The effects of different sampling techniques on peripheral post mortem tryptase levels: a recommended sampling method.

Different sampling techniques can impact on post mortem tryptase levels. A previous study demonstrated significantly lower femoral post mortem total tryptase levels in samples collected via transcutaneous aspiration compared with directly sampling during internal examination. However, an outlier with high tryptase level was noted in one transcutaneous aspiration sample. This 6-month prospective study compared total post mortem tryptase levels between 21 paired aspirated venous and arterial femoral blood samples, and 19 paired aspirated and cutdown femoral venous blood samples in non-anaphylactic deaths only. No statistical differences were demonstrated between the different sampling methods. However, four outlier cases with higher tryptase levels in aspirated arterial and femoral cutdown samples compared with aspirated venous femoral samples were noted. The reasons for the outliers may be due to the bloods collected from these two methods being contaminated by central arterial and venous blood with high tryptase levels respectively. None of the aspirated venous femoral post mortem tryptase levels were above recognized post mortem tryptase cutoff to diagnose anaphylaxis. This study recommends aspirating blood samples from a clamped femoral/external iliac vein for post mortem tryptase analysis should be defined as the gold standard. Further study using the recommended sampling method on post mortem tryptase levels in non-anaphylactic and anaphylactic cases is warranted.

Differences in sampling techniques on total post-mortem tryptase.

BACKGROUND: The measurement of mast cell tryptase is commonly used to support the diagnosis of anaphylaxis. In the post-mortem setting, the literature recommends sampling from peripheral blood sources (femoral blood) but does not specify the exact sampling technique. Sampling techniques vary between pathologists, and it is unclear whether different sampling techniques have any impact on post-mortem tryptase levels. AIM: The aim of this study is to compare the difference in femoral total post-mortem tryptase levels between two sampling techniques. METHODS: A 6-month retrospective study comparing femoral total post-mortem tryptase levels between (1) aspirating femoral vessels with a needle and syringe prior to evisceration and (2) femoral vein cut down during evisceration. RESULTS: Twenty cases were identified, with three cases excluded from analysis. There was a statistically significant difference (paired t test, p < 0.05) between mean post-mortem tryptase by aspiration (10.87 ug/L) and by cut down (14.15 ug/L). The mean difference between the two methods was 3.28 ug/L (median, 1.4 ug/L; min, - 6.1 ug/L; max, 16.5 ug/L; 95% CI, 0.001-6.564 ug/L). CONCLUSIONS: Femoral total post-mortem tryptase is significantly different, albeit by a small amount, between the two sampling methods. The clinical significance of this finding and what factors may contribute to it are unclear. When requesting post-mortem tryptase, the pathologist should consider documenting the exact blood collection site and method used for collection. In addition, blood samples acquired by different techniques should not be mixed together and should be analyzed separately if possible.

Do delays in radiology lead to breaches in the 4-hour rule?

AIM: To assess trends in medical imaging requests before and after the 4-hour rule commenced and to assess the imaging time component of emergency department (ED) length of stay (LOS). MATERIALS AND METHODS: Retrospective analysis of ED patients and imaging requests 1 year prior to and 3 years after implementation of the 4-hour rule (April to December for 2011-2014) was performed at a single adult tertiary referral Level 1 trauma hospital with Level 6 ED. Logistic regression was used to evaluate trends in the number of ED patient presentations, patient triage categories, and imaging requests for these patients. The imaging component of the total ED LOS was compared for patients who met the 4-hour target and patients who did not. RESULTS: Compared to 2011 (before the 4-hour rule), ED presentations increased 4.74% in 2012, 12.7% in 2013, 21.28% in 2014 (p<0.01). Total imaging requests increased 23.05% in 2012, 48.04% in 2013, 60.77% in 2014 (p<0.01). For patients breaching the 4-hour rule, the mean time before radiology request was 2.4-2.8 hours; mean time from imaging request to completion was 1.2-1.3 hours; mean time from imaging completion to discharge from ED was the longest component of ED LOS (4.9-5.9 hours). CONCLUSIONS: There has been a significant increase in imaging requests, with a trend towards more CT and less radiography requests. Imaging requests for patients who breached the 4-hour target were made on average 2.4-2.8 hours after triage and average time after imaging in itself, exceeded 4 hours. Imaging is not likely a causative factor for patients breaching the 4-hour target.

Selective regulation of integrin--cytoskeleton interactions by the tyrosine kinase Src.

