Timing of elective surgery and risk assessment after SARS-CoV-2 infection: an update: A multidisciplinary consensus statement on behalf of the Association of Anaesthetists, Centre for Perioperative Care, Federation of Surgical Specialty Associations, Royal College of Anaesthetists, Royal College of Surgeons of England.

The impact of vaccination and new SARS-CoV-2 variants on peri-operative outcomes is unclear. We aimed to update previously published consensus recommendations on timing of elective surgery after SARS-CoV-2 infection to assist policymakers, administrative staff, clinicians and patients. The guidance remains that patients should avoid elective surgery within 7 weeks of infection, unless the benefits of doing so exceed the risk of waiting. We recommend individualised multidisciplinary risk assessment for patients requiring elective surgery within 7 weeks of SARS-CoV-2 infection. This should include baseline mortality risk calculation and assessment of risk modifiers (patient factors; SARS-CoV-2 infection; surgical factors). Asymptomatic SARS-CoV-2 infection with previous variants increased peri-operative mortality risk three-fold throughout the 6 weeks after infection, and assumptions that asymptomatic or mildly symptomatic omicron SARS-CoV-2 infection does not add risk are currently unfounded. Patients with persistent symptoms and those with moderate-to-severe COVID-19 may require a longer delay than 7 weeks. Elective surgery should not take place within 10 days of diagnosis of SARS-CoV-2 infection, predominantly because the patient may be infectious, which is a risk to surgical pathways, staff and other patients. We now emphasise that timing of surgery should include the assessment of baseline and increased risk, optimising vaccination and functional status, and shared decision-making. While these recommendations focus on the omicron variant and current evidence, the principles may also be of relevance to future variants. As further data emerge, these recommendations may be revised.

SARS-CoV-2 infection, COVID-19 and timing of elective surgery: A multidisciplinary consensus statement on behalf of the Association of Anaesthetists, the Centre for Peri-operative Care, the Federation of Surgical Specialty Associations, the Royal College of Anaesthetists and the Royal College of Surgeons of England.

The scale of the COVID-19 pandemic means that a significant number of patients who have previously been infected with SARS-CoV-2 will require surgery. Given the potential for multisystem involvement, timing of surgery needs to be carefully considered to plan for safe surgery. This consensus statement uses evidence from a systematic review and expert opinion to highlight key principles in the timing of surgery. Shared decision-making regarding timing of surgery after SARS-CoV-2 infection must account for severity of the initial infection; ongoing symptoms of COVID-19; comorbid and functional status; clinical priority and risk of disease progression; and complexity of surgery. For the protection of staff, other patients and the public, planned surgery should not be considered during the period that a patient may be infectious. Precautions should be undertaken to prevent pre- and peri-operative infection, especially in higher risk patients. Elective surgery should not be scheduled within 7 weeks of a diagnosis of SARS-CoV-2 infection unless the risks of deferring surgery outweigh the risk of postoperative morbidity or mortality associated with COVID-19. SARS-CoV-2 causes either transient or asymptomatic disease for most patients, who require no additional precautions beyond a 7-week delay, but those who have persistent symptoms or have been hospitalised require special attention. Patients with persistent symptoms of COVID-19 are at increased risk of postoperative morbidity and mortality even after 7 weeks. The time before surgery should be used for functional assessment, prehabilitation and multidisciplinary optimisation. Vaccination several weeks before surgery will reduce risk to patients and might lessen the risk of nosocomial SARS-CoV-2 infection of other patients and staff. National vaccine committees should consider whether such patients can be prioritised for vaccination. As further data emerge, these recommendations may need to be revised, but the principles presented should be considered to ensure safety of patients, the public and staff.

A Positive Node on Ultrasound-Guided Fine Needle Aspiration Predicts Higher Nodal Burden Than a Positive Sentinel Lymph Node Biopsy in Breast Carcinoma.

