Pragmatic staging of oesophageal cancer using decision theory involving selective endoscopic ultrasonography, PET and laparoscopy.

BACKGROUND: Following CT, guidelines for staging oesophageal and gastro-oesophageal junction (GOJ) cancer recommend endoscopic ultrasonography (EUS), PET-CT and laparoscopy for T3-T4 GOJ tumours. These recommendations are based on generic utilities, but it is unclear whether the test risk outweighs the potential benefit for some patients. This study sought to quantify investigation risks, benefits and utilities, in order to develop pragmatic, personalized staging recommendations. METHODS: All patients with a histological diagnosis of oesophageal or GOJ cancer staged between May 2006 and July 2013 comprised a development set; those staged from July 2013 to July 2014 formed the prospective validation set. Probability thresholds of altering management were calculated and predictive factors identified. Algorithms and models (decision tree analysis, logistic regression, artificial neural networks) were validated internally and independently. RESULTS: Some 953 patients were staged following CT, by [(18) F]fluorodeoxyglucose PET-CT (918), EUS (798) and laparoscopy (458). Of these patients, 829 comprised the development set (800 PET-CT, 698 EUS, 397 laparoscopy) and 124 the validation set (118 PET-CT, 100 EUS, 61 laparoscopy). EUS utility in the 71.8 per cent of patients with T2-T4a disease on CT was minimal (0.4 per cent), its risk exceeding benefit. EUS was moderately accurate for pT1 N0 disease. A number of factors predicted metastases on PET-CT and laparoscopy, although none could inform an algorithm. PET-CT altered management in 23.0 per cent, and laparoscopy in 7.1 per cent, including those with T2 and distal oesophageal tumours. CONCLUSION: Although EUS provided additional information on T and N category, its risk outweighed potential benefit in patients with T2-T4a disease on CT. Laparoscopy seemed justified for distal oesophageal tumours of T2 or greater.

Comparison of static and dynamic in vitro digestibility and bioaccessibility of palm-based emulsions and correlation to a human study: effects of triacylglycerol crystallinity.

The static and dynamic TIM-1 in vitro digestibility of similarly sized Span 60 o/w emulsions containing either liquid palm olein droplets (PO) or palm stearin (PS) droplets tempered to contain different levels of crystallinity (i.e., PS-SE (maximum), PS-SE-INT (intermediate), and PS-LE (undercooled)) were explored. Static in vitro digestion experiments included particle size analysis, and emulsion digestibility and bioaccessibility were compared between the static and dynamic models, respectively. ß-carotene (BC, 0.1 wt%) was also incorporated in the emulsions to determine the influence of triacylglycerol (TAG) crystallinity on BC bioaccessibility and stability during storage under accelerated lighting conditions. TAG crystallinity altered the colloidal fat crystal network properties and ultimately impacted lipid digestion, attenuating early static in vitro lipolysis for the PS emulsions compared to the PO emulsion. This correlated well with TIM-1 bioaccessibility trends and with results from our results of a previous human study wherein the rise in postprandial TAG was delayed when healthy men consumed PS-SE versus PS-LE. The presence of crystalline TAG modestly accelerated BC degradation, and did not improve preservation nor alter BC in vitro bioaccessibility.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) I-Cognitive Function and Metabolic Risk.

Neonatal nutritional supplements are widely used to improve growth and development but may increase risk of later metabolic disease, and effects may differ by sex. We assessed effects of supplements on later development and metabolism. We searched databases and clinical trials registers up to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter cognitive impairment in toddlers (13 trials, n = 1410; adjusted relative risk (aRR) 0.88 [95% CI 0.68, 1.13]; p = 0.31) or older ages, nor alter metabolic risk beyond 3 years (5 trials, n = 438; aRR 0.94 [0.76, 1.17]; p = 0.59). However, supplementation reduced motor impairment in toddlers (13 trials, n = 1406; aRR 0.76 [0.60, 0.97]; p = 0.03), and improved motor scores overall (13 trials, n = 1406; adjusted mean difference 1.57 [0.14, 2.99]; p = 0.03) and in girls not boys (p = 0.03 for interaction). Supplementation lowered triglyceride concentrations but did not affect other metabolic outcomes (high-density and low-density lipoproteins, cholesterol, fasting glucose, blood pressure, body mass index). Macronutrient supplementation for infants born small may not alter later cognitive function or metabolic risk, but may improve early motor function, especially for girls.

