgium. The planned 144 participants provide at least 90% power to detect a 10-point difference in the Knee injury and Osteoarthritis Outcome Score (KOOS4) at 24-months post randomisation (primary outcome). A prospectively planned economic evaluation will be conducted from a healthcare system and personal social services perspective. Secondary outcome data including health utility, occupational status, sports participation, mental well-being, further treatment, and adverse events will be collected at 3, 6, 12, 18, and 24 months. Analysis will be on an intention-to-treat basis and reported in-line with the Consolidated Standards of Reporting Trials statement. ETHICS AND DISSEMINATION: The trial was approved by the London-Bloomsbury Research Ethics Committee on 19 August 2022 (22/LO/0327) and Northern Sydney Local Health District Human Research Ethics Committee, NSW, Australia on the 13 March 2023 (2022/ETH01890).Trial results will be disseminated via peer-reviewed publications, presentations at international conferences, in lay summaries and using social media as appropriate.This protocol adheres to the recommended Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) checklist. TRIAL REGISTRATION NUMBER: ISRCTN87336549.

A prospective observational study of the effects of sugammadex on peri-operative oestrogen and progesterone levels in women who take hormonal contraception.

Pharmacokinetic modelling suggests that sugammadex may interact with endogenous progesterone and reduce levels by 34% in patients taking hormonal contraception. Due to this potential interaction that may be equivalent to missing one dose of an oral contraceptive pill, both the manufacturer and professional anaesthesia organisations recommend counselling patients to use additional non-hormonal contraception after administration of sugammadex. We performed a prospective observational study examining the changes in serum oestrogen and progesterone concentrations in premenopausal adult women undergoing an operative procedure. Sixty participants who were on hormonal contraception received sugammadex. Two additional control groups were recruited, consisting of 30 participants who were not on hormonal contraception and did not receive sugammadex, and 32 who were not on hormonal contraception and did receive sugammadex. Three blood samples were taken: before sugammadex; 15 min post-sugammadex; and 240 min post-sugammadex or end of operating theatre time. Median oestrogen levels decreased from baseline by around 40% at 240 min in all three groups (p ≤ 0.001). Progesterone levels rose significantly at 15 min (p = 0.002) in patients on contraception then decreased non-significantly to 20% below baseline at 240 min. The decrease in oestrogen and the rise in progesterone could both act to minimise the risk of ovulation and thus protect contraception in this population. We found no evidence of a change in hormone levels that might threaten contraceptive efficacy in women on hormonal contraception receiving sugammadex.

Unilateral diaphragmatic paresis following supracostal post-percutaneous nephrolithotomy.

Unilateral acquired diaphragmatic paresis is a known complication of thoracic surgeries. Direct mechanical injury to the phrenic nerve during surgery results in this complication. However its occurrence post-percutaneous nephrolithotomy (PCNL) has not been described. We report a 43-year-old man who underwent prone PCNL for endourological management of left complete staghorn calculus. Access via the 10th left intercostal space, under fluoroscopy, was carried out to remove the calculus. Post-operative, the routine chest radiograph revealed left hemidiaphragmatic blunting. Computerized tomography of the chest confirmed left hemidiaphragmatic elevation, suggesting unilateral diaphragmatic paresis. He did not have any respiratory symptoms, was managed conservatively with chest physiotherapy and incentive spirometry and responded extremely well. The absence of reported cases of diaphragmatic paresis post PCNL lends to a dearth in knowledge regarding recognition and management. This case report aims to acquaint urologists with this rare complication associated with supracostal PCNL and provide a rational management plan.

Is it safe to perform elective orthopaedic surgery with high community rates of COVID-19? An observational cohort study.

