Systematic review of survival following liver or lung metastasectomy for metastatic anal squamous cell carcinoma.

INTRODUCTION: Metastatic anal squamous cell carcinoma (SCC) carries a poor prognosis and the evidence base for surgical resection of metastases remains limited. The aim of this study was to establish the survival outcomes for patients undergoing metastasectomy for anal SCC. METHODS: A systematic review was performed using the MEDLINE®, Embase®, Cochrane and PubMed® databases. Studies were considered for inclusion in the review if they involved patients aged >18 years with a diagnosis of stage IV anal SCC who underwent metastasectomy for liver and/or lung metastases. The primary outcome measure was overall survival. Secondary outcome measures were disease free survival, early morbidity according to the Clavien-Dindo classification and quality of life, measured using a validated scoring tool. Risk of bias was assessed with the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool. RESULTS: There were 10 studies with a total of 98 patients. There was heterogeneity in results reporting, with recurrence free survival the most reported outcome. For all studies reporting on liver metastasectomy, the one-year overall survival rate was 87%. In studies with adequate follow-up reported, the three and five-year overall survival rates were 53% and 38% respectively. Only one study reported on lung metastasectomy patients; the overall median survival was 24 months. None of the studies reported on quality of life measures. The ROBINS-I tool identified a critical risk of bias in six studies, a serious risk in one study and a moderate risk in three studies. CONCLUSIONS: The evidence base for metastasectomy in metastatic anal SCC is limited. Further information is required to inform future treatment methods and use of a standardised outcomes reporting method is needed to support this.

Peri-operative cardiac arrest: epidemiology and clinical features of patients analysed in the 7th National Audit Project of the Royal College of Anaesthetists.

The 7th National Audit Project of the Royal College of Anaesthetists studied peri-operative cardiac arrest in the UK, a topic of importance to patients, anaesthetists and surgeons. Here we report the results of the 12-month registry, from 16 June 2021 to 15 June 2022, focusing on epidemiology and clinical features. We reviewed 881 cases of peri-operative cardiac arrest, giving an incidence of 3 in 10,000 anaesthetics (95%CI 3.0-3.5 per 10,000). Incidence varied with patient and surgical factors. Compared with denominator survey activity, patients with cardiac arrest: included more males (56% vs. 42%); were older (median (IQR) age 60.5 (40.5-80.5) vs. 50.5 (30.5-70.5) y), although the age distribution was bimodal, with infants and patients aged > 66 y overrepresented; and were notably more comorbid (73% ASA physical status 3-5 vs. 27% ASA physical status 1-2). The surgical case-mix included more weekend (14% vs. 11%), out-of-hours (19% vs. 10%), non-elective (65% vs. 30%) and major/complex cases (60% vs. 28%). Cardiac arrest was most prevalent in orthopaedic trauma (12%), lower gastrointestinal surgery (10%), cardiac surgery (9%), vascular surgery (8%) and interventional cardiology (6%). Specialities with the highest proportion of cases relative to denominator activity were: cardiac surgery (9% vs. 1%); cardiology (8% vs. 1%); and vascular surgery (8% vs. 2%). The most common causes of cardiac arrest were: major haemorrhage (17%); bradyarrhythmia (9%); and cardiac ischaemia (7%). Patient factors were judged a key cause of cardiac arrest in 82% of cases, anaesthesia in 40% and surgery in 35%.

The incidence of potentially serious complications during non-obstetric anaesthetic practice in the United Kingdom: an analysis from the 7th National Audit Project (NAP7) activity survey.