Sex-Specific Effects of Nutritional Supplements for Infants Born Early or Small: An Individual Participant Data Meta-Analysis (ESSENCE IPD-MA) II: Growth.

Neonatal nutritional supplements may improve early growth for infants born small, but effects on long-term growth are unclear and may differ by sex. We assessed the effects of early macronutrient supplements on later growth. We searched databases and clinical trials registers from inception to April 2019. Participant-level data from randomised trials were included if the intention was to increase macronutrient intake to improve growth or development of infants born preterm or small-for-gestational-age. Co-primary outcomes were cognitive impairment and metabolic risk. Supplementation did not alter BMI in childhood (kg/m2: adjusted mean difference (aMD) -0.11[95% CI -0.47, 0.25], p = 0.54; 3 trials, n = 333). Supplementation increased length (cm: aMD 0.37[0.01, 0.72], p = 0.04; 18 trials, n = 2008) and bone mineral content (g: aMD 10.22[0.52, 19.92], p = 0.04; 6 trials, n = 313) in infancy, but not at older ages. There were no differences between supplemented and unsupplemented groups for other outcomes. In subgroup analysis, supplementation increased the height z-score in male toddlers (aMD 0.20[0.02, 0.37], p = 0.03; 10 trials, n = 595) but not in females, and no significant sex interaction was observed (p = 0.21). Macronutrient supplementation for infants born small may not alter BMI in childhood. Supplementation increased growth in infancy, but these effects did not persist in later life. The effects did not differ between boys and girls.

Octylcyanoacrylate tissue adhesive versus suture wound repair in a contaminated wound model.

BACKGROUND: Octylcyanoacrylate tissue adhesive is a topical wound closure that precludes the need for foreign bodies (sutures) to close wounds. It also has an in vitro antimicrobial effect when standard disc sensitivity tests are used. METHODS: To determine whether contaminated wounds closed with octylcyanoacrylate tissue adhesive will have a lower infection rate compared with wounds closed with 5-0 monofilament sutures, we designed a randomized, blinded, experimental animal study. Two incisions were made on 20 albino guinea pigs. The wounds were contaminated with 10(5) Staphylococcus aureus ATCC 12600 and randomly assigned to be closed with either topical octylcyanoacrylate tissue adhesive or percutaneous 5-0 polypropylene suture. Five days later the adhesive and sutures were removed, and a section of the wound was given to a histopathologist blinded to the type of wound closure. The wound was determined to be infected if inflammatory cells with intracellular cocci were seen. The rest of the wound was opened and examined for clinical evidence of infection. Quantitative bacteriologic analysis was performed. RESULTS: Five wounds in the tissue adhesive group were sterile on day 5, whereas all sutured wounds had positive cultures (25% versus 0%, p < 0.05). Fewer wounds in the tissue adhesive group were determined to be infected by histologic and clinical criteria (0% versus 55%, p < 0.001, and 20% versus 65%, p < 0.01, respectively). Agreement on the determination of infection by histologic and clinical criteria yielded a kappa coefficient of 0.46 (95% confidence interval [GI], 0.19 to 0.73). An infection criterion of 10(5) colony-forming units/gm of tissue correlated poorly with clinical and histologic infection rates (0.19 [95% CI, -0.06 to 0.44] and 0.13 [95% CI, -0.05 to 0.31], respectively). CONCLUSIONS: Contaminated wounds closed with sutures had higher infection rates compared with those reported with topical tissue adhesive. The amount of colonization may not be an accurate method to determine infection.

Acute central and peripheral demyelination associated with Mycoplasma pneumoniae.

A 7-year-old female presented with Mycoplasma pneumoniae pneumonitis and a progressive ascending limb paralysis. She developed severe respiratory distress, requiring ventilation, and became apparently unresponsive with fixed dilated pupils. Peripheral nerves were inexcitable in nerve-conduction studies. Magnetic resonance imaging of the brain revealed evidence of extensive demyelination. Anti-GM1 immunoglobulin M antibody titers were raised. She improved after a second course of intravenous immunoglobulin and eventually made a full recovery.