INTRODUCTION: Axillary status remains an important prognostic indicator in breast cancer. Certain patients with a positive sentinel node (SLNB) may not benefit from axillary clearance (AC). Uncertainty remains if this approach could be applied to patients diagnosed with axillary metastases on ultrasound-guided fine needle aspiration cytology (USFNAC). The aim of this study was to compare nodal burden in patients with positive USFNAC and a positive SLNB. METHODS: A retrospective study was performed involving all BC patients between 2007 and 2014 who had either pre-operative USFNAC or a SLNB. Patient/tumour characteristics and nodal burden were examined in all patients proceeding to AC. RESULTS: 974 patients were eligible for analysis. 439 patients (45 %) had positive USFNAC and 535 (55 %) had a positive SLNB. USFNAC-positive patients were more likely to undergo mastectomy (Chi-square test; p < 0.001), have extra-nodal extension (p < 0.001), be oestrogen receptor negative (p < 0.001) and be HER2 positive (p < 0.001). The median total number of lymph nodes (LNs) excised during AC was higher in the USFNAC group (Mann-Whitney test; 23 vs. 21; p < 0.001). The median total number of involved LNs was 3 (range 1-47) in FNAC-positive patients versus 1 (range 1-37) in SLNB-positive patients (p < 0.001). The median number of involved LNs in level 1 was 3 in FNAC-positive patients versus 1 in SLNB-positive patients (p < 0.001). Within the SLN-positive group, 49 % of the patients had only one involved LN, 28 % had two nodes involved and 23 % had ≥3. In comparison, within the FNAC-positive group only 13 % of the patients had one involved LN, 12 % had two nodes involved and 74 % had ≥3. CONCLUSION: Patients with positive USFNAC have more aggressive clinico-pathological characteristics and higher nodal burden compared to SLNB-positive patients. Currently, the authors advocate that patients not receiving neoadjuvant chemotherapy, with a positive USFNAC, should proceed directly to an axillary ALND.

Randomized clinical trial of perioperative nerve block and continuous local anaesthetic infiltration via wound catheter versus epidural analgesia in open liver resection (LIVER 2 trial).

BACKGROUND: Analgesia after liver surgery remains controversial. A previous randomized trial of continuous wound infiltration (CWI) versus thoracic epidural analgesia (TEA) after liver surgery (LIVER trial) showed a faster recovery time in the wound infiltration group but better early postoperative pain scores in the TEA group. High-level evidence is, however, limited and opinion remains divided. The aim was to determine whether there is a difference in functional recovery time between patients having CWI plus abdominal nerve blocks versus TEA after liver resection. METHODS: A randomized unblinded clinical trial of patients undergoing open liver resection was commenced in December 2012, with follow-up to August 2014. Patients were randomized to receive either wound catheter and nerve block (CWI group) or TEA for 48 h after surgery. The primary outcome measure was functional recovery time. Secondary outcomes were pain scores, complication rates, inflammatory response and central venous pressure (CVP) during transection. RESULTS: Of 50 patients randomized initially to each group, 44 received TEA and 49 CWI. Median (i.q.r.) recovery time was 6·5 (5-9·75) and 5·75 (4-7) days in the TEA and CWI groups respectively (P = 0·036). Pain scores were not significantly different between the two groups, and there were no differences in morbidity, inflammatory response or CVP during transection. CONCLUSION: Wound infiltration is associated with a reduced time to recovery after open liver resection compared with epidural analgesia. TEA does not offer an advantage over CWI in terms of attenuation of the inflammatory response or pain scores. REGISTRATION NUMBER: NCT01747122 ( http://www.clinicaltrials.gov).

Meta-analysis of ischaemic preconditioning for liver resections.