INTRODUCTION: During the first wave of the COVID-19 pandemic, University Hospitals Birmingham NHS Foundation trust was able to recommence elective orthopaedic surgery using private hospitals procured by the NHS as COVID-19 free 'green' sites. We report on the safety of elective orthopaedic surgery with high rates of community transmission. METHODS: We conducted an observational cohort study on consecutive NHS patients attending three private hospitals between 4 May 2020 and 16 June 2020. Patients attended preoperative assessment, including coronavirus disease (COVID-19) symptom screening, were instructed to self-isolate for 14 days and had a negative COVID-19 swab within 72 hours of surgery. Patient age, American Society of Anesthesiologists (ASA) grade, body mass index, surgery performed, type of anaesthetic and length of stay were collected. Our primary outcome was a positive COVID-19 swab, secondary outcomes were COVID-19 symptoms, readmission, surgical complications and mortality. RESULTS: Between 4 May 2020 and 16 June 2020, 191 patients were admitted to three private hospitals for elective surgery; 121 (67%) patients underwent general or regional anaesthetic, 179 patients were ASA grades 1 or 2 (94%) and 12 (6%) were ASA 3. In total, 187 (98%) patients were successfully contacted at 30 days postoperative and no COVID-19 symptoms, positive COVID-19 swabs or mortality or were recorded. One patient was readmitted following a pulmonary embolism and two patients were treated as outpatients for a deep vein thrombosis and a superficial infection. CONCLUSION: With 'green pathways' elective orthopaedic surgery can safely be performed while rates of COVID-19 in the community are high.

The use of triclosan-coated sutures to prevent surgical site infections: a systematic review and meta-analysis of the literature.

INTRODUCTION AND OBJECTIVES: Surgical site infections (SSIs) represent a common and serious complication of all surgical interventions. Microorganisms are able to colonise sutures that are implanted in the skin, which is a causative factor of SSIs. Triclosan-coated sutures are antibacterial sutures aimed at reducing SSIs. Our objective is to update the existing literature by systematically reviewing available evidence to assess the effectiveness of triclosan-coated sutures in the prevention of SSIs. METHODS: A systematic review of EMBASE, MEDLINE, AMED (Allied and complementary medicine database) and CENTRAL was performed to identify full text randomised controlled trials (RCTs) on 31 May 2019. INTERVENTION: Triclosan-coated sutures versus non-triclosan-coated sutures. PRIMARY OUTCOME: Our primary outcome was the development of SSIs at 30 days postoperatively. A meta-analysis was performed using a fixed-effects model. RESULTS: Twenty-five RCTs were included involving 11 957 participants. Triclosan-coated sutures were used in 6008 participants and non triclosan-coated sutures were used in 5949. Triclosan-coated sutures significantly reduced the risk of SSIs at 30 days (relative risk 0.73, 95% CI 0.65 to 0.82). Further sensitivity analysis demonstrated that triclosan-coated sutures significantly reduced the risk of SSIs in both clean and contaminated surgery. CONCLUSION: Triclosan-coated sutures have been shown to significantly reduced the risk of SSIs when compared with standard sutures. This is in agreement with previous work in this area. This study represented the largest review to date in this area. This moderate quality evidence recommends the use of triclosan-coated sutures in order to reduce the risk of SSIs particularly in clean and contaminated surgical procedures. PROSPERO REGISTRATION NUMBER: CRD42014014856.

Postoperative troponin measurement as a screening tool for adverse cardiac events in adult patients undergoing moderate or major non-cardiac surgery.

Elevated troponin levels within three days of surgery are strongly linked to major adverse cardiac events (MACE). However, the value of screening with troponin measurements is controversial. The extent to which this is done in routine practice is uncertain. We examined the medical records of all patients ≥45 years of age undergoing moderate or major non-cardiac surgery in our tertiary referral hospital over a six-month period. We determined how many patients had a troponin (TnT) measurement recorded in the first three days postoperatively, how many of these were abnormal, and the occurrence of MACE within 30 days. Two thousand and two hundred patients underwent 2,577 operations that met the study criteria. A postoperative TnT was measured after 4.5% of operations. Thirty-eight percent of patients with a recorded TnT measurement, and 44% of those with an abnormal measurement, experienced a MACE within 30 days. The sensitivity of an abnormal TnT to detect MACE was 86%. The specificity was low at 32% with a false positive rate of 56%. Patients with an abnormal TnT result had an increased risk of MACE (23%). The 'number needed to measure' to detect one patient with MACE was 4.4. In our institution, postoperative TnT levels were rarely measured and were used as a diagnostic rather than as a screening tool. The high false positive rate for MACE prediction limits its potential value as a screening tool. The test could be considered useful if it leads to further investigation, and may be best considered as one component of a multivariate approach to cardiac risk evaluation and diagnosis.

