Strategy for improved characterization of human metabolic phenotypes using a COmbined Multi-block Principal components Analysis with Statistical Spectroscopy (COMPASS).

MOTIVATION: Large-scale population omics data can provide insight into associations between gene-environment interactions and disease. However, existing dimension reduction modelling techniques are often inefficient for extracting detailed information from these complex datasets. RESULTS: Here, we present an interactive software pipeline for exploratory analyses of population-based nuclear magnetic resonance spectral data using a COmbined Multi-block Principal components Analysis with Statistical Spectroscopy (COMPASS) within the R-library hastaLaVista framework. Principal component analysis models are generated for a sequential series of spectral regions (blocks) to provide more granular detail defining sub-populations within the dataset. Molecular identification of key differentiating signals is subsequently achieved by implementing Statistical TOtal Correlation SpectroscopY on the full spectral data to define feature patterns. Finally, the distributions of cross-correlation of the reference patterns across the spectral dataset are used to provide population statistics for identifying underlying features arising from drug intake, latent diseases and diet. The COMPASS method thus provides an efficient semi-automated approach for screening population datasets. AVAILABILITY AND IMPLEMENTATION: Source code is available at https://github.com/cheminfo/COMPASS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Differential diagnosis of a thyroid mass, facial malar rash and ptosis on the flora in the primavera by Sandro Botticelli (1445-1510).

PURPOSE: The Primavera is considered amongst the greatest and controversial artistic masterpieces worldwide painted by renaissance artist Sandro Botticelli. The aim was to identify any underlying medical foundations for the painting. METHODS: Observational study. RESULTS: The painting reveals, a 'butterfly' malar rash, bilateral ptosis and a clear neck swelling consistent with a goitre in the figure of Flora. This could be explained by concomitant Graves' disease and systemic lupus erythematosus, or other presentations of multiple autoimmune syndrome. CONCLUSION: These findings highlight the likely presentation of the earliest pictorial depictions of thyroid disease with systemic lupus erythematosus and emphasize the exactitude of depiction demonstrated by Botticelli in renaissance era.

Endoscopic Interventions in the Treatment of Obesity and Diabetes.

Obesity is a global health problem which is on the rise and is strongly associated with the development of type 2 diabetes and other comorbidities. Bariatric surgery is now an established treatment for both these conditions, leading to impressive results in weight loss and glycemic control. More recently, we have seen the development of various endoscopic devices as potential alternatives or adjuncts to bariatric surgery. In this state-of-the-art review, we outline the current landscape of endoscopic treatments available for the management of both obesity and diabetes, including the clinical evidence supporting their use, efficacy, safety, and potential mechanisms of action.

Hypothyroidism in the "Arnolfini Portrait" (1434) by Jan Van Eyck (1390-1441).

BACKGROUND: The Arnolfini portrait painted by Jan van Eyck in 1434 remains one of the most puzzling yet alluring paintings of prerenaissance western art. PURPOSE: The painting is renowned for its exactitude in brush strokes, textures and the distinctive morphology of the main character Arnolfini. The nature of these requires pathological consideration. METHODS: Diagnostic and pathological analysis of the painting. RESULTS: A number of pathological abnormalities are noted in the face of the main character including loss of outer third of the eyebrow (Sign of Hertoghe), bilateral ptosis and melasma of the forehead. These together support a diagnosis of hypothyroidism. CONCLUSIONS: This novel diagnosis offers an additional perspective to this enigmatic portrait, and can add to the comprehension of the method, origin and pathological associations of this prominent painting from a genius artist.

The evolution of robotic surgery: surgical and anaesthetic aspects.

Robotic surgery pushes the frontiers of innovation in healthcare technology towards improved clinical outcomes. We discuss the evolution to five generations of robotic surgical platforms including stereotactic, endoscopic, bioinspired, microbots on the millimetre scale, and the future development of autonomous systems. We examine the challenges, obstacles and limitations of robotic surgery and its future potential including integrated real-time anatomical and immune-histological imaging and data assimilation with improved visualisation, haptic feedback and robot-surgeon interactivity. We consider current evidence, cost-effectiveness and the learning curve in relation to the surgical and anaesthetic journey, and what is required to continue to realise improvements in surgical operative care. The innovative impact of this technology holds the potential to achieve transformative clinical improvements. However, despite over 30 yr of incremental advances it remains formative in its innovative disruption.