Cell motility on extracellular-matrix (ECM) substrates depends on the regulated generation of force against the substrate through adhesion receptors known as integrins. Here we show that integrin-mediated traction forces can be selectively modulated by the tyrosine kinase Src. In Src-deficient fibroblasts, cell spreading on the ECM component vitronectin is inhibited, while the strengthening of linkages between integrin vitronectin receptors and the force-generating cytoskeleton in response to substrate rigidity is dramatically increased. In contrast, Src deficiency has no detectable effects on fibronectin-receptor function. Finally, truncated Src (lacking the kinase domain) co-localizes to focal-adhesion sites with alpha v but not with beta 1 integrins. These data are consistent with a selective, functional interaction between Src and the vitronectin receptor that acts at the integrin-cytoskeleton interface to regulate cell spreading and migration.

Diffuse large B-cell lymphoma masquerading as orbital cellulitis.

Proptosis is commonly encountered in clinical practice. We report on a patient with acute proptosis, eyelid swelling, and chemosis, which was initially treated as cellulitis. After radiological and pathological assessments, a diagnosis of large B-cell lymphoma was made. The patient died within 2 months of presentation. Not all patients with proptosis have cellulitis. Proptosis, especially unilateral proptosis, should always lead to a radiological scan in case of malignancy.

Modulation of caseinate-stabilized model oil-in-water emulsions with soy lecithin.

Demands for plant-based food and beverage products have escalated in recent years. However, many commercial coffee creamers are still being made using dairy derivatives such as sodium caseinate. Therefore, there is a need to investigate the replacement of dairy based proteins with plant-based alternatives. This study was carried out to systematically investigate the properties of model O/W emulsions stabilized by either sodium caseinate (0.25 to 1.5%) or soy lecithin (0.5 to 1.5%). The model emulsions were made of 10% medium chain triglyceride (MCT) oil-in-water emulsions at pH 7. All model O/W emulsions exhibited whitish appearances similar to that of commercial creamers and were effective at lightening black coffee, except those containing the lowest emulsifier concentrations i.e., 0.25% caseinate or 0.5% lecithin. The lightness of the model emulsions depended on the type and level of emulsifier used, with soy lecithin-stabilized emulsions having similar lightening power compare to that stabilized by sodium caseinate. No feathering or free oil were observed in the whitened coffees at the highest emulsifier level used. Mixtures of caseinate and lecithin emulsifiers were also used and model O/W emulsions with similar physical properties to that stabilized by sodium caseinate alone were produced. The mixed emulsifier-stabilized model emulsions had similar lightness when added to coffee than those stabilized by the individual emulsifiers, suggesting similar stabilization mechanisms using these emulsifiers alone or in combination.

Conformal radiotherapy for hepatocellular carcinoma.

Technical advancements in radiation therapy (RT) have facilitated the safe delivery of conformal, dose-escalated radiation to a wide spectrum of hepatocellular carcinoma (HCC) patients. A variety of doses and RT fractionation schemes have been used, and RT has been used in combination with transarterial chemoembolization (TACE). Compared to untreated historical controls or those treated with TACE alone, outcomes following RT alone or TACE and RT are better. Despite advances in RT delivery, liver toxicity following RT remains a dose-limiting factor, and investigations to better understand the pathophysiology of RT-induced liver toxicity are warranted. For most tumors, RT can provide sustained local control. However, HCC tends to recur within the liver away from the irradiated volume, providing rationale for combining RT with systemic or regional therapies. There is a particular interest in combining RT with anti-VEGF-targeted agents for their independent activity in HCC as well as their radiation sensitization properties. Randomized trials of RT are warranted.

Post mortem vitreous magnesium in adult population.

BACKGROUND: The study of post mortem vitreous magnesium (Mg) is less common than sodium (Na), chloride (Cl) and potassium (K) in the forensic literature. There is no accepted normal range for post mortem vitreous Mg and the relationship between post mortem vitreous Mg levels and post mortem interval (PMI), other electrolyte levels, disease conditions, age and sex have not been fully established. AIM: To investigate the relationship of post mortem vitreous Mg with age, sex, PMI, vitreous electrolyte levels and diabetic status. METHODS: A retrospective study of 20 consecutive cases of diabetics and 20 non-diabetic adult deaths was performed. Spearman correlation and the permutation test were used to explore the relationship between post mortem vitreous Mg and continuous and categorical variables respectively. RESULTS: The mean post mortem vitreous Mg was 1.03mmol/L (95%CI: 0.98-1.08mmol/L). The absolute Spearman correlation coefficients (rho) between post mortem vitreous Mg with PMI, age, and other vitreous electrolytes (Na, Cl, and K) ranged between 0.04-0.21 (p>0.19). Post mortem vitreous Mg was statistically higher in diabetics (mean difference: 0.08mmol/L; area-under-the-curve=0.65 on receiver-operator-characteristic curve). No statistical difference was demonstrated between sexes (p=0.92). CONCLUSIONS: In our adult population, post mortem vitreous Mg did not correlate with age, PMI, other vitreous electrolytes (sodium, chloride and potassium) or sex. It was higher in diabetics, however had limited utility as a surrogate marker. Overall, post mortem Mg is steady in the early post mortem period with a mean of 1.03mmol/L.