Complications and critical incidents arising during anaesthesia due to patient, surgical or anaesthetic factors, may cause harm themselves or progress to more severe events, including cardiac arrest or death. As part of the 7th National Audit Project of the Royal College of Anaesthetists, we studied a prospective national cohort of unselected patients. Anaesthetists recorded anonymous details of all cases undertaken over 4 days at their site through an online survey. Of 416 hospital sites invited to participate, 352 (85%) completed the survey. Among 24,172 cases, 1922 discrete potentially serious complications were reported during 1337 (6%) cases. Obstetric cases had a high reported major haemorrhage rate and were excluded from further analysis. Of 20,996 non-obstetric cases, 1705 complications were reported during 1150 (5%) cases. Circulatory events accounted for most complications (616, 36%), followed by airway (418, 25%), metabolic (264, 15%), breathing (259, 15%), and neurological (41, 2%) events. A single complication was reported in 851 (4%) cases, two complications in 166 (1%) cases and three or more complications in 133 (1%) cases. In non-obstetric elective surgery, all complications were 'uncommon' (10-100 per 10,000 cases). Emergency (urgent and immediate priority) surgery accounted for 3454 (16%) of non-obstetric cases but 714 (42%) of complications with severe hypotension, major haemorrhage, severe arrhythmias, septic shock, significant acidosis and electrolyte disturbances all being 'common' (100-1000 per 10,000 cases). Based on univariate analysis, complications were associated with: younger age; higher ASA physical status; male sex; increased frailty; urgency and extent of surgery; day of the week; and time of day. These data represent the rates of potentially serious complications during routine anaesthesia care and may be valuable for risk assessment and patient consent.

Efficacy of immune checkpoint inhibitors for the treatment of advanced melanoma in patients with concomitant chronic lymphocytic leukemia.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the management of advanced melanoma (AM). However, data on ICI effectiveness have largely been restricted to clinical trials, thereby excluding patients with co-existing malignancies. Chronic lymphocytic leukemia (CLL) is the most prevalent adult leukemia and is associated with increased risk of melanoma. CLL alters systemic immunity and can induce T-cell exhaustion, which may limit the efficacy of ICIs in patients with CLL. We, therefore, sought to examine the efficacy of ICI in patients with these co-occurring diagnoses. PATIENTS AND METHODS: In this international multicenter study, a retrospective review of clinical databases identified patients with concomitant diagnoses of CLL and AM treated with ICI (US-MD Anderson Cancer Center, N = 24; US-Mayo Clinic, N = 15; AUS, N = 19). Objective response rates (ORRs), assessed by RECIST v1.1, and survival outcomes [overall survival (OS) and progression-free survival (PFS)] among patients with CLL and AM were assessed. Clinical factors associated with improved ORR and survival were explored. Additionally, ORR and survival outcomes were compared between the Australian CLL/AM cohort and a control cohort of 148 Australian patients with AM alone. RESULTS: Between 1997 and 2020, 58 patients with concomitant CLL and AM were treated with ICI. ORRs were comparable between AUS-CLL/AM and AM control cohorts (53% versus 48%, P = 0.81). PFS and OS from ICI initiation were also comparable between cohorts. Among CLL/AM patients, a majority were untreated for their CLL (64%) at the time of ICI. Patients with prior history of chemoimmunotherapy treatment for CLL (19%) had significantly reduced ORRs, PFS, and OS. CONCLUSIONS: Our case series of patients with concomitant CLL and melanoma demonstrate frequent, durable clinical responses to ICI. However, those with prior chemoimmunotherapy treatment for CLL had significantly worse outcomes. We found that CLL disease course is largely unchanged by treatment with ICI.

Feasibility of delivering foot and ankle surgical courses in a partnership in Eastern, Central and Sothern Africa.