Anastomotic leaks can be detected within 5 days following ileorectal anastomosis: a case-controlled study in patients with familial adenomatous polyposis.

AIM: To determine the earliest time point at which anastomotic leaks can be detected in patients undergoing total colectomy with primary ileorectal anastomosis for familial adenomatous polyposis. METHOD: This was a case-controlled study of 10 anastomotic leak patients vs 20 controls following laparoscopic total colectomy with ileorectal anastomosis for familial adenomatous polyposis (from 96 consecutive patients between 2006 and 2013). Panel time-series data regression was performed using a double subscript structure to include both variables. A generalized least squares multivariate approach was applied in a random effects setting to calculate correlations for observations, with anastomotic leak being the dependent variable. Univariate and multivariate regression calculations were then performed according to individual observations at each recorded time point. Time-series analysis was used to determine when a variable became significant in the leak group. RESULTS: Multivariate analysis identified a significant difference between leak and control groups in mean heart rate (P < 0.001), mean respiratory rate (P = 0.017) and mean urine output (P = 0.001). Time-point analysis showed that heart rate was significantly different between leak and control groups at postoperative day 4.25. Multivariate analysis identified a significant difference between groups in alanine transaminase (P = 0.006), bilirubin (P = 0.008), creatinine (P = 0.001), haemoglobin (P < 0.001) and urea (P = 0.007). There were no differences between groups with regard to markers of inflammation such as albumin, white blood cell count, neutrophil count and C-reactive protein. CONCLUSION: Anastomotic leaks can be detected early (within 4.5 days of surgery) through changes in physiological, blood test and observational parameters, providing an opportunity for early intervention in these patients to salvage the anastomosis.

Network meta-analysis of protocol-driven care and laparoscopic surgery for colorectal cancer.

BACKGROUND: Laparoscopic approaches and standardized recovery protocols have reduced morbidity following colorectal cancer surgery. As the optimal regimen remains inconclusive, a network meta-analysis was undertaken of treatments for the development of postoperative complications and mortality. METHODS: MEDLINE, Embase, trial registries and related reviews were searched for randomized trials comparing laparoscopic and open surgery within protocol-driven or conventional perioperative care for colorectal cancer resection, with complications as a defined endpoint. Relative odds ratios (ORs) for postoperative complications and mortality were estimated for aggregated data. RESULTS: Forty trials reporting on 11 516 randomized patients were included with the network. Open surgery within conventional perioperative care was the index for comparison. The OR relating to complications was 0·77 (95 per cent c.i. 0·65 to 0·91) for laparoscopic surgery within conventional care, 0·69 (0·48 to 0·99) for open surgery within protocol-driven care, and 0·43 (0·28 to 0·67) for laparoscopic surgery within protocol-driven care. Sensitivity analyses excluding trials of low rectal cancer and those with a high risk of bias did not affect the treatment estimates. Meta-analyses demonstrated that mortality risk was unaffected by perioperative strategy. CONCLUSION: Laparoscopic surgery combined with protocol-driven care reduces colorectal cancer surgery complications, but not mortality. The reduction in complications with protocol-driven care is greater for open surgery than for laparoscopic approaches. Registration number: CRD42015017850 (https://www.crd.york.ac.uk/PROSPERO).

Metabolic phenotype-microRNA data fusion analysis of the systemic consequences of Roux-en-Y gastric bypass surgery.

