Real-time assessment of learning curve for robot-assisted laparoscopic prostatectomy.

INTRODUCTION: The learning curves analysed to date for robot-assisted laparoscopic prostatectomy are based on arbitrary cut-offs of the total cases. METHODS: We analysed a large dataset of robot-assisted laparoscopic prostatectomies from a single centre between 2008 and 2019 for assessment of the learning curve for perioperative outcomes with respect to time and individual cases. RESULTS: A total of 1,406 patients were evaluated, with mean operative time 198.08 minutes and mean console time 161.05 minutes. A plot of operative time and console time showed an initial decline followed by a near-constant phase. The inflection points were detected at 1,398 days (308th case) for operative time and 1,470 days (324th case) for console time, with a declining trend of 8.83 minutes and 7.07 minutes, respectively, per quarter-year (p<0.001). Mean estimated blood loss showed a 70.04% reduction between the start (214.76ml) and end (64.35ml) (p<0.001). The complication rate did not vary with respect to time (p=0.188) or the number of procedures (p=0.354). There was insufficient evidence to claim that the number of operations (p=0.326), D'Amico classification (p=0.114 for intermediate versus low; p=0.158 for high versus low) or time (p=0.114) was associated with the odds of positive surgical margins. CONCLUSIONS: It takes about 300 cases and nearly 4 years to standardise operative and console times, with a requirement of around 80 cases per annum for a single surgical team in the initial years to optimise the outcomes of robot-assisted laparoscopic prostatectomy.

Dietary fat and obesity as modulators of breast cancer risk: Focus on DNA methylation.

Breast cancer (BC) is the most common cancer and second leading cause of cancer mortality in women worldwide. Validated biomarkers enhance efforts for early detection and treatment, which reduce the risk of mortality. Epigenetic signatures have been suggested as good biomarkers for early detection, prognosis and targeted therapy of BC. Here, we highlight studies documenting the modifying effects of dietary fatty acids and obesity on BC biomarkers associated with DNA methylation. We focus our analysis on changes elicited in writers of DNA methylation (i.e., DNA methyltransferases), global DNA methylation and gene-specific DNA methylation. To provide context, we precede this discussion with a review of the available evidence for an association between BC incidence and both dietary fat consumption and obesity. We also include a review of well-vetted BC biomarkers related to cytosine-guanine dinucleotides methylation and how they influence BC risk, prognosis, tumour characteristics and response to treatment. LINKED ARTICLES: This article is part of a themed section on The Pharmacology of Nutraceuticals. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.6/issuetoc.

Discriminating movements of liquid and gas in the rabbit colon with impedance manometry.

BACKGROUND: High-resolution impedance manometry is a technique that is well established in esophageal motility studies for relating motor patterns to bolus flow. The use of this technique in the colon has not been established. METHODS: In isolated segments of rabbit proximal colon, we recorded motor patterns and the movement of liquid or gas boluses with a high-resolution impedance manometry catheter. These detected movements were compared to video recorded changes in gut diameter. Using the characteristic shapes of the admittance (inverse of impedance) and pressure signals associated with gas or liquid flow we developed a computational algorithm for the automated detection of these events. KEY RESULTS: Propagating contractions detected by video were also recorded by manometry and impedance. Neither pressure nor admittance signals alone could distinguish between liquid and gas transit, however the precise relationship between admittance and pressure signals during bolus flow could. Training our computational algorithm upon these characteristic shapes yielded a detection accuracy of 87.7% when compared to gas or liquid bolus events detected by manual analysis. CONCLUSIONS & INFERENCES: Characterizing the relationship between both admittance and pressure recorded with high-resolution impedance manometry can not only help in detecting luminal transit in real time, but also distinguishes between liquid and gaseous content. This technique holds promise for determining the propulsive nature of human colonic motor patterns.

Motility patterns in mouse colon: gastrointestinal dysfunction induced by anticancer chemotherapy.

