CT diagnosis of ilioinguinal lymph node metastases in melanoma using radiological characteristics beyond size and asymmetry.

BACKGROUND: Diagnosis of lymph node (LN) metastasis in melanoma with non-invasive methods is challenging. The aim of this study was to evaluate the diagnostic accuracy of six LN characteristics on CT in detecting melanoma-positive ilioinguinal LN metastases, and to determine whether inguinal LN characteristics can predict pelvic LN involvement. METHODS: This was a single-centre retrospective study of patients with melanoma LN metastases at a tertiary cancer centre between 2008 and 2016. Patients who had preoperative contrast-enhanced CT assessment and ilioinguinal LN dissection were included. CT scans containing significant artefacts obscuring the pelvis were excluded. CT scans were reanalysed for six LN characteristics (extracapsular spread (ECS), minimum axis (MA), absence of fatty hilum (FH), asymmetrical cortical nodule (CAN), abnormal contrast enhancement (ACE) and rounded morphology (RM)) and compared with postoperative histopathological findings. RESULTS: A total of 90 patients were included. Median age was 58 (range 23-85) years. Eighty-eight patients (98 per cent) had pathology-positive inguinal disease and, of these, 45 (51 per cent) had concurrent pelvic disease. The most common CT characteristics found in pathology-positive inguinal LNs were MA greater than 10 mm (97 per cent), ACE (80 per cent), ECS (38 per cent) and absence of RM (38 per cent). In multivariable analysis, inguinal LN characteristics on CT indicative of pelvic disease were RM (odds ratio (OR) 3.3, 95 per cent c.i. 1.2 to 8.7) and ECS (OR 4.2, 1.6 to 11.3). Cloquet's node is known to be a poor predictor of pelvic spread. Pelvic LN disease was present in 50 per cent patients, but only 7 per cent had a pathology-positive Cloquet's node. CONCLUSION: Additional CT radiological characteristics, especially ECS and RM, may improve diagnostic accuracy and aid clinical decisions regarding the need for inguinal or ilioinguinal dissection.

Amylase quantification in the terminal Ileum following formation of an Ileostomy.

Amylase is elevated in the foregut and has been used to confirm anastomotic integrity after pancreatic surgery. The physiological activity of pancreatic enzymes in the ileum has been studied in healthy volunteers but not quantitated with the simple and readily available amylase measurements employed with serum tests. We aim to quantitate the levels of amylase in the terminal ileum. This was a prospective, non-randomised, non-blinded, consecutive cohort study conducted at the Royal Brisbane and Women's Hospital. Consecutive patients undergoing routine surgery with an ileostomy were invited to participate in the study. Ileostomy effluent was collected and analysed daily for the first 5 post-operative days. This validation cohort included 8 males and 3 females, with a mean age of 49 years. Median daily amylase levels ranged from 4470 U/L to 23,000 U/L, with no specimens falling within the laboratory serum reference range of 40 to 130 U/L. Two specimens were not available on day one post-operative due to complete ileus. The sample size of 11 patients is small but was considered sufficient given that 55 effluent specimens were anticipated for analysis. Amylase levels remain highly elevated as the enzyme transits through the length of the small intestine and measured in the terminal ileum, and can be readily quantitated by the existing testing methodology routinely available.

Drain fluid amylase as a sensitive biomarker for the early detection of anastomotic leakage in ileal pouch surgery.

AIM: We studied the levels of amylase in drain fluid to investigate its utility as a biomarker of anastomotic leak in ileal pouch patients who did not have a covering loop ileostomy. The luminal contents of the small intestine are high in amylase. Ileal J pouches are formed for restoration of continuity in patients with ulcerative colitis after removal of the colon and rectum. A drain is placed alongside the ileal pouch in the pelvis. METHOD: This study is a retrospective analysis of prospectively collected daily drain fluid amylase levels in consecutive patients undergoing restorative proctectomy and ileal J pouch anal anastomosis, without a covering loop ileostomy, between November 2016 and April 2018. RESULTS: Thirteen patients underwent surgery without a covering loop ileostomy. Two patients suffered an anastomotic leak and were returned to theatre, one on day 5 and the other on day 6 postoperatively. The mean daily drain fluid amylase level in those who did not leak was between 25 and 46 U/l with a range of 22-139 U/l for all samples collected. In the two patients who suffered a clinical leak the drain fluid amylase level rose to 22 432 and 10 212 U/l on the day of clinical leak diagnosis. The mean rectal tube (intraluminal) amylase level was 63 097 U/l as measured on day 1 postoperatively. CONCLUSION: In this small cohort of patients, the measurement of drain fluid amylase is a highly sensitive biomarker of clinical anastomotic leak.