BACKGROUND/OBJECTIVES: Bariatric surgery offers sustained marked weight loss and often remission of type 2 diabetes, yet the mechanisms of establishment of these health benefits are not clear. SUBJECTS/METHODS: We mapped the coordinated systemic responses of gut hormones, the circulating miRNAome and the metabolome in a rat model of Roux-en-Y gastric bypass (RYGB) surgery. RESULTS: The response of circulating microRNAs (miRNAs) to RYGB was striking and selective. Analysis of 14 significantly altered circulating miRNAs within a pathway context was suggestive of modulation of signaling pathways including G protein signaling, neurodegeneration, inflammation, and growth and apoptosis responses. Concomitant alterations in the metabolome indicated increased glucose transport, accelerated glycolysis and inhibited gluconeogenesis in the liver. Of particular significance, we show significantly decreased circulating miRNA-122 levels and a more modest decline in hepatic levels, following surgery. In mechanistic studies, manipulation of miRNA-122 levels in a cell model induced changes in the activity of key enzymes involved in hepatic energy metabolism, glucose transport, glycolysis, tricarboxylic acid cycle, pentose phosphate shunt, fatty-acid oxidation and gluconeogenesis, consistent with the findings of the in vivo surgery-mediated responses, indicating the powerful homeostatic activity of the miRNAs. CONCLUSIONS: The close association between energy metabolism, neuronal signaling and gut microbial metabolites derived from the circulating miRNA, plasma, urine and liver metabolite and gut hormone correlations further supports an enhanced gut-brain signaling, which we suggest is hormonally mediated by both traditional gut hormones and miRNAs. This transomic approach to map the crosstalk between the circulating miRNAome and metabolome offers opportunities to understand complex systems biology within a disease and interventional treatment setting.

Neuropsychological assessment as a predictor of weight loss in obese adolescents.

BACKGROUND: Obese individuals are known to be more impulsive than their normal-weight counterparts. Impulsivity has been postulated to be a predictor of weight loss. DESIGN: A pre-post study was designed to determine for the first time whether impulsivity changed with weight loss during a lifestyle and physical activity intervention programme lasting 2-8 weeks. SUBJECTS: Fifty-three obese adolescents with a body mass index (BMI) of 33.75 ± 7.9 attending a residential camp were tested and compared at baseline with 50 non-obese adolescents with a mean BMI of 20.6 ± 2.3. MEASUREMENTS: Inhibitory control was measured with the CANTAB (Cambridge Cognition, Cambridge, UK) Stop Signal Task. MATLAB (The Mathswork Inc., Natick, MA, USA) was used to measure the temporal discounting constant. RESULTS: The obese group was more impulsive than the normal weight adolescents. BMI reduced significantly from 33.76 kg m(-2) to 30.93 kg m(-2) after completing camp. The stop signal reaction time (SSRT) decreased from 225.38 ± 94.22 to 173.76 ± 107.05 ms (n=47, P=0.0001). A reduction in inhibitory control during camp was predictive of those who showed the greatest reduction in BMI (Wilks' Lambda=0.9, F(1,50)=4.85, P=0.034). The number of weeks in camp (Wilks' Lambda=0.83, F(1,50)=9.826, P=0.003) and the age of the adolescents (Wilks' Lambda=0.87, F(1,50)=5.98, P=0.02) were significantly associated with a reduction in inhibitory control as measured by the SSRT. A longer stay in camp was associated with a greater reduction in SSRT (B=25.45, t=2.02, P=0.05). Increasing age had a significant moderating role in the reduction of inhibitory control (B=-0.3, t=-0.034, P=0.05). Temporal discounting for monetary reward also fell significantly during camp. CONCLUSION: This study highlights the potential to identify those who are obese by using an easy-to-measure psychometric test. Furthermore, it is the first study to report a reduction in impulsivity and an improvement in well-being as part of a government-approved residential camp for obese adolescents. The potential mechanisms for change in impulsivity with weight are discussed.

Off-pump versus on-pump revascularization in females: a meta-analysis of observational studies.