BQ-153, a novel endothelin (ET)A antagonist, attenuates the renal vascular effects of endothelin-1.

Endothelin (ET)-1, leukotriene D4 and the thromboxane analogue, U-44069, were all shown to produce dose-dependent reductions in renal blood flow after direct injection into the renal artery of anaesthetized pigs. The effects of ET-1 differed from the other two mediators in that ET-1 caused a transient vasodilator followed by a prolonged vasoconstrictor response. The pressor response was not mediated by the secondary release of either leukotriene D4 or thromboxane A2 as evidenced by the lack of effect of appropriate receptor antagonist MK571 (3-[-2(7-chloro-2 quinolinyl) ethenyl]phenyl[3-(dimethylamino-3-oxopropyl)thio]methyl thio propionic acid) and L-670,596 respectively. This response, however, could be inhibited in a dose-dependent fashion by the selective ETA antagonist, BQ-153 (cyclo-D-sulphalanine-L-Pro-D-Val-L-Leu-D-Trp-). Following blockade by BQ-153 the vasodilator response was unaffected and a residual pressor response remained, suggesting that either or both of these effects were mediated either through an ETB or a novel, as yet undefined, endothelin receptor.

Efficacy and tolerability of levetiracetam in children aged 10 years and younger: a clinical experience.

Levetiracetam is a new anti-epileptic drug that is currently not licensed for use in children. Studies in adults suggest that it may be a useful adjunctive treatment both in partial onset and generalised epilepsy. A retrospective case notes review of 26 children age 10 years and under with refractory epilepsy was undertaken to evaluate the efficacy and safety of the drug. The drug appeared to be most effective in children with partial onset seizures and least effective in those with myoclonic seizures. Sixty-one percent of patients showed a good response to levetiracetam with at least a 50% reduction in seizure frequency with two of these 26 children with previously refractory epilepsy becoming seizure-free. Levetiracetam was also found to be well-tolerated with very few reported side-effects.

The serological diagnosis of bovine brucellosis: an evaluation of the complement fixation, serum agglutination and rose bengal tests.

In a collaborative investigation in which 4 laboratories took part, the Rose Bengal Test (RBT), Serum Agglutination Test (SAT) and 4 different Complement Fixation (CFT) techniques were evaluated in selected cattle for the diagnosis of bovine brucellosis, by comparing the results they gave with the bacteriological examination of a selection of lymph nodes taken from the same animals at slaughter. The RBT correctly classified all but 1 of 79 culture-positive cattle, but was more often positive in culture-negative animals than the other tests. The RBT may be most useful as a screen test. 11% of the culture-positive cattle had SAT titres below 100 iu and almost 4% of them had less than 30 iu. However, the SAT was more effective in cattle vaccinated with the 45/20 vaccine. The CFT, in 1 of 4 techniques used, identified all of the culture-positive cattle at a serum dilution of 1/4 or above and was considered to be far superior to the SAT as a diagnostic test, except perhaps in cattle vaccinated with the 45/20 vaccine.

Healthy staff, healthy profits.

This article discusses the development and contemporary scope for practice of occupational health nurses whose names appear on Part 1 of the Professional Register of the UK Central Council for Nursing Midwifery and Health Visiting (UKCC) and who hold a post-registration qualification in occupational health nursing recorded with the UKCC.

Uvulopalatopharyngoplasty versus laser-assisted uvulopalatopharyngoplasty in the treatment of snoring.

OBJECTIVE: This study was performed to compare the efficacy, pain, and complication rates between laser-assisted uvulopalatopharyngoplasty and conventional tonsillectomy and uvulopalatopharyngoplasty. METHOD: Eighty patients who had undergone the laser procedure and 29 the conventional procedure were studied prospectively. Snoring was measured using a new numeric snoring scale. RESULTS: There were no statistically significant differences between groups for final snoring scores, pain, or complication rates. The criteria for selecting uvulopalatopharyngoplasty candidates, which is described, resulted in a 97% success rate in the treatment of snoring. CONCLUSION: Laser-assisted uvulopalatopharyngoplasty and conventional tonsillectomy and uvulopalatopharyngoplasty are equally effective in the management of snoring in correctly selected patients. They are similarly painful procedures. A new and simple numeric snoring scale is described.