Colon cancer is a leading cause of cancer-related death in humans. 5-Fluorouracil (5-FU), a major chemotherapy treatment, has been used for decades to fight numerous types of cancers, including breast, colon, and head and neck carcinomas. Unfortunately, a large proportion of patients treated with 5-FU develop toxicities that include diarrhea, mucositis, neutropenia, and vomiting. While the side effects of 5-FU are well known, the mechanisms underlying the induction of these unpleasant symptoms are poorly understood. The study by McQuade et al. in this issue of Neurogastroenterology & Motility provides important new potential explanations for the gastrointestinal (GI) dysfunction induced by 5-FU. These researchers carefully investigated an overlooked research area in which the symptoms of GI-motility dysfunction maybe due to an effect on the enteric nervous system. McQuade et al. delivered 5-FU treatment to mice and discovered an initial increase in GI transit (associated with acute intestinal inflammation), followed by a slowing in transit. Major differences were noted in characteristics of colonic migrating motor complexes. These effects maybe causally related to deficits in enteric ganglia or neurotransmission. Their study identified specific neurochemical classes of neurons in the myenteric plexus most affected by 5-FU. This is the first study to provide evidence that the functional intrinsic neural pathways within the enteric nervous system are likely impaired by 5-FU, leading to colonic dysmotility. This review will describe major patterns of motor activity in isolated whole mouse colon and how these patterns are modified by anticancer chemotherapy.

High-resolution colonic motility recordings in vivo compared with ex vivo recordings after colectomy, in patients with slow transit constipation.

BACKGROUND: The pathogenesis of slow transit constipation (STC) remains poorly understood, with intrinsic and extrinsic abnormalities implicated. Here, we present high-resolution colonic manometry recordings from four STC patients recorded before total colectomy, and subsequently, ex vivo, after excision. METHODS: In four female, treatment-resistant STC patients (median age 35.5 years), a fiber-optic manometry catheter (72 sensors spaced at 1 cm intervals) was placed with the aid of a colonoscope, to the mid-transverse colon. Colonic manometry was recorded 2 h before and after a meal. After the colectomy, ex vivo colonic manometry was recorded in an organ bath. Ex vivo recordings were also made from colons from 4 patients (2 male; median age 67.5 years) undergoing anterior resection for nonobstructive carcinoma ('control' tissue). KEY RESULTS: A large increase in 'short single propagating contractions' was recorded in STC colon ex vivo compared to in vivo (ex vivo 61.3 ± 32.7 vs in vivo 2.5 ± 5/h). In STC patients, in vivo, the dominant frequency of contractile activity was 2-3 cycle per minute (cpm), whereas 1-cpm short-single propagating contractions dominated ex vivo. This same 1-cpm frequency was also dominant in control colons ex vivo. CONCLUSIONS & INFERENCES: In comparison to control adults, the colon of STC patients demonstrates significantly less propagating motor activity. However, once the STC colon is excised from the body it demonstrates a regular and similar frequency of propagating activity to control tissue. This paper provides interesting insights into the control of colonic motor patterns.

Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. Recently, a specific highly activated T helper cell subset, follicular helper T (Tfh) cell, has emerged as a key immunoregulator of germinal center (GC) formation and high-affinity antibody production. To identify the pathophysiological role of Tfh cells in SLE patients, we compared the phenotypic and functional properties of circulating Tfh-like cells in lupus patients to GC-Tfh cells, and correlated the percentage of Tfh-like cells with autoantibody production and SLE disease activity. METHODS: Peripheral blood was collected from 29 lupus patients and 25 healthy controls. Tonsils were obtained surgically from non-SLE controls and used as a source of GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, PD-1 and BTLA) via flow cytometry. IL-21 expression levels from Tfh cells were measured by real-time PCR and intracellular staining. The function of Tfh cells was carried out by co-culture of Tfh cells and autologous B cells in vitro. IgG in the culture supernatant was detected by ELISA. RESULTS: The frequency of circulating Tfh-like cells was significantly increased in SLE patients compared to healthy controls (p < 0.05). The Tfh-like cells not only display similar phenotypes and signature cytokines with GC-Tfh cells, but also are capable of driving B cells to differentiate into IgG-secreting plasma cells in vitro. In addition, the frequency of Tfh-like cells correlated positively with the percentage of circulating plasmablasts, levels of serum anti-dsDNA antibodies and ANA. CONCLUSION: The accumulated circulating Tfh-like cells in lupus patients share phenotypic and functional properties with GC-Tfh cells. Tfh-like cells may serve as perpetuators in the pathogenesis of SLE by enhancing the self-reactive B cell clones to further differentiate into auto antibody-producing plasmablasts, and ultimately cause autoimmunity.