BACKGROUND: Coronary revascularization in female patients presents several challenges, including smaller target vessels and smaller conduits. Furthermore, late presentation and more co-morbidities than males may increase complication rates. The aim of this study was to assess whether off-pump coronary artery bypass (OPCAB) improves outcomes when compared to on-pump coronary artery bypass (ONCAB) in the female population. METHODS: A systematic literature review identified six observational studies, incorporating 23313 patients (n=9596 OPCAB, 13717 ONCAB). These were meta-analyzed using random effects modeling. Heterogeneity, subgroup analysis, quality scoring and publication bias were assessed. The primary endpoints were 30-day mortality and major cardiac, respiratory and renal complications. Secondary endpoints were the number of grafts per patient. RESULTS: No statistically significant difference was observed in 30-day mortality between the OPCAB and ONCAB groups (4.8% vs. 0.7%; OR 0.96; 95% CI [0.41, 2.24], p=0.92). Significant inter-study heterogeneity was also present (I2=94%) and was not explained by study size or quality. Peri-operative myocardial infarction (OR 0.65; 95% CI [0.51, 0.84], p=0.0009) was significantly lower with OPCAB without significant heterogeneity; however, OPCAB did not significantly alter other morbidity outcomes. OPCAB was associated with a trend towards fewer grafts per patient than ONCAB. CONCLUSIONS: OPCAB is a safe alternative to ONCAB in the surgical revascularisation of female patients and may reduce post-operative myocardial infarction (MI). However, this does not translate into a reduction in 30-day mortality and OPCAB does not significantly improve other cardiovascular, renal or neurological outcomes. Late outcome data remains lacking and a well-structured, randomized trial is required to answer vital questions regarding the effect of OPCAB on women in the long-term.

Does off-pump coronary revascularization reduce mortality in re-operative coronary artery surgery? A meta-analysis of observational studies.

BACKGROUND: Re-operative coronary artery bypass grafting (CABG) is a challenging operation that is often performed in a high-risk patient group. Avoiding cardiopulmonary bypass (CPB) in these patients is hypothesised to be advantageous due to the reduced invasiveness and physiological stress of off-pump coronary artery bypass grafting (OPCAB). The aims of this study were to assess whether OPCAB may improve outcomes in patients undergoing re-operative CABG. METHODS: Twelve studies, incorporating 3471 patients, were identified by systematic literature review. These were meta-analysed using random-effects modelling. Primary endpoints were 30-day and mid-term mortality. Secondary endpoints were completeness of revascularization, mean number of grafts per patient and the effect of intra-operative conversion on mortality. RESULTS: A significantly lower rate of 30-day mortality was observed with OPCAB (OR 0.51, 95% CI [0.35, 0.74]), however, no difference was demonstrated in mid-term mortality. Significantly less complete revascularization and mean number of grafts per patient were observed in the OPCAB group. Meta-regression revealed no change in 30-day mortality when the effect of conversion from one technique to the other was assessed. CONCLUSIONS: Off-pump techniques may reduce early mortality in selected patients undergoing re-operative CABG; however, this does not persist into mid-term follow-up. OPCAB may also lead to intra-operative conversion and, although this did not affect outcomes in this study, these results are constrained by the limited data available. Furthermore, OPCAB may increase target vessel revascularization and, consequently, incomplete revascularization which, whilst not reflected in the short-term outcomes, requires longer-term follow-up in order to be fully assessed.

Safety of training and assessment in operating theatres--a systematic review and meta-analysis.

OBJECTIVE: Procedural outcomes can be used to assess the performance of specialists and trainees. This article establishes a systematic evidence base for the safety of training in the operating theatre. It also explores the possibility of using early, intermediate and late procedural outcomes of cardiac surgical operations to evaluate the performance of the clinicians and the healthcare system. METHODS: Medline, EMBASE and PsycINFO databases were searched. Comparative studies evaluating quality indicators of cardiac surgical procedures (coronary artery bypass grafting (CABG) and valve surgery) were included. guidelines from the preferred reporting items for systematic reviews and meta-analyses (PRISMA) were used. RESULTS: Fourteen studies met the inclusion criteria. For CABG, meta-analysis of outcomes did not show any significant differences between the technical and non-technical skills of trainees versus specialists apart from bypass time (less for specialists) and intensive care unit (ICU) length of stay (less for trainees). Studies reporting outcomes on valve surgery also did not report any statistically significant differences amongst the outcomes. CONCLUSION: This systematic review did not discern any significant differences between the procedural outcomes of trainees and specialists, which indicates that trainees are safe to operate under senior supervision. In addition, this article recommends that various procedural outcomes can be used to evaluate the performance of clinicians and healthcare systems. Prospective studies need to be performed, taking into account the specific contribution of trainees and specialists during the procedure. This will give a clearer indication of safety and performance of trainees and specialists in the operating theatre.