A new silicon tracker for proton imaging and dosimetry.

For many years, silicon micro-strip detectors have been successfully used as tracking detectors for particle and nuclear physics experiments. A new application of this technology is to the field of particle therapy where radiotherapy is carried out by use of charged particles such as protons or carbon ions. Such a treatment has been shown to have advantages over standard x-ray radiotherapy and as a result of this, many new centres offering particle therapy are currently under construction around the world today. The Proton Radiotherapy, Verification and Dosimetry Applications (PRaVDA) consortium are developing instrumentation for particle therapy based upon technology from high-energy physics. The characteristics of a new silicon micro-strip tracker for particle therapy will be presented. The array uses specifically designed, large area sensors with technology choices that follow closely those taken for the ATLAS experiment at the HL-LHC. These detectors will be arranged into four units each with three layers in an x-u-v configuration to be suitable for fast proton tracking with minimal ambiguities. The sensors will form a tracker capable of tracing the path of ~200 MeV protons entering and exiting a patient allowing a new mode of imaging known as proton computed tomography (pCT). This will aid the accurate delivery of treatment doses and in addition, the tracker will also be used to monitor the beam profile and total dose delivered during the high fluences used for treatment. We present here details of the design, construction and assembly of one of the four units that will make up the complete tracker along with its characterisation using radiation tests carried out using a 90Sr source in the laboratory and a 60 MeV proton beam at the Clatterbridge Cancer Centre.

Use of the Montreal Cognitive Assessment test to investigate the prevalence of mild cognitive impairment in the elderly elective surgical population.

Postoperative cognitive disorders are common in elderly patients. Pre-existing cognitive impairment including mild cognitive impairment may be an important risk factor for developing postoperative cognitive dysfunction and may not be detected in a standard preoperative interview, yet is not routinely sought. Our primary aim was to estimate the prevalence of mild cognitive impairment among elderly patients presenting to our hospital for elective surgery using a simple established screening tool: the Montreal Cognitive Assessment test. Secondarily, we wished to determine the proportion of patients with mild cognitive impairment who presented with this information available, the effect of increasing age on the prevalence of mild cognitive impairment and whether the timing and location of testing influenced results. We used the Montreal Cognitive Assessment test to screen preoperative patients aged 65 years and over. Our results suggested a potential prevalence of mild cognitive impairment of 56%, with prevalence increasing with age. No patients in the sample had a recorded diagnosis of mild cognitive impairment. Testing in either the preadmission clinic or on admission on the day of surgery yielded similar results. We found the Montreal Cognitive Assessment test to be a simple screening tool that was easily administered during the pre-admission visit.

Meniscal allograft transplantation: rationale for treatment.

The anatomy and microstructure of the menisci allow the effective distribution of load across the knee. Meniscectomy alters the biomechanical environment and is a potent risk factor for osteoarthritis. Despite a trend towards meniscus-preserving surgery, many tears are irreparable, and many repairs fail. Meniscal allograft transplantation has principally been carried out for pain in patients who have had a meniscectomy. Numerous case series have reported a significant improvement in patient-reported outcomes after surgery, but randomised controlled trials have not been undertaken. It is scientifically plausible that meniscal allograft transplantation is protective of cartilage, but this has not been established clinically to date.

Proton tracking for medical imaging and dosimetry.