BACKGROUND: Foot and ankle pathology if not treated appropriately and in a timely manner can adversely affect both disability and quality adjusted life years. More so in the low- and middle-income countries where ambulation is the predominant means of getting around for the majority of the population in order to earn a livelihood. This has necessitated the equipping of the new generation of orthopaedic surgeons with the expertise and skills set to manage these conditions. To address this need, surgeons from the British Orthopaedic Foot & Ankle Society (BOFAS) and College of Surgeons of Eastern, Central and Southern Africa (COSECSA) transferred the "Principles of Foot and Ankle Surgery" course to an African regional setting. The course was offered to surgical trainees from 14-member countries of the COSECSA region and previously in the UK. The faculty was drawn from practicing surgeons experienced in both surgical education and foot and ankle surgery. The course comprises didactic lectures, case-based discussions in small groups, patient evaluations and guided surgical dissections on human cadavers. It was offered free to all participants. The feasibility of the course was evaluated using the model defined by Bowen considering the eight facets of acceptability, demand, implementation, practicality, adaptation, integration, expansion and limited efficacy. At the end of the course participants were expected to give verbal subjective feedback and objective feedback using a cloud based digital feedback questionnaire. The course content was evaluated by the participants as "Poor", "Below average", "Average", "Good" and "Excellent", which was converted into a value from 1-5 for analysis. The non-parametric categorical data was analysed using the Two-sample Wilcoxon rank-sum (Mann-Whitney) test, and significance was considered to be p < 0.05. RESULTS: Six courses in total were held between 2018 and 2020. Three in the UK and three in the COSECSA region. There were 78 participants in the three UK courses and 96 in the three courses run in the COSECSA region. Hundred percent of the UK participants and 97% of the COSECSA participants completed the feedback. Male to female ratio was 4:1 for the UK courses and 10:1 for the COSECSA Courses. In both regions all the participants responded that they would recommend the course to their colleagues. Among the COSECSA participants 91% reported that the course was pitched at the right level, which is similar to the 89% of the UK participants (p = 0.28). CONCLUSION: The BOFAS Principles of Foot and Ankle Surgery course design provides core knowledge, with an emphasis on clinical examination techniques of the foot and ankle, while at the same time, caters for the anticipated difference in the local clinical case mix and resources. This study establishes that by attending the course surgical trainees can achieve their learning goals in foot and ankle surgery with the same high quality qualitative and quantitative feedback in both regions. This would improve their clinical practice and confidence. The multifaceted approach adopted in this course blending didactic teaching, small group discussions, interactive sessions, case-based discussions, cadaveric surgical skills training printed educational materials and feedback helped fulfil these educational objectives. Working in partnership with local expert orthopaedic surgeons from a number of Sub-Saharan countries, was key to adapting the course to local pathology and the COSECSA setting.

Risk-Reducing Salpingo-Oophorectomy and the Use of Hormone Replacement Therapy Below the Age of Natural Menopause: Scientific Impact Paper No. 66 October 2021: Scientific Impact Paper No. 66.

This paper deals with the use of hormone replacement therapy (HRT) after the removal of fallopian tubes and ovaries to prevent ovarian cancer in premenopausal high risk women. Some women have an alteration in their genetic code, which makes them more likely to develop ovarian cancer. Two well-known genes which can carry an alteration are the BRCA1 and BRCA2 genes. Examples of other genes associated with an increased risk of ovarian cancer include RAD51C, RAD51D, BRIP1, PALB2 and Lynch syndrome genes. Women with a strong family history of ovarian cancer and/or breast cancer, may also be at increased risk of developing ovarian cancer. Women at increased risk can choose to have an operation to remove the fallopian tubes and ovaries, which is the most effective way to prevent ovarian cancer. This is done after a woman has completed her family. However, removal of ovaries causes early menopause and leads to hot flushes, sweats, mood changes and bone thinning. It can also cause memory problems and increases the risk of heart disease. It may reduce libido or impair sexual function. Guidance on how to care for women following preventative surgery who are experiencing early menopause is needed. HRT is usually advisable for women up to 51 years of age (average age of menopause for women in the UK) who are undergoing early menopause and have not had breast cancer, to minimise the health risks linked to early menopause. For women with a womb, HRT should include estrogen coupled with progestogen to protect against thickening of the lining of the womb (called endometrial hyperplasia). For women without a womb, only estrogen is given. Research suggests that, unlike in older women, HRT for women in early menopause does not increase breast cancer risk, including in those who are BRCA1 and BRCA2 carriers and have preventative surgery. For women with a history of receptor-negative breast cancer, the gynaecologist will liaise with an oncology doctor on a case-by-case basis to help to decide if HRT is safe to use. Women with a history of estrogen receptor-positive breast cancer are not normally offered HRT. A range of other therapies can be used if a woman is unable to take HRT. These include behavioural therapy and non-hormonal medicines. However, these are less effective than HRT. Regular exercise, healthy lifestyle and avoiding symptom triggers are also advised. Whether to undergo surgery to reduce risk or not and its timing can be a complex decision-making process. Women need to be carefully counselled on the pros and cons of both preventative surgery and HRT use so they can make informed decisions and choices.