Overview of trials on artificial intelligence algorithms in breast cancer screening - A roadmap for international evaluation and implementation.

Accumulating evidence from retrospective studies demonstrate at least non-inferior performance when using AI algorithms with different strategies versus double-reading in mammography screening. In addition, AI algorithms for mammography screening can reduce work load by moving to single human reading. Prospective trials are essential to avoid unintended adverse consequences before incorporation of AI algorithms into UK's National Health Service (NHS) Breast Screening Programme (BSP). A stakeholders' meeting was organized in Newnham College, Cambridge, UK to undertake a review of the current evidence to enable consensus discussion on next steps required before implementation into a screening programme. It was concluded that a multicentre multivendor testing platform study with opt-out consent is preferred. AI thresholds from different vendors should be determined while maintaining non-inferior screening performance results, particularly ensuring recall rates are not increased. Automatic recall of cases using an agreed high sensitivity AI score versus automatic rule out with a low AI score set at a high sensitivity could be used. A human reader should still be involved in decision making with AI-only recalls requiring human arbitration. Standalone AI algorithms used without prompting maintain unbiased screening reading performance, but reading with prompts should be tested prospectively and ideally provided for arbitration.

Trends and associated factors for Covid-19 hospitalisation and fatality risk in 2.3 million adults in England.

The Covid-19 mortality rate varies between countries and over time but the extent to which this is explained by the underlying risk in those infected is unclear. Using data on all adults in England with a positive Covid-19 test between 1st October 2020 and 30th April 2021 linked to clinical records, we examined trends and risk factors for hospital admission and mortality. Of 2,311,282 people included in the study, 164,046 (7.1%) were admitted and 53,156 (2.3%) died within 28 days of a positive Covid-19 test. We found significant variation in the case hospitalisation and mortality risk over time, which remained after accounting for the underlying risk of those infected. Older age groups, males, those resident in areas of greater socioeconomic deprivation, and those with obesity had higher odds of admission and death. People with severe mental illness and learning disability had the highest odds of admission and death. Our findings highlight both the role of external factors in Covid-19 admission and mortality risk and the need for more proactive care in the most vulnerable groups.

Management of the left subclavian artery during endovascular stent grafting for traumatic aortic injury - a systematic review.

OBJECTIVES AND DESIGN: Traumatic thoracic aortic injuries are serious and may be associated with high morbidity and mortality. Endovascular stent grafting is now an established treatment option which often requires proximal landing zone extension through left subclavian artery (LSA) origin coverage. This in turn can lead to downstream ischaemic complications which may be lessened by LSA revascularisation. This study investigates the consequence of LSA coverage and potential benefit of revascularisation. MATERIALS AND METHODS: Systematic literature review of studies between 1997 and 2010 identified 94 studies incorporating 1704 patients. Chronological trends in LSA management practice for trauma were sought. Designated outcomes of interest were prevalences of left arm ischaemia, stroke, spinal cord ischaemia, endoleak, stent migration, need for additional procedure and mortality. These outcomes were compared in patients with and without LSA coverage (taking account of the degree of coverage). The impact of revascularisation on these outcomes was also explored. Statistical analysis included examination with Chi-Square or Fisher's tests as appropriate. RESULTS: Isolated total LSA coverage without revascularisation increases the prevalence of left arm ischaemia [prevalence of 4.06% versus 0.0% (p < 0.001)]; stroke [prevalence of 1.19% versus 0.23% (p = 0.025)]; and need for additional procedure [prevalence of 2.86% versus 0.86% (p = 0.004). In contrast there were no reported cases of stroke, spinal cord ischaemia, endoleak, stent migration or mortality when the LSA origin was only partially covered. When the LSA territory was revascularised, again no cases of left arm ischaemia, stroke, spinal cord ischaemia, endoleak, or mortality were reported. CONCLUSION: Current evidence suggests that LSA coverage in patients undergoing endovascular stent grafting of the thoracic aorta for trauma should be avoided where possible to avoid ensuing downstream ischaemic complications. When coverage is anatomically necessary, partial coverage is better than complete in terms of avoiding these complications and revascularisation may be considered, however these decisions must be made in the context of the individual patient scenario.