For many years, silicon micro-strip detectors have been successfully used as tracking detectors for particle and nuclear physics experiments. A new application of this technology is to the field of particle therapy, where radiotherapy is carried out by use of charged particles such as protons or carbon ions. Such a treatment has been shown to have advantages over standard x-ray radiotherapy and as a result of this, many new centres offering particle therapy are currently under construction - including two in the U.K.. The characteristics of a new silicon micro-strip detector based system for this application will be presented. The array uses specifically designed large area sensors in several stations in an x-u-v co-ordinate configuration suitable for very fast proton tracking with minimal ambiguities. The sensors will form a tracker capable of giving information on the path of high energy protons entering and exiting a patient. This will allow proton computed tomography (pCT) to aid the accurate delivery of treatment dose with tuned beam profile and energy. The tracker will also be capable of proton counting and position measurement at the higher fluences and full range of energies used during treatment allowing monitoring of the beam profile and total dose. Results and initial characterisation of sensors will be presented along with details of the proposed readout electronics. Radiation tests and studies with different electronics at the Clatterbridge Cancer Centre and the higher energy proton therapy facility of iThemba LABS in South Africa will also be shown.

Enhanced education and physiotherapy before knee replacement; is it worth it? A systematic review.

BACKGROUND: Around 20% of knee replacement have an unsatisfactory outcome. Pre-operative physiotherapy and education have been proposed to improve post-operative outcomes. OBJECTIVES: This systematic review evaluated whether these factors improved length of stay and patient reported outcomes after knee replacement surgery. DATA SOURCES: Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, PsycINFO and PEDro were searched on the 1st January 2013. STUDY SELECTION OR ELIGIBILITY CRITERIA: Randomised or quasi-randomised studies assessing either pre-operative education or physiotherapy on patients undergoing a planned total or partial knee replacement were included in the review. Only studies with a control group receiving a defined standard of pre-operative care were included. RESULTS: Eleven studies met the inclusion criteria set. Two studies analysed the effect of pre-operative education, seven pre-operative treatment by a physiotherapist and two studies used both factors. No study found significant differences in validated joint specific patient reported outcome measures. The education studies found a decrease in pre-operative expectation and an improvement in knowledge, flexion and regularity of exercise. Two studies found an improvement in muscle strength in the group treated by a physiotherapist at three months. The combination of education and physiotherapy was shown to reduce patient length of stay and cost in one study. CONCLUSION: The evidence reviewed is insufficient to support the implementation of either pre-operative education or physiotherapy programmes. The combination of pre-operative education and treatment by a physiotherapist may reduce the medical costs associated with surgery.

Changing patterns in endotracheal intubation for anaesthesia trainees: a retrospective analysis of 80,000 cases over 10 years.

Several overseas studies have suggested that opportunities for anaesthesia trainees to learn and practise endotracheal intubation have decreased over time. We analysed the operating theatre data collection system at a large Australian metropolitan teaching hospital from 1998 to 2008 to determine if numbers for trainees' caseloads in general, and endotracheal intubation in particular had changed. The total caseload per trainee of approximately 800 cases per year was stable throughout the study period. The number of gastrointestinal endoscopies per trainee increased significantly with a corresponding decrease in the number of other cases. The mean number of endotracheal intubations per trainee per year fell by 10% and of supraglottic devices by 16%, neither of which was statistically significant. Endotracheal intubation for caesarean sections did however fall significantly from an average of nine to an average of six cases per trainee per year. Our findings contrast with other reports of much larger decreases in the number of endotracheal intubations performed by trainees over the last decade, but suggest that our local practice is similar to the international experience of decreasing opportunities for endotracheal intubation in obstetric anaesthesia.

Moderate and high intensity sprint exercise induce differential responses in COX4I2 and PDK4 gene expression in Thoroughbred horse skeletal muscle.