Characterization of the natural history of extracellular matrix production in tissue-engineered vascular grafts during neovessel formation.

BACKGROUND: The extracellular matrix (ECM) is a critical determinant of neovessel integrity. MATERIALS AND METHODS: Thirty-six (polyglycolic acid + polycaprolactone and poly lactic acid) tissue-engineered vascular grafts seeded with syngeneic bone marrow mononuclear cells were implanted as inferior vena cava interposition grafts in C57BL/6 mice. Specimens were characterized using immunohistochemical staining and qPCR for representative ECM components in addition to matrix metalloproteinases (MMPs). Total collagen, elastin, and glycosaminoglycan (GAG) contents were determined. MMP activity was measured using zymography. RESULTS: Collagen production on histology demonstrated an initial increase in type III at 1 week followed by type I production at 2 weeks and type IV at 4 weeks. Gene expression of both type I and type III peaked at 2 weeks, whereas type IV continued to increase over the 4-week period. Histology demonstrated fibrillin-1 deposition at 1 week followed by elastin production at 4 weeks. Elastin gene expression significantly increased at 4 weeks, whereas fibrillin-1 decreased at 4 weeks. GAG demonstrated abundant production at each time point on histology. Gene expression of decorin significantly increased at 4 weeks, whereas versican decreased over time. Biochemical analysis showed that total collagen production was greatest at 2 weeks, and there was a significant increase in elastin and GAG production at 4 weeks. Histological characterization of MMPs showed abundant production of MMP-2 at each time point, while MMP-9 decreased over the 4-week period. Gene expression of MMP-2 significantly increased at 4 weeks, whereas MMP-9 significantly decreased at 4 weeks. CONCLUSIONS: ECM production during neovessel formation is characterized by early ECM deposition followed by extensive remodeling.

Insertion of six different supraglottic airway devices whilst wearing chemical, biological, radiation, nuclear-personal protective equipment: a manikin study.

Six different supraglottic airway devices: Combitube™, laryngeal mask airway, intubating laryngeal mask airway (Fastrach™), i-gel™, Laryngeal Tube™ and Pro-Seal™ laryngeal mask airway were assessed by 58 paramedic students for speed and ease of insertion in a manikin, whilst wearing either chemical, biological, radiation, nuclear-personal protective equipment (CBRN-PPE) or a standard uniform. All devices took significantly longer to insert when wearing CBRN-PPE compared with standard uniform (p < 0.001). In standard uniform, insertion time was shorter than 45 s in 90% of attempts for all devices except the Combitube, for which 90% of attempts were completed by 53 s. Whilst wearing CBRN-PPE the i-gel was the fastest device to insert with a mean (SD (95% CI)) insertion time of 19 (8 (17-21))s, p < 0.001, with the Combitube the slowest with mean (65 (23 (59-71))s. Wearing of CBRN-PPE has a negative impact on supraglottic airway insertion time.

Surgical management of vascular lesions of the head and neck: a review of 115 cases.

Vascular anomalies are amongst the most common congenital abnormalities observed in infants and children. Their occurrence in the head and neck region is a source of functional and aesthetic compromise. This article reviews the surgical management of 115 cases of vascular anomalies involving the head and neck area treated by the authors between 1998 and 2009. It discusses the diagnostic aids, treatment protocol and the results obtained. A new classification based on the anatomical location and depth of the lesion has been proposed. This allows guidelines for surgical ablation of the vascular lesions. The complications encountered are discussed. The use of external carotid artery control as opposed to pre-surgical embolization has proved effective and the technique is described. The location and extent of a vascular malformation should dictate the preoperative investigations, surgical procedure and subsequent outcome.

Isolated fracture of the superior orbital fissure.