Premature ovarian insufficiency: the need for evidence on the effectiveness of hormonal therapy.

Premature ovarian insufficiency (POI) - the loss of ovarian function before the age of 40 years, a decade before natural menopause - is a life-changing diagnosis for women. POI causes significant short-term and long-term morbidity related to estrogen deficiency. The condition is managed by providing exogenous estrogen replacement, usually as the oral contraceptive pill or hormone therapy. These preparations have different estrogen formulations and may have differing benefits and risks. At present, there are no robust data to inform clinical recommendations and women's decision-making about treatment that they may be taking for many years. The POISE study (Premature Ovarian Insufficiency Study of Effectiveness of hormonal therapy) has been designed to determine whether hormone therapy is superior to combined oral contraceptives on important clinical outcomes and patient-reported symptoms, based on the hypothesis that hormone therapy provides more physiological continuous hormone supplementation with natural estrogens. The study is an open and pragmatic, parallel, randomized controlled trial. The primary outcome is absolute bone mineral density assessed by dual-energy X-ray absorptiometry of the lumbar spine after 2 years of treatment. The study will also investigate cardiovascular markers, symptom relief and acceptability of treatment, and will continue to collect long-term data on fractures and cardiovascular events. Results will inform future guidance on management of POI.

Histopathological features of complete pathological response predict recurrence-free survival following neoadjuvant targeted therapy for metastatic melanoma.

BACKGROUND: Recent clinical trials demonstrated the safety and efficacy of neoadjuvant dabrafenib and trametinib (DT) among patients with surgically resectable clinical stage III BRAFV600E/K mutant melanoma. Although patients achieving a complete pathological response (pCR) exhibited superior recurrence-free survival (RFS) versus those who did not, 30% of pCR patients relapsed. We sought to identify whether histopathological features of the pathological response further delineated risk of relapse. METHODS: Surgical resection specimens from DT-treated patients in two phase 2 clinical trials were reviewed. Histopathological features, including relative amounts of viable tumour, necrosis, melanosis, and fibrosis (hyalinized or immature/proliferative) were assessed for associations with patient outcomes. RESULTS: Fifty-nine patients underwent surgical resection following neoadjuvant DT. Patients achieving pCR (49%) had longer RFS compared with patients who did not (P = 0.005). Patients whose treated tumour showed any hyalinized fibrosis had longer RFS versus those without (P = 0.014), whereas necrosis (P = 0.012) and/or immature/proliferative fibrosis (P = 0.026) correlated with shorter RFS. Multivariable analyses showed absence of pCR or presence of immature fibrosis independently predicted shorter RFS. Among pCR patients, mature/hyalinized-type fibrosis correlated with improved RFS (P = 0.035). CONCLUSIONS: The extent and composition of the pathological response following neoadjuvant DT in BRAFV600E/K mutant melanoma correlates with RFS, including pCR patients. These findings support the need for detailed histological analysis of specimens collected after neoadjuvant therapy.

Patient-reported outcomes after 10-year follow-up of intensive, multifactorial treatment in individuals with screen-detected type 2 diabetes: the ADDITION-Europe trial.

AIMS: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial. METHODS: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis. RESULTS: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]. CONCLUSIONS: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care.

Isolated primary bone tumours of the lesser trochanter: Demographics, diagnosis and management.