REASONS FOR PERFORMING STUDY: The role of molecular signalling pathways in the phenotypic adaptation of skeletal muscle to different exercise stimuli in the Thoroughbred horse has not been reported previously. OBJECTIVE: To examine CKM, COX4I1, COX4I2 and PDK4 gene expression following high intensity sprint and moderate intensity treadmill exercise stimuli in skeletal muscle of Thoroughbred horses. MATERIALS AND METHODS: Two groups of trained 3-year-old Thoroughbred horses participated. Group A (n = 6 females, n = 3 males) participated in an incremental step test (moderate intensity) to fatigue or HR(max) on a Sato high speed treadmill (distance = 5418.67 m ± 343.21). Group B (n = 8 females) participated in routine 'work' (sprint) on an all-weather gallop (distance = 812.83 m ± 12.53). Biopsy samples were obtained from the gluteus medius pre-exercise (T(0)), immediately post exercise (T(1)) and 4 h post exercise (T(2)). For physiological relevance venous blood samples were collected to measure plasma lactate and creatine kinase concentrations. Changes in mRNA expression were determined by quantitative real-time RT-PCR for creatine kinase muscle (CKM), cytochrome c oxidase subunit IV isoform 1 (COX4I1), cytochrome c oxidase subunit IV isoform 2 (COX4I2) and pyruvate dehydrogenase kinase, isozyme 4 (PDK4) genes. Statistical significance (α < 0.05) was determined using Student's t tests. RESULTS: COX4I2 mRNA expression decreased significantly in Group A and remained unchanged in Group B between T(0) vs. T(2) (-1.7-fold, P = 0.017; -1.0-fold, P = 0.859). PDK4 mRNA expression increased significantly in Group B but not in Group A between T(0) vs. T(1) (3.8-fold, P = 0.039; 1.4-fold, P = 0.591). There were no significant changes in the expression in CKM or COX4I1 mRNA abundance in either group. CONCLUSIONS: Different exercise protocols elicit variable transcriptional responses in key exercise relevant genes in equine skeletal muscle due to variation in metabolic demand.

Construct design for efficient, effective and high-throughput gene silencing in plants.

Post-transcriptional silencing of plant genes using anti-sense or co-suppression constructs usually results in only a modest proportion of silenced individuals. Recent work has demonstrated the potential for constructs encoding self-complementary 'hairpin' RNA (hpRNA) to efficiently silence genes. In this study we examine design rules for efficient gene silencing, in terms of both the proportion of independent transgenic plants showing silencing, and the degree of silencing. Using hpRNA constructs containing sense/anti-sense arms ranging from 98 to 853 nt gave efficient silencing in a wide range of plant species, and inclusion of an intron in these constructs had a consistently enhancing effect. Intron-containing constructs (ihpRNA) generally gave 90-100% of independent transgenic plants showing silencing. The degree of silencing with these constructs was much greater than that obtained using either co-suppression or anti-sense constructs. We have made a generic vector, pHANNIBAL, that allows a simple, single PCR product from a gene of interest to be easily converted into a highly effective ihpRNA silencing construct. We have also created a high-throughput vector, pHELLSGATE, that should facilitate the cloning of gene libraries or large numbers of defined genes, such as those in EST collections, using an in vitro recombinase system. This system may facilitate the large-scale determination and discovery of plant gene functions in the same way as RNAi is being used to examine gene function in Caenorhabditis elegans.

Replicating satellite RNA induces sequence-specific DNA methylation and truncated transcripts in plants.

Tobacco plants were transformed with a chimeric transgene comprising sequences encoding beta-glucuronidase (GUS) and the satellite RNA (satRNA) of cereal yellow dwarf luteovirus. When transgenic plants were infected with potato leafroll luteovirus (PLRV), which replicated the transgene-derived satRNA to a high level, the satellite sequence of the GUS:Sat transgene became densely methylated. Within the satellite region, all 86 cytosines in the upper strand and 73 of the 75 cytosines in the lower strand were either partially or fully methylated. In contrast, very low levels of DNA methylation were detected in the satellite sequence of the transgene in uninfected plants and in the flanking nonsatellite sequences in both infected and uninfected plants. Substantial amounts of truncated GUS:Sat RNA accumulated in the satRNA-replicating plants, and most of the molecules terminated at nucleotides within the first 60 bp of the satellite sequence. Whereas this RNA truncation was associated with high levels of satRNA replication, it appeared to be independent of the levels of DNA methylation in the satellite sequence, suggesting that it is not caused by methylation. All the sequenced GUS:Sat DNA molecules were hypermethylated in plants with replicating satRNA despite the phloem restriction of the helper PLRV. Also, small, sense and antisense approximately 22 nt RNAs, derived from the satRNA, were associated with the replicating satellite. These results suggest that the sequence-specific DNA methylation spread into cells in which no satRNA replication occurred and that this was mediated by the spread of unamplified satRNA and/or its associated 22 nt RNA molecules.