BACKGROUND: Vascular clamping reduces blood loss during liver resection but leads to ischaemia-reperfusion injury. Ischaemic preconditioning (IP) may reduce this. This study aimed to evaluate IP in liver resection under clamping. METHODS: This was a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating IP in adults undergoing liver resection under either continuous clamping (CC) or intermittent clamping (IC). Primary outcomes were mortality, liver failure and morbidity. Secondary outcomes included duration of operation, blood loss, length of hospital stay, length of intensive therapy unit stay, transfusion requirements, prothrombin time, and bilirubin and aminotransferase levels. Weighted mean differences were calculated for continuous data, and pooled odds ratios (ORs) for dichotomous data. Results were produced with a random-effects model with 95 per cent confidence intervals (c.i.). RESULTS: A total of 2960 records were identified and 11 RCTs included 669 patients (IP 331, control 338). No significant difference in mortality (6 RCTs; IP 186, control 190; OR 1·36, 95 per cent c.i. 0·13 to 13·68; P = 0·80) or morbidity (6 RCTs; IP 186, control 190; OR 0·58, 0·31 to 1·07; P = 0·08) was found for IP plus CC versus CC. Nor was there a significant difference in mortality (4 RCTs; IP 122, control 121; OR 1·33, 0·24 to 7·32; P = 0·74) or morbidity (4 RCTs; IP 122, control 121; OR 0·87, 0·52 to 1·47; P = 0·61) for IP plus (CC or IC) versus IC. No significant differences were found for secondary outcome measures. CONCLUSION: This meta-analysis failed to find a significant benefit of IP in liver resection.

Surgery for colorectal liver metastases.

Half of all patients with colorectal cancer develop metastatic disease. The liver is the principal site for metastases, and surgical resection is the only modality that offers the potential for long-term cure. Appropriate patient selection for surgery and improvements in perioperative care have resulted in low morbidity and mortality rates, resulting in this being the therapy of choice for suitable patients. Modern management of colorectal liver metastases is multimodal incorporating open and laparoscopic surgery, ablative therapies such as radiofrequency ablation or microwave ablation and (neo)adjuvant chemotherapy. The majority of patients with hepatic metastases should be considered for resectional surgery, if all disease can be resected, as this offers the only opportunity for prolonged survival.

Periconceptional folic acid supplementation in a nationally representative sample of mothers.

This study reports recent trends in periconceptional folic acid use in Ireland using archived data from Growing Up in Ireland--the National Longitudinal Study of Children. Of a sample of 10,891 mothers, 6,936 (64%) reported taking folic acid before conception and 10,157 (93%) reported taking folic acid during the first trimester of pregnancy. Younger (OR = 0.38, 95% CI = 0.29-0.50), lower income (OR = 0.59, 95% CI = 0.51-0.68), lower educated (OR = 0.77, 95% CI = 0.66-0.89), and single mothers (OR = 0.46, 95% Cl = 0.40-0.52) were less likely to have taken folic acid pre-conception. A similar pattern was found post-conception with younger (OR = 0.58, 95% Cl = 0.40-0.84), lower income (OR = 0.40, 95% Cl = 0.30-0.53), lower educated (OR = 0.50, 95% Cl = 0.38-0.66), and single mothers (OR = 0.74, 95% CI = 0.60-0.91) less likely to have taken folic acid post-conception. The findings highlight an ongoing need for targeted promotional campaigns to increase supplementation rates among younger and socially disadvantaged mothers.

Muscle Fibre Typology as a Novel Risk Factor for Hamstring Strain Injuries in Professional Football (Soccer): A Prospective Cohort Study.

BACKGROUND: Hamstring strain injuries (HSI) are prevalent in team sports and occur frequently in the later phase of matches. In the search for interindividual factors that determine muscle fatigue and possibly injury risk, muscle fibre typology is a likely candidate. OBJECTIVE: The aim of the study was to determine whether muscle fibre typology is a risk factor for HSI. METHODS: A prospective cohort study was conducted over three seasons in professional football players competing in the Belgian Jupiler Pro League (n = 118) and in the English Premier League (n = 47). A total of 27 HSI were sustained during this period. Muscle fibre typology was non-invasively estimated using proton magnetic resonance spectroscopy and was characterized as a fast, slow, or intermediate typology based on the carnosine concentration in the soleus. A multivariate Cox model was used to identify risk factors for HSI. RESULTS: Football players exhibited a wide variety of muscle typologies (slow 44.9%, intermediate 39.8%, fast 15.3%). In the combined cohort, players with a fast typology displayed a 5.3-fold (95% confidence interval [CI] 1.92-14.8; P = 0.001) higher risk of sustaining an index HSI than slow typology players. This was also independently observed in both leagues separately as, respectively, a 6.7-fold (95% CI 1.3-34.1; P = 0.023) and a 5.1-fold (95% CI 1.2-20.4; P = 0.023) higher chance was found in fast typology players than in slow typology players of the Jupiler Pro League and the Premier League cohort. CONCLUSION: We identified muscle fibre typology as a novel and potent risk factor for HSI in team sports.