We report a case of a patient with an isolated fracture of the superior orbital fissure and development of superior orbital fissure syndrome.

Feasibility of screening for Chlamydia trachomatis in young men attending an emergency department.

OBJECTIVE: To determine the feasibility of screening asymptomatic young men for genital Chlamydia trachomatis infection in a suburban emergency department setting. DESIGN: Prospective observational study. SETTING: Chase Farm Hospital Emergency Department in Enfield, North London. PARTICIPANTS: Asymptomatic sexually active men aged 16-24 years. METHODS: A convenience sample of men aged 16-24 years attending the emergency department was offered urine-based screening for Chlamydia at triage. Verbal consent was obtained and first pass urine specimens were tested using the strand displacement amplification technique. Participants were traced by their preferred method of contact in order to be offered treatment within 2 weeks of attendance at the emergency department. RESULTS: 67 men participated, 64 of whom were tested, 3 returning positive tests. The prevalence of Chlamydia in asymptomatic men attending the emergency department was 4.7%. CONCLUSION: Urine testing for genital C trachomatis in the emergency department can identify asymptomatic men in the community who may otherwise remain undetected. It is suggested that this is a worthwhile screening test to offer in the emergency department, providing follow-up for treatment can be arranged locally. There is no requirement for increased emergency department input into these patients over and above introducing them to the screening programme.

Rates and social patterning of household smoking and breastfeeding in contrasting European settings.

OBJECTIVE: To compare rates and social patterning of household smoking and breastfeeding in families with newborn infants in birth cohorts in Coventry, UK and Veria, North Greece. METHODS: Infants born in 1996 in Coventry, 1999 in Veria were recruited into birth cohort studies using similar methodologies. In Coventry recruitment was by family health visitor at the primary visit; in Veria, hospital-based paediatricians enrolled infants at the neonatal examination. Data were collected at the initial contact on household smoking, type of feeding, and household socio-demographic characteristics. Rates of initial breastfeeding and household smoking with 95% confidence intervals were estimated and breastfeeding and household smoking regressed on parental education and housing tenure in logistic regression models. RESULTS: Data were available on 2612 Coventry infants and 773 Veria infants. Rates of household smoking and breastfeeding were higher in Veria compared to Coventry. In Coventry, living in rented accommodation and lower maternal and paternal education were associated with household smoking and bottle feeding. Logistic regression models fitted on initiation of breastfeeding failed to show social patterning in Veria but more educated mothers showed a longer duration of breastfeeding. Only low paternal education was associated with household smoking after adjustment for maternal education and housing tenure. CONCLUSIONS: Smoking and breastfeeding are more prevalent among households with young infants in Veria compared with Coventry. The social patterning of health-related behaviours noted in Coventry is less marked in Veria. The relevance of these findings for public health interventions in the contrasting settings is discussed.

Parent reported home smoking bans and toddler (18-30 month) smoke exposure: a cross-sectional survey.

AIMS: To study the relation between the use of parent reported home smoking bans and smoke exposure among children aged 18-30 months. METHODS: A total of 309 smoking households with children aged 18-30 months, who were part of the Coventry Cohort study, consented to participate in this cross-sectional survey. RESULTS: Although parents in almost 88% of smoking households reported using harm reduction strategies to protect their toddlers from smoke exposure, only 13.9% reported smoking bans in the house. Mean log urinary cotinine:creatinine ratio was significantly lower for those children whose parents reported no smoking in the house (1.11, 95% CI 0.64 to 1.49) compared with none/less strict strategies (1.87, 95% CI 1.64 to 2.10). In linear regression models fitted on log cotinine:creatinine ratio, no smoking in the house was independently associated with a significant reduction in cotinine:creatinine ratio (B = -0.55, 95% CI -0.89 to -0.20) after adjusting for mother's and partner's average daily cigarette consumption, housing tenure, and overcrowding. The final model accounted for 44.3% of the variance. CONCLUSIONS: Not smoking in the house was associated with a reduction in mean urinary cotinine:creatinine ratio in children aged 18-30 months; the relation persisted after adjustment for levels of mother's and partner's daily cigarette consumption and sociodemographic factors. Results suggest that home smoking bans in this age group have a small but significant effect on smoke exposure independent of levels of parental tobacco consumption.