Primary bone tumours arising from the lesser trochanter (LT) are rare and the literature describing them is sparse. In this paper, we describe the largest series of LT tumours describing the demographics, diagnosis and management. METHODS: A retrospective search of prospectively maintained radiology and oncology databases was performed to identify bone tumours of the LT diagnosed between 2007 and 2018. Metastatic lesions were excluded. All cases were re-reviewed by a senior Radiologist and all case of isolated tumours of the LT were included. RESULTS: 23 cases of isolated LT tumours were identified. There were 15 males and 8 females. Mean age of our cohort was 32 (14-63) years. Most (n = 19, 82.6%) cases had classic radiological (Radiographic, MR Imaging and CT) features and therefore did not undergo biopsy. 4 patients had equivocal radiological investigations that required biopsy to confirm the diagnosis. MR imaging was the most commonly used imaging modality for diagnosis (n = 17, 73.9%)There was a broad range of tumour subtypes, and osteochondroma (n = 17, 73.9%) the most frequently diagnosed. Surgical excision was performed in 4 patients (all osteochondromas) and 4 patients underwent therapeutic radiological guided hip injections for symptomatic relief. The remaining cases were managed conservatively and where they were identified incidentally, no intervention was required. CONCLUSION: We report the largest case series of isolated primary bone tumours of the LT. All isolated primary bone tumours of LT are benign. Osteochondroma is the most common. The diagnosis can be made with on radiological investigations in most patients.

Trauma to the medial ray of the foot: A classification of patterns of injury and their management.

AIMS: Fractures and dislocations of the midfoot are relatively uncommon but can be life changing injuries. Within the literature, there has been scant specific reference to the identification and management of medial ray injuries in midfoot trauma. Moreover, it is appreciated that these injuries are associated with poor outcomes. We aim to clearly define these injury characteristics and demonstrate fixation techniques. PATIENTS AND METHODS: A retrospective review of the case notes and imaging was conducted for operatively treated midfoot injuries between January 2013 and January 2018. RESULTS: 161 patients were identified, 31 of these with imaging and operative diagnosis suggestive of medial ray injury. Studying these 31 injuries revealed five patterns of injury. CONCLUSION: When treating midfoot trauma, it is important to fully understand the injury pattern as this dictates the principles and techniques of fixation. Identification and knowledge of these five injury patterns will aid surgeons in future management of these injuries and may improve treatment outcomes.

Independent or simultaneous lowering of core and skin temperature has no impact on self-paced intermittent running performance in hot conditions.

PURPOSE: To investigate the effects of lowering core (Tgi) and mean skin temperature (Tsk) concomitantly and independently on self-paced intermittent running in the heat. METHODS: 10 males (30.5 ± 5.8 years, 73.2 ± 14.5 kg, 176.9 ± 8.0 cm, 56.2 ± 6.6 ml/kg/min) completed four randomised 46-min self-paced intermittent protocols on a non-motorised treadmill in 34.4 ± 1.4 °C, 36.3 ± 4.6% relative humidity. 30-min prior to exercise, participants were cooled via either ice slurry ingestion (INT); a cooling garment (EXT); mixed-cooling (ice slurry and cooling garment concurrently) (MIX); or no-cooling (CON). RESULTS: At the end of pre-cooling and the start of exercise Tgi were lower during MIX (36.11 ± 1.3 °C) compared to CON (37.6 ± 0.5 °C) and EXT (36.9 ± 0.5 °C, p < 0.05). Throughout pre-cooling Tsk and thermal sensation were lower in MIX compared to CON and INT, but not EXT (p < 0.05). The reductions in thermophysiological responses diminished within 10-20 min of exercise. Despite lowering Tgi, Tsk, body temperature (Tb), and thermal sensation prior to exercise, the distances covered were similar (CON: 6.69 ± 1.08 km, INT: 6.96 ± 0.81 km, EXT: 6.76 ± 0.65 km, MIX 6.87 ± 0.70 km) (p > 0.05). Peak sprint speeds were also similar between conditions (CON: 25.6 ± 4.48 km/h, INT: 25.4 ± 3.6 km/h, EXT: 26.0 ± 4.94 km/h, MIX: 25.6 ± 3.58 km/h) (p > 0.05). Blood lactate, heart rate and RPE were similar between conditions (p > 0.05). CONCLUSION: Lowering Tgi and Tsk prior to self-paced intermittent exercise did not improve sprint, or submaximal running performance.

Association of depression and anxiety with clinical, sociodemographic, lifestyle and environmental factors in South Asian and white European individuals at high risk of diabetes.