The Scottish Liver Transplant Unit: current and future perspectives.

The Scottish Liver Transplant Unit (SLTU) opened in 1992 and has now performed over 900 liver transplants. During this time there have been major changes in both organ donation and transplantation. Currently liver transplantation is restricted by limited organ supply. Scotland has one of the lowest rates of organ donation in Europe and one of the most rapidly increasing rates of cirrhosis. The consequent waiting list mortality has driven innovations including increasing use of marginal grafts, organs donated after cardiac death, split-liver transplants and the development of living-donor liver transplantation. To maintain liver transplantation, there is an urgent need to increase organ donation rates and to find novel treatments which optimize outcomes from marginal grafts. This review addresses the surgical aspects of liver transplantation and how these have evolved over the two past decades. Major changes are currently underway in organ donation organization, and there is continuing refinement of organ treatment and storage. A number of measures to maintain and improve organ preservation and function are currently being evaluated in clinical trials, and cell therapy holds significant potential for the future. Scotland has a rising need for liver transplantation and the SLTU continues to provide high-quality care and to be at the forefront of the latest advances in organ transplantation.

Genetic control of diabetes and insulitis in the nonobese diabetic (NOD) mouse.

Genetic analysis of the development of diabetes and insulitis has been performed in the nonobese diabetic (NOD) mouse strain, a model of insulin-dependent (type I) diabetes mellitus. (NOD X C57BL/10)F1, F2, and (F1 X NOD) first-, second-, and third-backcross generations were studied. The data obtained were consistent with the hypothesis that diabetes is controlled by at least three functionally recessive diabetogenic genes, or gene complexes, one of which is linked to the MHC of the NOD. In contrast, pancreatic inflammation leading to insulitis was found to be controlled by a single incompletely dominant gene. One of the two diabetogenic loci that is not linked to the MHC appears to be essential for the development of severe insulitis. This diabetogenic gene may be identical to the gene that controls the initiation of the autoimmune response that progresses to insulitis. Although this gene appears to be functionally recessive in its control of diabetes, it is incompletely dominant in its control of insulitis. The MHC-linked diabetogenic gene, although not required for the development of insulitis, apparently influences the progression of the autoimmune response since NOD MHC homozygotes in the backcross generations displayed the highest incidence and most severe cases of insulitis. Interestingly, we have found two MHC heterozygous backcross females that have become diabetic, suggesting that either the MHC-linked diabetogenic gene is not strictly recessive or that a recombination event has occurred between the diabetogenic gene and the K or I-A regions of the MHC. The third diabetogenic locus appears to influence the progression of severe insulitis to overt diabetes. In animals homozygous at this locus, diabetes may result from a decreased ability to develop a protective suppressor response to the autoimmune process.

Practical barriers to the implementation of early goal directed therapy in the UK: trainee skills and awareness.

The Surviving Sepsis Campaign (SSC) recommends Early Goal Directed Therapy (EGDT) in the treatment of septic shock, which requires key critical care skills and knowledge. This study evaluates the availability of these skills in Specialist Registrars in acute hospital specialities in the UK. A questionnaire was sent to Specialist Registrars in Anaesthetics, General Surgery and General Medicine throughout Scotland. One hundred and eighty five responses were obtained. One hundred percent of anaesthetists, 70% of surgeons and 51% of physicians were aware of EGDT Only 62 trainees (6% of surgeons, 79% of anaesthetists, 19% of physicians) had the full complement of skills and knowledge to implement EGDT. This study demonstrates that non-anaesthetic registrars in the UK lack both knowledge and skills required to provide EGDT. The main deficit was in awareness, demonstrating that knowledge of EGDT is not penetrating into specialities beyond anaesthesia. It is now time for the SSC to specifically target non-anaesthetic specialities.