Post mortem tryptase cut-off level for anaphylactic death.

Serum mast cell tryptase is used to support the diagnosis of anaphylaxis. The recommended clinical cut-off for total tryptase (<11.4µg/L) appears unsuitable in the post mortem setting due to largely unknown processes which result in significantly elevated levels in these samples. Consequently there is no widely accepted tryptase cut-off level for diagnosing an anaphylactic death. This 5-year retrospective study compared total tryptase levels in post mortem femoral blood in anaphylactic deaths and control. Univariate and multivariate analysis was used to assess the relative contribution of other factors (age, gender, post mortem interval, and presence of resuscitation) on post mortem tryptase levels. Nine anaphylactic deaths and 45 controls were identified. Receiver-operating characteristic (ROC) curve analysis identified an optimal cut-off of 53.8µg/L, with sensitivity of 89%, and specificity of 93%, for total post mortem tryptase in femoral blood to diagnosis anaphylaxis. No other factors showed any statistical significant contribution to post mortem tryptase elevation. Femoral total post mortem tryptase level of 53.8µg/L and above is a useful ancillary test in diagnosing an anaphylactic death.

Elevation of post mortem vitreous humour sodium and chloride levels can be used as a reliable test in cases of suspected salt water drowning when the immersion times are less than one hour.

BACKGROUND: Previous studies in salt water drowning deaths (SWD) demonstrated an observable elevation of post mortem vitreous sodium and chloride (PMVSC) levels. It remains unclear what the underlying mechanism responsible for this change is: whether this is due to rapid electrolyte changes from salt water inhalation/ingestion during drowning or from electrolyte diffusion and/or osmosis across the outer coats of the eyeballs during immersion. A recent animal study using sacrificed bovine eyeballs immersed in salt water demonstrated no significant elevations in PMVSC when immersed for less than one hour. Assuming similar physical properties between human and bovine, we extrapolate that an elevation in PMVSC in SWD with immersion times of less than one hour (SWD-1) would not be from immersion, but from drowning. AIM: Investigate whether there is an elevation in PMVSC in SWD-1. METHODS: Retrospective study comparing PMVSC in SWD-1 with controls from 2012 to 2015 inclusive. RESULTS: PMVSC in SWD-1 was significantly elevated compared with controls. A PMVSC of 259mmol/L has a sensitivity, specificity and likelihood ratio of 0.9, 0.9 and 7.6, respectively. CONCLUSION: The elevation in PMVSC in SWD-1 is due to drowning. A PMVSC of 259mmol/L and above is a reliable ancillary test in diagnosing drowning in bodies immersed in salt water for less than one hour.

Implementing Intensity-modulated Radiotherapy with Simultaneous Integrated Boost for Anal Cancer: 3 Year Outcomes at Two Sydney Institutions.

AIMS: Modern chemoradiotherapy used for the treatment of anal cancer has significant acute toxicity. Intensity-modulated radiotherapy (IMRT) may reduce these side-effects. We report our experience implementing IMRT with simultaneous boost at the Sydney Cancer Centre and Royal North Shore Hospital. MATERIALS AND METHODS: We retrospectively collected acute toxicity data on all consecutive patients treated definitively with IMRT between January 2008 and December 2011. Patients received concurrent 5-fluorouracil and mitomycin-C. The radiotherapy dose varied by stage in accordance with the Radiation Therapy Oncology Group (RTOG) 0529 protocol. The first 30 plans were evaluated for adherence to RTOG 0529 dose specifications. Locoregional control and survival outcomes were analysed in July 2014. RESULTS: We included 42 patients (stage I 12%; II 41%; III 45%) with a median follow-up time of 43 months. At 3 years the locoregional control was 94% (95% confidence interval: 78-99), overall survival was 92% (95% confidence interval: 78-97), disease-free survival was 89% (95% confidence interval: 73-96), metastasis-free survival was 89% (95% confidence interval: 73-96) and colostomy-free survival was 89% (95% confidence interval: 72-96). There was no acute grade 4 toxicity. Acute grade 3 toxicity rates were: dermatological (33%), gastrointestinal (14%) and haematological (19%). Twenty-six per cent of patients were hospitalised for treatment-related toxicity. Only 12% required a treatment break greater than 3 days. All patients achieved RTOG 0529 planning target volume dose specifications. Most critical organ dose constraints were either met or met with minor deviation. The exception was 76% major deviation in small bowel constraints. Despite this no increase in gastrointestinal toxicity was observed. CONCLUSIONS: IMRT with simultaneous integrated boost is safe and well tolerated in an unselected population. Most dose specifications are achievable. Excellent locoregional control and survival outcomes are achievable outside of a clinical trial setting.