AIM: To investigate the prevalence and correlates of depressive and anxiety symptoms within South Asian and white European populations at high risk of developing Type 2 diabetes. METHODS: Data were collected at baseline, and at 12, 24 and 36 months from 1429 white European individuals (age 64±7 years, 35.8% women) and 160 South Asian individuals (age 59±9 years, 30.6% women) who were at high risk of Type 2 diabetes and who took part in two Type 2 diabetes prevention trials in Leicestershire, UK. The Hospital Anxiety and Depression Scale was administered during each study visit. Clinical, sociodemographic, lifestyle and environmental data were collected. RESULTS: At baseline, the burden of depressive symptoms varied by ethnic group and gender, with 9.9% of white European men, 14.9% of white European women, 23.6% of South Asian men and 29.2% of South Asian women exceeding the cut-off score for mild-to-severe depression. During the course of the study and after adjustment for clinical, sociodemographic, lifestyle and environmental factors, depressive symptoms remained higher in the South Asian compared to the white European participants [score higher by 1.5, 95% CI 0.9-2.1]. Levels of anxiety were also higher in the South Asian participants, although associations were attenuated after adjustment. Social deprivation, BMI, proximity to fast-food outlets and physical activity were correlates for depression in both the South Asian and white European participants. CONCLUSIONS: A higher burden of depressive symptoms was consistently evident among the South Asian individuals, even after adjustment for multiple covariates. It is important to understand both the reasons why these differences are present, to help reduce health inequalities, and whether higher levels of depressive symptoms affect the uptake of and retention rates in diabetes prevention programmes in South Asian communities.

Mortality for emergency laparotomy is not affected by the weekend effect: a multicentre study.

INTRODUCTION: The 'weekend effect' describes variation in outcomes of patients treated over the weekend compared with those treated during weekdays. This study examines whether a weekend effect exists for patients who undergo emergency laparotomy. MATERIALS AND METHODS: Data entered into the National Emergency Laparotomy Audit between 2014 and 2017 at four NHS trusts in England and Wales were analysed. Patients were grouped into those admitted on weekdays and those on weekends (Friday 5pm to Monday 8am). Patient factors, markers of quality of care and patient outcomes were compared. Secondary analysis was performed according to the day of surgery. RESULTS: After exclusion of patients who underwent laparotomy more than one week after admission to hospital, a total of 1717 patients (1138 patients admitted on weekdays and 579 admitted on weekends) were analysed. Age, preoperative lactate and P-POSSUM scores were not significantly different between the two groups. Time from admission to consultant review, decision to operate, commencement of antibiotics and theatre were not significantly different. Grades of operating surgeon were also similar in both groups. Inpatient 60-day mortality was 12.5% on weekdays and 12.8% on weekends (P = 0.878). Median length of postoperative stay was 12 days in both groups. When analysed according to day of surgery, only number of hours from admission to antibiotics (12.8 weekday vs 9.4 weekend, P = 0.046) and number of hours to theatre (26.5 weekday vs 24.1 hours weekend, P = 0.020) were significantly different. DISCUSSION: Quality of care and clinical outcomes for patients undergoing emergency laparotomy during the weekend are not significantly different to those carried out during weekdays.

Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials.

In individuals with type 2 diabetes, glycaemic control and cardiovascular risk factor management reduces the likelihood of late-stage diabetic complications. Guidelines recommend treatment goals targeting HbA1c, body weight, blood pressure, and low-density lipoprotein cholesterol. Development of new treatments for type 2 diabetes requires an understanding of their mechanism and efficacy, as well as their relative effects compared to other treatment choices, plus demonstration of cardiovascular safety. Subcutaneous semaglutide is a glucagon-like peptide-1 receptor agonist currently approved in several countries for once-weekly treatment of type 2 diabetes. Semaglutide works via the incretin pathway, stimulating insulin and inhibiting glucagon secretion from the pancreatic islets, leading to lower blood glucose levels. Semaglutide also decreases energy intake by reducing appetite and food cravings, and lowering relative preference for fatty, energy-dense foods. Semaglutide was evaluated in the SUSTAIN clinical trial programme in over 8000 patients across the spectrum of type 2 diabetes. This review details the efficacy and safety profile of semaglutide in the SUSTAIN 1-5 and 7 trials, and its cardiovascular safety profile in the SUSTAIN 6 trial. Semaglutide consistently demonstrated superior and sustained glycemic control and weight loss vs. all comparators evaluated. In SUSTAIN 6, involving patients at high risk of cardiovascular disease, semaglutide significantly decreased the occurrence of cardiovascular events compared with placebo/standard of care (hazard ratio 0.74, P < 0.001 for non-inferiority). Through a comprehensive phase 3 clinical trial program, we have a detailed understanding of semaglutide's efficacy, safety, cardiovascular effects and comparative role in the treatment of type 2 diabetes.