Obese patients and robotic colorectal surgery: systematic review and meta-analysis.

BACKGROUND: Obesity is a major health problem, demonstrated to double the risk of colorectal cancer. The benefits of robotic colorectal surgery in obese patients remain largely unknown. This meta-analysis evaluated the clinical and pathological outcomes of robotic colorectal surgery in obese and non-obese patients. METHODS: MEDLINE, Embase, Global Health, Healthcare Management Information Consortium (HMIC) and Midwives Information and Resources Service (MIDIRS) databases were searched on 1 August 2018 with no language restriction. Meta-analysis was performed according to PRISMA guidelines. Obese patients (BMI 30 kg/m2 or above) undergoing robotic colorectal cancer resections were compared with non-obese patients. Included outcome measures were: operative outcomes (duration of surgery, conversion to laparotomy, blood loss), postoperative complications, hospital length of stay and pathological outcomes (number of retrieved lymph nodes, positive circumferential resection margins and length of distal margin in rectal surgery). RESULTS: A total of 131 full-text articles were reviewed, of which 12 met the inclusion criteria and were included in the final analysis. There were 3166 non-obese and 1420 obese patients. A longer duration of surgery was documented in obese compared with non-obese patients (weighted mean difference -21·99 (95 per cent c.i. -31·52 to -12·46) min; P < 0·001). Obese patients had a higher rate of conversion to laparotomy than non-obese patients (odds ratio 1·99, 95 per cent c.i. 1·54 to 2·56; P < 0·001). Blood loss, postoperative complications, length of hospital stay and pathological outcomes were not significantly different in obese and non-obese patients. CONCLUSION: Robotic surgery in obese patients results in a significantly longer duration of surgery and higher conversion rates than in non-obese patients. Further studies should focus on better stratification of the obese population with colorectal disease as candidates for robotic procedures.

ANTECEDENTES: La obesidad es un grave problema de salud; se ha demostrado que duplica el riesgo de cáncer colorrectal (colorectal cáncer, CRC). Los beneficios de la cirugía robótica colorrectal en pacientes obesos siguen siendo en gran medida desconocidos. Este metaanálisis evalúa los resultados clínicos y patológicos en la cirugía colorrectal robótica en pacientes obesos y no obesos. MÉTODOS: Se realizaron búsquedas bibliográficas en las bases de datos MEDLINE, EMBASE, Global Health, HMIC y MIDIRS el 1 de agosto de 2018 sin restricción de idioma. Este metaanálisis se realizó de acuerdo con las directrices PRISMA. Los pacientes obesos (IMC ≥ 30 kg/m2 ) sometidos a resecciones robóticas de CRC se compararon con pacientes no obesos. Las medidas de resultado incluidas fueron: resultados operatorios (duración de la operación, conversión a laparotomía, pérdidas hemáticas), complicaciones postoperatorias, duración de la estancia hospitalaria y resultados patológicos (número de ganglios linfáticos identificados, márgenes de resección circunferencial positivos y longitud del margen distal en la cirugía del cáncer de recto). RESULTADOS: Se revisaron 131 artículos de texto completo, de ellos, 12 artículos cumplieron los criterios de inclusión y se incluyeron en el análisis final. Hubo 3.166 pacientes no obesos y 1.420 pacientes obesos. Se registró un mayor tiempo operatorio en pacientes obesos en comparación con pacientes no obesos (diferencia media ponderada -21,989; i.c. del 95% −31,516 a 12,461, P < 0,005). Los pacientes obesos tuvieron una tasa de conversión más alta que los pacientes no obesos (i.c. del 95% 1,541 a 2,565, P < 0,005). Las pérdidas hemáticas, las complicaciones postoperatorias y la duración de la estancia hospitalaria no mostraron diferencias significativas. No hubo diferencias significativas en los resultados patológicos entre pacientes obesos y no obesos. CONCLUSIÓN: La cirugía robótica en pacientes obesos se asocia con un tiempo quirúrgico significativamente mayor y tasas de conversión más altas que en pacientes no obesos. Otros estudios deberían centrarse en estratificar mejor a los pacientes obesos con enfermedad colorrectal como candidatos a cirugía robótica.