The diagnostic value of CT myelography, MR myelography, and both in neonatal brachial plexus palsy.

BACKGROUND AND PURPOSE: Although most infants with brachial plexus palsy recover function spontaneously, approximately 10-30% benefit from surgical treatment. Pre-operative screening for nerve root avulsions is helpful in planning reconstruction. Our aim was to compare the diagnostic value of CT myelography, MR myelography, and both against a surgical criterion standard for detection of complete nerve root avulsions in birth brachial plexus palsy. MATERIALS AND METHODS: Nineteen patients who underwent a preoperative CT and/or MR myelography and subsequent brachial plexus exploration were included. Imaging studies were analyzed for the presence of abnormalities potentially predictive of nerve root avulsion. Findings of nerve root avulsion on surgical exploration were used as the criterion standard to assess the predictive value of imaging findings. RESULTS: Ninety-five root levels were examined. When the presence of any pseudomeningocele was used as a predictor, the sensitivity was 0.73 for CT and 0.68 for MR imaging and the specificity was 0.96 for CT and 0.97 for MR imaging. When presence of pseudomeningocele with absent rootlets was used as the predictor, the sensitivity was 0.68 for CT and 0.68 for MR imaging and the specificity was 0.96 for CT and 0.97 for MR imaging. The use of both CT and MR imaging did not increase diagnostic accuracy. Rootlet findings in the absence of pseudomeningocele were not helpful in predicting complete nerve root avulsion. CONCLUSIONS: Findings of CT and MR myelography were highly correlated. Given the advantages of MR myelography, it is now the single technique for preoperative evaluation of nerve root avulsion at our institution.

Retrospective case series on the long-term visual and intraocular pressure outcomes of phacomorphic glaucoma.

PURPOSE: To analyse the long-term visual acuity (VA) and intraocular pressure (IOP) outcomes in phacomorphic glaucoma. PATIENTS AND METHODS: A retrospective analysis of 100 consecutive, acute phacomorphic glaucoma cases from January 2000 to April 2009 was conducted at The Caritas Medical Centre in Hong Kong. All cases underwent cataract extraction after IOP control with medication and/or laser. RESULTS: During a 3.1±2.6-year follow-up, the mean visual improvement was 1.1±0.9 LogMAR units with improvements in 81.7% of cases. A shorter duration from symptoms to cataract extraction resulted in greater visual improvement (r(2)=0.1, P=0.001). In all, 80.5% of the cases had IOP≤21 mm Hg without any glaucoma treatment; 19.5% required 1.6±0.7 glaucoma eye drops; and 3.7% required additional laser iridotomy or trabeculectomy for IOP control at 1.8±2.3 years. The vertical cup-disc ratio (VCDR) of the index eye was 0.6±0.3. Gonioscopy revealed an averaged Shaffer grading of 3.0±1.0 and 99±90 degrees of peripheral anterior synechiae (PAS). The Humphrey automated perimetry mean deviation was 5.2±2.7 and the pattern standard deviation was -15.9±10. CONCLUSION: Over 80% of phacomorphic patients had long-term visual improvements and normalization of IOP after cataract extraction. A shorter attack seemed to offer better VA. Post-operatively, most have open angles with some degree of PAS formation, and glaucomatous optic neuropathy is evident from enlarged VCDRs and visual field defects. At least 2 years of follow-up is useful to detect a 20% glaucoma progression possibly requiring additional glaucoma treatments.

Radioresistant malignant myoepithelioma of the breast with high level of ataxia telangiectasia mutated protein.

Malignant myoepithelioma of the breast (MMB) is a rare and often aggressive disease with poor prognosis. Little is known regarding its optimal treatment and progression. We describe the clinical history of a woman following excision of a benign adenomyoepithelioma which recurred years later as a radioresistant malignant myoepithelioma with high levels of ataxia telangiectasia mutated protein and mutant p53 (Cys135Phe). MMB requires close follow-up and aggressive treatment. If adjuvant radiotherapy is adopted to improve local control, minimal postoperative delay and higher doses than for standard post-mastectomy radiation are recommended.

Oculogyric crisis after metoclopramide therapy.

Oculogyric crisis developed in a 21-year-old girl after 5 oral doses of 10 mg of metoclopramide. The symptoms were relieved by i.v. administration of diphenhydramine hydrochloride. Although ocular side effects of metoclopramide are rare, it can induce an alarming oculogyric crisis in some sensitive subjects. The mechanism of oculogyric crises is unclear but the characteristics of the condition and some known causes are discussed. Advice is given on optometric management.