American football and other sports injuries may cause migraine/persistent pain decades later and can be treated successfully with electrical twitch-obtaining intramuscular stimulation (ETOIMS).

INTRODUCTION: Autonomous twitch elicitation at myofascial trigger points from spondylotic radiculopathies-induced denervation supersensitivity can provide favourable pain relief using electrical twitch-obtaining intramuscular stimulation (ETOIMS). AIM: To provide objective evidence that ETOIMS is safe and efficacious in migraine and persistent pain management due to decades-old injuries to head and spine from paediatric American football. METHODS AND MATERIALS: An 83-year-old mildly hypertensive patient with 25-year history of refractory migraine and persistent pain self-selected to regularly receive fee-for-service ETOIMS 2/week over 20 months. He had 180 sessions of ETOIMS. Pain levels, blood pressure (BP) and heart rate/pulse were recorded before and immediately after each treatment alongside highest level of clinically elicitable twitch forces/session, session duration and intervals between treatments. Twitch force grades recorded were from 1 to 5, grade 5 twitch force being strongest. RESULTS: Initially, there was hypersensitivity to electrical stimulation with low stimulus parameters (500 µs pulse-width, 30 mA stimulus intensity, frequency 1.3 Hz). This resolved with gradual stimulus increments as tolerated during successive treatments. By treatment 27, autonomous twitches were noted. Spearman's correlation coefficients showed that pain levels are negatively related to twitch force, number of treatments, treatment session duration and directly related to BP and heart rate/pulse. Treatment numbers and session durations directly influence twitch force. At end of study, headaches and quality of life improved, hypertension resolved and antihypertensive medication had been discontinued. CONCLUSIONS: Using statistical process control methodology in an individual patient, we showed long-term safety and effectiveness of ETOIMS in simultaneous diagnosis, treatment, prognosis and prevention of migraine and persistent pain in real time obviating necessity for randomised controlled studies.

Inhibition of murine K-BALB and CT26 tumour growth using a Semliki Forest virus vector with enhanced expression of IL-18.

The enhanced Semliki Forest virus vector (SFV10-E), an RNA-based suicide expression vector system, expresses foreign genes at levels up to 10x higher than the original SFV10 vector. This vector has been used previously to express interleukin-12 for a tumour treatment study in a BALB/c murine model. Interleukin-18, an IFN-gamma-inducing cytokine, plays a key role in the early induction of T helper1 (Th1) cell-mediated immune responses in addition to anti-angiogenic activity. In this study, the murine IL-18 gene along with an Ig-kappa leader sequence was cloned into the SFV10-E vector. The pSFV10-E-IL-18 construct was characterised in vitro for levels of expression and secretion, and the production of biologically active IL-18 was confirmed. An in vivo tumour treatment study using high titre rSFV10-E-IL-18 virus-like particles to treat subcutaneous K-BALB and CT26 tumours in BALB/c mice demonstrated therapeutic efficacy including the disappearance of tumour cells in a minority of treated animals. Tumour regression was associated with induction of avascular and suppurative necrosis.

Now, later or never? Challenges associated with hepatitis C treatment.