Ossicular chain reconstruction using a new tissue adhesive.

HYPOTHESIS: A new medical-grade cyanoacrylate tissue adhesive will improve the results of ossicular chain reconstruction in a rat model. BACKGROUND: An ideal tissue adhesive has long been awaited by otologists. Studies examining the older cyanoacrylates have demonstrated variable efficacy and toxicity. Octylcyanoacrylate is a new tissue adhesive that has many ideal properties for otologic surgery. METHODS: Thirteen female C-D rats were anesthetized, and preoperative auditory brainstem response (ABR) testing was performed. A left antrotomy was performed, and the incus was removed. In the adhesive group, the incus was dipped in octylcyanoacrylate and interposed between the tympanic membrane and the stapes; no adhesive was used in the control group. At 8 weeks, postoperative ABR was performed, the integrity of the ossicular chain inspected, and histopathologic analysis of the temporal bones performed. Statistical comparison of ABR results was performed with the Mann-Whitney test. RESULTS: Seven rats were randomized to the adhesive group and six to the control group, of which four survived. There were no histopathologic differences in the temporal bones of the animals other than the presence of mild foreign body reaction around the ossicular chain of the animals in the adhesive group. The ossicular chain was not intact in two of the four controls, whereas the rest were intact at 8 weeks. Postoperative air conduction ABR results (mean dB sound pressure level) (62.5 control versus 34.3 adhesive, p = 0.010) and air-bone gaps (47.5 control versus 18.9 adhesive, p = 0.008) were significantly better in the adhesive group. CONCLUSIONS: This new medical-grade tissue adhesive improves the hearing results of ossicular chain reconstruction, with no apparent histotoxicity in this animal model.

Tympanic membrane patching with bandage contact lens after removal of ventilation T tubes.

OBJECTIVE: Early closure of the tympanic membrane, after removal of longstanding ventilation T tubes (VTs), is a desirable outcome. A prospective randomized control study was undertaken to determine if spontaneous healing of the tympanic membrane is promoted with a bandage contact lens (BCL). METHOD: Thirty-nine paediatric patients, who required removal of VTs under general anaesthesia, were selected. After removal of the ventilation tubes, one tympanic membrane was randomly selected for patching with a BCL, while the other underwent conservative management. Follow-up examination was performed at 2 weeks. Remaining perforations of the tympanic membranes were noted. The mean length of time VTs were present was 35.7 months. RESULTS: Chi-square analysis reveals that a significantly greater proportion of tympanic membranes patched with a BCL were healed at 2 weeks (p < .005). CONCLUSIONS: Thus, promotion of spontaneous healing with BCL may allow for decreased risk of infection, improved hearing, and earlier avoidance of precautions necessary for perforated tympanic membranes. Also, it is possible that promoting spontaneous healing at the early phase may decrease the number of persistent tympanic membrane perforations after VT removal.

Octylcyanoacrylate: a new medical-grade adhesive for otologic surgery.

HYPOTHESIS: The adhesive octylcyanoacrylate is not associated with significant inner ear toxicity in a guinea pig model. BACKGROUND: Many cyanoacrylate adhesives have been investigated for use in otologic surgery, but variable ototoxicity has been reported. Octylcyanoacrylate is a medical-grade adhesive with many properties that make it ideal for use in the ear. It is free of contaminants; it forms a strong, flexible bond; and it inhibits the growth of gram-positive organisms in culture. This is the first study to assess the ototoxicity of this new adhesive. METHODS: Fourteen adult guinea pigs were used. Preoperative auditory brainstem responses (ABRs) were determined. Bilateral antrotomies were performed, and the ears were randomized to adhesive and control (saline) groups. In the adhesive ears. 0.5 or 0.1 mL of octylcyanoacrylate was instilled into the middle ear. Eight weeks later, postoperative ABRs were determined, the animals were killed, and the temporal bones were removed. Middle ear changes were noted, and the ossicular chain was assessed. Cochlear hair cell analyses were performed. Histologic assessment of the middle ear mucosa was performed. RESULTS: There was a higher incidence of conductive hearing loss in the adhesive group secondary to fixation of the ossicular chain, but there was no significant difference in bone conduction thresholds. The median postoperative bone conduction thresholds (dB peak sound pressure level) was 15.0 in the control group and 17.5 in the adhesive group, p = 0.89. There was also no significant difference in inner hair cell counts (0.4% vs. 0.5% median hair cell loss, p = 0.72) or outer hair cell counts (3.7% vs. 3.0% median hair cell loss, p = 0.23) for the adhesive and control groups, respectively. Histopathologic analysis of the middle ear mucosa demonstrated variable mild to moderate foreign body reaction with no evidence of mucosal ulceration or necrosis. CONCLUSIONS: A large amount of octylcyanoacrylate placed in the middle ear of the guinea pig did not cause any morphologic or functional evidence of inner ear toxicity. This new adhesive is a promising tool for otologic surgery.