Meta-analysis of the influence of lifestyle changes for preoperative weight loss on surgical outcomes.

BACKGROUND: The aim was to investigate whether preoperative weight loss results in improved clinical outcomes in surgical patients with clinically significant obesity. METHODS: This was a systematic review and aggregate data meta-analysis of RCTs and cohort studies. PubMed, MEDLINE, Embase and CINAHL Plus databases were searched from inception to February 2018. Eligibility criteria were: studies assessing the effect of weight loss interventions (low-energy diets with or without an exercise component) on clinical outcomes in patients undergoing any surgical procedure. Data on 30-day or all-cause in-hospital mortality were extracted and synthesized in meta-analyses. Postoperative thromboembolic complications, duration of surgery, infection and duration of hospital stay were also assessed. RESULTS: A total of 6060 patients in four RCTs and 12 cohort studies, all from European and North American centres, were identified. Most were in the field of bariatric surgery and all had some methodological limitations. The pooled effect estimate suggested that preoperative weight loss programmes were effective, leading to significant weight reduction compared with controls: mean difference -7·42 (95 per cent c.i. -10·09 to -4·74) kg (P < 0·001). Preoperative weight loss interventions were not associated with a reduction in perioperative mortality (odds ratio 1·41, 95 per cent c.i. 0·24 to 8·40; I2 = 0 per cent, P = 0·66) but the event rate was low. The weight loss groups had shorter hospital stay (by 27 per cent). No differences were found for morbidity. CONCLUSION: This limited preoperative weight loss has advantages but may not alter the postoperative morbidity or mortality risk.

Multimorbidity and lifestyle factors among adults with intellectual disabilities: a cross-sectional analysis of a UK cohort.

BACKGROUND: Multimorbidity [two or more conditions in addition to intellectual disability (ID)] is known to be more common among people with ID. However, the relationship between multimorbidity and lifestyle factors is currently unknown. The aim of this study was to determine the prevalence of multimorbidity in a population of adults with ID. We also aimed to identify risk factors, including lifestyle factors, for multimorbidity in this population. METHODS: This was a cross-sectional analysis using data from a diabetes screening study of 920 adults aged 18-74 years with ID living in Leicestershire, UK. We described comorbidities and the prevalence of multimorbidity in this population. We explored the relationship between multimorbidity and age, gender, ethnicity, severity of ID, socio-economic status, physical activity, sedentary behaviour, fruit and vegetable consumption and smoking status using multiple logistic regression. RESULTS: The prevalence of multimorbidity was 61.2% (95% CI 57.7-64.7). Multimorbidity was independently associated with being female (P < 0.001) and severe/profound ID (P = 0.004). Increasing age was of borderline significance (P = 0.06). Individuals who were physically inactive or sedentary were more likely to be multimorbid, independent of ability to walk, age, gender, severity of ID, ethnicity and socio-economic status (adjusted OR = 1.91; 95% CI 1.23-2.97; P = 0.004 and OR = 1.98; 95% CI 1.42-2.77; P < 0.001). After excluding probable life-long conditions (autism spectrum conditions, attention deficit hyperactivity disorders, epilepsy, cerebral palsy and other paralytic syndromes) as contributing comorbidities, the effect of sedentary behaviour, but not physical activity, remained (P = 0.004). We did not observe a relationship between multimorbidity, fruit and vegetable consumption and smoking status. CONCLUSIONS: Multimorbidity presents a significant burden to people with ID. Individuals who were physically inactive or sedentary were more likely to be multimorbid, but further work is recommended to explore the relationship between multimorbidity and lifestyle factors using standardised objective measures.