Anticoagulant-induced pseudothrombocytopenia in a patient presenting for coronary artery bypass grafting.

A 73-yr-old man with severe ischaemic heart disease presented for coronary artery bypass grafting. His preoperative platelet count, obtained from an ethylene diamine tetraacetic acid (EDTA) sampling bottle, was 61 x 10(9) litre-1, but he had no history of bleeding problems. Previous platelet counts demonstrated results ranging from 16 x 10(9) litre-1 to 254 x 10(9) litre-1 with variable degrees of in vitro platelet clumping. Preoperative thrombelastography reflected a normal coagulation profile. The laboratory findings and the absence of a history of haemorrhagic complications suggested a diagnosis of EDTA-dependent pseudothrombocytopenia. We present the perioperative implications of this in vitro phenomenon and methods of detecting the functional and numerical integrity of circulating platelets.

Evidence for horizontal and not vertical transmission of human herpesvirus 8 in children born to human immunodeficiency virus-infected mothers.

A survey of antibody responses to human herpesvirus 8 (HHV-8) was undertaken to examine the mode of transmission of this virus to children born to mothers with HIV. Methods. Serum samples from a cohort of 92 mother-infant pairs and a cross-sectional cohort of 100 children (median age, 4 years) were tested. In the cohort of mother-infant pairs, 14 infants were HIV-infected, 72 were not and the HIV status was unknown for 6. In the cohort of children 70 were HIV-infected and 30 were vertically exposed but uninfected. Serologic responses to two HHV-8 antigens, latency-associated nuclear antigen and the structural antigen encoded by open reading frame 65 were detected by immunofluorescent antibody test and enzyme-linked immunoassay. Results were confirmed by Western blot. Results. All HHV-8-seropositive mothers were African (17 of 92, 18.5%). Six of their infants were HHV-8-seronegative and 11 had at least 1 HHV-8-seropositive sample. One of the 11 infants tested only at birth had a lower antibody titer than the mother; the remaining 10 infants had decreasing titers up to 7 months of age and 6 became seronegative. No infants born to HHV-8-seronegative mothers had antibodies to the virus. The seroprevalence to HHV-8 was 6% in the cohort of children. All had African mothers and their median age was greater than that of the cohort (8.4 vs. 4.0 years). Five were coinfected with HIV. Conclusions. HHV-8 was not vertically transmitted by any of the HIV-coinfected mothers. Acquisition of antibody to HHV-8 occurred in older children, implying a horizontal route of transmission.

Serologic evidence of human herpesvirus 8 transmission by homosexual but not heterosexual sex.

Epidemiologic studies link Kaposi's sarcoma with a sexually transmitted agent. Human herpesvirus 8 (HHV-8) is likely to be that agent, but routes of transmission are poorly described. A seroepidemiologic study was conducted to determine whether HHV-8 is transmitted sexually between heterosexuals. Sera from 2718 patients attending a sexually transmitted disease (STD) clinic were tested for antibodies to HHV-8 and herpes simplex virus type 2 (HSV-2). Information on sex partners in the previous 12 months and past STDs were obtained by questionnaire. Relationships between possible risk factors and HHV-8 infection were assessed by logistic regression. Overall, seroprevalence of HHV-8 was 7.3%. Independent risk factors for HHV-8 in the whole group were homo/bisexuality and birth in Africa and, among homo/bisexual men, a history of syphilis and HSV-2 and human immunodeficiency virus seropositivity. Among heterosexuals there was no evidence for sexual transmission; the only independent risk factor for HHV-8 seropositivity was birth in Africa.