Parental smoking and passive smoking in infants: fathers matter too.

This study examines mothers' and fathers' smoking patterns in different kinds of smoking households, and assesses their relative contribution to infants' exposure to environmental tobacco smoke. It uses data from a cross-sectional survey of 314 smoking households (infants: mean age 10 weeks) in Coventry and Birmingham, England, examining reported tobacco consumption and objective measures of exposure: the study infant's urinary cotinine:creatinine ratios and their mother's salivary cotinine. The study shows that both mothers' and fathers' tobacco smoke make substantial contributions to infant exposure to tobacco smoke. Households were more likely to contain a smoking father than mother, with over two-thirds of households including a smoking father. In households where both parents smoke, fathers' tobacco consumption was found to be significantly higher than in households where only the father smokes. This suggests that the interaction between parents needs to be considered rather than focusing on mothers' or fathers' smoking behaviour in isolation. The implications for health promotion programmes are discussed, particularly the need to place more emphasis on tackling fathers' smoking. Currently, fathers' smoking receives far less research or health promotion attention than mothers' smoking. Protecting infants from fathers' as well as mothers' smoking is key to reducing environmental tobacco exposure in early infancy, when the risk of Sudden Infant Death is highest.

Interaction forces and morphology of a protein-resistant poly(ethylene glycol) layer.

The molecular interactions on a protein-resistant surface coated with low-molecular-weight poly(ethylene glycol) (PEG) copolymer brushes are investigated using the extended surface forces apparatus. The observed interaction force is predominantly repulsive and nearly elastic. The chains are extended with respect to the Flory radius, which is in agreement with qualitative predictions of scaling theory. Comparison with theory allows the determination of relevant quantities such as brush length and adsorbed mass. Based on these results, we propose a molecular model for the adsorbed copolymer morphology. Surface-force isotherms measured at high resolution allow distinctive structural forces to be detected, suggesting the existence of a weak equilibrium network between poly(ethylene glycol) and water--a finding in accordance with the remarkable solution properties of PEG. The occurrence of a fine structure is interpreted as a water-induced restriction of the polymer's conformational space. This restriction is highly relevant for the phenomenon of PEG protein resistance. Protein adsorption requires conformational transitions, both in the protein as well as in the PEG layer, which are energetically and kinetically unfavorable.

Treatment of peripheral sensorineural hearing loss: gene therapy.

Noise, chemicals and genetic defects are all common causes of irreversible hearing loss, which at present have no cure. Gene therapy may soon be utilized in both the protection and the treatment of these exogenous and endogenous sources of hearing loss. Gene therapy technology is rapidly developing and the inner ear is a particularly feasible model for gene therapy. This review outlines our current understanding of the mechanisms behind deafness and prospects for treatment, discusses the inner ear model in detail and reviews the efforts that have been made in inner ear gene therapy. Finally, the proposed next steps will be discussed. The viral mediated delivery of neurotrophins and antioxidants offers imminent promise in preventing and treating exogenous hearing loss and improving cochlear implant therapy.

Sudden unexpected death in infancy and socioeconomic status: a systematic review.

This paper aimed to systematically review observational studies documenting the relation between sudden unexpected death in infancy and socioeconomic status. A search of two electronic databases (Medline 1966 to November 2002; Embase 1981 to November 2002) yielded 52 case-control or cohort studies meeting the inclusion criteria. An increased risk of sudden unexpected death in infancy was reported in 51 studies and 32 of 33 studies reporting graded measures of socioeconomic status showed a dose-response relation of sudden death with socioeconomic status. Of the 10 studies in which adjustment was made for maternal smoking, socioeconomic status retained an independent effect on infant death in nine. The effect of socioeconomic status was also independent of birth weight in 10 of 11 studies and independent of sleeping position in two. The included studies reported a significant association of socioeconomic status with sudden unexpected death in infancy with risk of infant death increasing with greater exposure to adverse social circumstances. The findings support a significant role for adverse social circumstances in the pathways to sudden unexpected death in infancy.