BACKGROUND AND AIMS: Of the 259,000 Australians estimated to have a hepatitis C virus infection, very few have received antiviral therapy. This study identifies personal, psychological and structural barriers associated with decisions to begin treatment and the challenges associated with adhering to a demanding treatment regimen. METHODS: Between August 2003 and May 2004, 224 people living in Victoria who were hepatitis C antibody positive completed a 78-item survey instrument. Participants were recruited from a variety of settings and included those who were on treatment for hepatitis C (n=45); previously on treatment (n=65); and people who had never experienced treatment (n=114). RESULTS: The average age of the participants was 43 years. Men (n=29) were more likely than women (n=15) to be receiving treatment. Participants diagnosed in the past five years (31%) were more likely to be receiving treatment compared with those diagnosed more than five years ago (14%). Participants rated the effectiveness of treatment as the most important factor in influencing their decision to begin treatment. Side effects were rated the biggest challenge to adhering to treatment and were also rated as the most important consideration for those who decided against treatment. CONCLUSIONS: This study has shown many decisions and challenges affect the uptake of, and adherence to, hepatitis C treatment. Dissemination and promotion of information about increased effectiveness of new treatments will greatly influence decisions to begin treatment. Careful management and minimisation of side effects are also essential to improve uptake and increase adherence to hepatitis C treatment.

Effect of analgesic modality on outcome following open liver surgery: a systematic review of postoperative analgesia.

Postoperative analgesia following liver resection remains controversial. The traditional standard of care of thoracic epidural is increasingly questioned due to perceived associated complications and delays to recovery. Evidence supporting alternative analgesic techniques is emerging however best practice is not yet established. This review aimed to evaluate the literature to assess the optimum analgesic technique following liver resection. A systematic review was conducted of trials evaluating analgesic methods in open liver surgery. Primary outcome was the postoperative complication rate. Secondary outcomes were length of stay and pain scores. Fourteen trials matching the inclusion criteria were analysed. No difference was observed in systemic complication rates between analgesic modalities. Epidural was associated with prolonged length of stay when compared with continuous wound infiltration and intrathecal morphine. Epidural offered equivalent or superior pain scores when compared to alternative techniques. In summary current evidence suggests alternative analgesic modalities may provide favorable recovery outcomes following liver surgery but consistent evidence is limited. Epidurals provide superior pain relief to alternatives but this does not translate into reduced length of stay or complication rate following liver surgery.

Effects of methomyl and ethanol on behavior in the Sprague-Dawley rat.

Emotional behavior and activity levels were studied following administration of ethanol and/or a carbamate pesticide, methomyl, to rats via a ground chow diet. Acetylcholinesterase levels were lowered following the experimental diets. The group having the greatest reduction in AChE, the methomyl group, showed less evidence for habituation in an open-field test. No differences relative to control subjects were noted on handling and muricide tests.

The results at nine to twelve years of the use of a hydroxyapatite-coated femoral stem.

We describe the clinical and radiological outcome of 100 consecutive total hip replacements in 86 patients using the JRI Furlong hydroxyapatite-coated femoral component. The follow-up was 100% at a mean of ten years (9.0 to 12.0). All 54 living patients (62 hips) were examined annually. Their mean Merle d'Aubigné score was 5.8/5.6/4.6. A total of 32 patients had died. Their notes at the last annual assessment recorded a similar outcome to that of the living patients. Radiographs showed no radiolucent lines around any femoral component and there were no signs of impending failure. One patient required excision arthroplasty, but the femoral component had been bonded satisfactorily. There have been no other revisions of femoral components. Our findings suggest that the hydroxyapatite coating gives a satisfactory prosthesis-bone interface which is preferable to any other system.

The effects of respite care on informal carers' well-being: a systematic review.

PURPOSE: The provision of respite care is a common method employed to reduce the burden on those who care for individuals with a chronic illness or disability. The aim of the present review was to examine research on respite provision with a view to establishing what effect it has on carers. METHOD: A literature search was conducted for studies examining the effect of respite provision on carers, 'Psyclit', 'Medline' and Social Science Citation Index computerized databases were utilized, followed by a search of the reference sections of relevant studies. RESULTS: The search yielded 29 studies, from which there was little evidence that respite intervention has either a consistent or enduring beneficial effect on carers' well-being. This may be due in part to the fact that the majority of the work conducted has been methodologically poor. Also significant, however, might be that the findings suggest respite care often fails to facilitate the maintenance of socially supportive relationships, which may moderate strain after respite has ended. CONCLUSIONS: A more 'carer-centred' approach is required in both the provision and evaluation of respite care intervention. This approach would address the experiences of both caregiver and care-recipient during the respite period.