A randomized trial comparing octylcyanoacrylate tissue adhesive and sutures in the management of lacerations.

OBJECTIVE: To assess the effectiveness of a new tissue adhesive for laceration closure. DESIGN: A prospective, randomized controlled trial. SETTING: An adult teaching hospital. PARTICIPANTS: One hundred thirty patients with 136 lacerations who consented to enrollment during a 5-month period. The lacerations included all eligible nonmucosal facial lacerations, as well as selected extremity and torso lacerations (not on hands, feet, or joints). One hundred six lacerations were available for early follow-up, and 98 were available for 3-month evaluation. INTERVENTIONS: Lacerations were randomly allocated to have skin closure with octylcyanoacrylate adhesive or monofilament suture. MAIN OUTCOME MEASURE: A 3-month photograph of the wound was assigned a cosmesis score on a previously validated 100-mm visual analog cosmesis scale by a plastic surgeon who was unaware of the method of wound closure. RESULTS: There were no differences in the mean visual analog cosmesis scores (67 mm for octylcyanoacrylate vs 68 mm for sutures; P=.65). Similarly, there was no difference in the percentage of early (80% vs 82%; P=.80) or late (72% vs 75%; P=.74) optimal wound evaluation scores. The tissue adhesive was a faster method of wound repair (3.6 vs 12.4 minutes; P<.001) as well as being less painful (visual analog pain scores, 7.2 vs 18.0 mm; P<.001). CONCLUSIONS: Octylcyanoacrylate tissue adhesive effectively closes selected lacerations. This relatively painless and fast method of wound repair can replace the need for suturing several million lacerations each year.

Tissue adhesive versus suture wound repair at 1 year: randomized clinical trial correlating early, 3-month, and 1-year cosmetic outcome.

STUDY OBJECTIVE: To compare the 1-year cosmetic outcome of wounds treated with octylcyanoacrylate tissue adhesive and monofilament sutures and to correlate the early, 3-month, and 1-year cosmetic outcomes. METHODS: We prospectively randomized 136 cases of traumatic laceration to repair with octylcyanoacrylate tissue adhesive or 5-0 or smaller monofilament suture. A wound score was assigned by a research nurse, and validated by a second nurse blinded to the treatment, at 5 to 10 days after injury (early), 3 months, and 1 year. Standardized photographs were taken at 3 months and 1 year and shown to a cosmetic surgeon blinded to the method of closure, who rated the wounds on a validated cosmesis scale. RESULTS: We were able to examine 77 lacerations at 1 year for follow-up. No differences were found in the demographic or clinical characteristics between groups. Likewise, at 1 year no difference was found in the optimal wound scores (73% versus 68%, P =.60) or in visual analog scale cosmesis scores (69 versus 69 mm, P =.95) for octylcyanoacrylate and sutures, respectively. Agreement was poor between early and 3-month wound scores (kappa=.34; 95% confidence interval [CI],.10 to.58) but a strong association existed between 3-month and 1-year wound scores (kappa=.71; 95% CI,.52 to.90). We noted a moderate correlation between 3-month and 1-year results on the visual analog cosmesis scale (intraclass correlation,.48; 95% CI, .30 to.63). CONCLUSION: One year after wound repair, no difference is noted in the cosmetic outcomes of traumatic lacerations treated with octylcyanoacrylate tissue adhesive and sutures. The assessment of wounds 3 months after injury and wound repair provides a good measure of long-term cosmetic outcome.