Urinary incontinence in male dogs under primary veterinary care in England: prevalence and risk factors.

OBJECTIVE: To estimate prevalence and identify demographic risk factors for urinary incontinence in male dogs. METHODS AND METHODS: The study population included all dogs within the VetCompass database from September 1, 2009 to July 7, 2013. Electronic patient records were searched for urinary incontinence cases; demographic and clinical information were extracted and analysed. RESULTS: Of 109,428 male dogs attending 119 clinics in England, there were an estimated 1027 dogs diagnosed with urinary incontinence, giving a prevalence of 0.94% (95% confidence interval: 0.88 to 1.00). Breeds with highest odds of incontinence in male dogs (compared with mixed breed dogs) included the bull mastiff (odds ratio: 17.21, 95% confidence interval: 6.65 to 44.56, case=5, non-case=314, P<0.001), Irish red setter (odds ratio: 12.79, 95% confidence interval: 4.83 to 33.84, case=5, non-case=142, P<0.001), fox terrier (odds ratio: 9.60, 95% confidence interval: 3.68 to 25.05, case=5, non-case=176, P < 0.001), bulldog (odds ratio: 5.72, 95% confidence interval: 2.24 to 14.59, case=5, non-case=929, P<0.001) and boxer (odds ratio: 3.65, 95% confidence interval: 1.84 to 7.25, case=10, non-case=1470, P<0.001). Increased odds of urinary incontinence were associated with greater age (age 9 to 12 years, odds ratio: 10.46, 95% confidence interval: 6.59 to 16.62, n=12,348, P<0.001) and being insured (odds ratio: 1.96, 95% confidence interval: 1.53 to 2.51, n=26,202, P<0.001). There was no association with castration or bodyweight using multi-variable analysis. CLINICAL SIGNIFICANCE: The overall prevalence of urinary incontinence in male dogs is approximately 1%, which may be higher than expected given the sparsity of reports describing this problem. In contrast to bitches, neutering and bodyweight were not associated with greater odds of urinary incontinence, which is important when giving neutering advice.

Treatment of bleeding episodes in haemophilia A complicated by a factor VIII inhibitor in patients receiving Emicizumab. Interim guidance from UKHCDO Inhibitor Working Party and Executive Committee.

Emicizumab is a bispecific antibody that activates FX to FXa in the absence of FVIII. It has been shown to reduce bleeding episodes in people with haemophilia A complicated by a FVIII inhibitor. Despite the protection against bleeds, some breakthrough bleeds are inevitable and these may require additional haemostatic treatment. Emicizumab has been associated with severe adverse events when co-administered with activated prothrombin complex concentrate. To minimize the risk of adverse events, the UK Haemophilia Centre Doctors' Organisation issues the following updated interim guidance to its Inhibitor Guidelines for managing patients receiving Emicizumab based on the limit published information available in February 2018.

International collaborative study for the calibration of proposed International Standards for thromboplastin, rabbit, plain, and for thromboplastin, recombinant, human, plain.

Essentials Two candidate International Standards for thromboplastin (coded RBT/16 and rTF/16) are proposed. International Sensitivity Index (ISI) of proposed standards was assessed in a 20-centre study. The mean ISI for RBT/16 was 1.21 with a between-centre coefficient of variation of 4.6%. The mean ISI for rTF/16 was 1.11 with a between-centre coefficient of variation of 5.7%. SUMMARY: Background The availability of International Standards for thromboplastin is essential for the calibration of routine reagents and hence the calculation of the International Normalized Ratio (INR). Stocks of the current Fourth International Standards are running low. Candidate replacement materials have been prepared. This article describes the calibration of the proposed Fifth International Standards for thromboplastin, rabbit, plain (coded RBT/16) and for thromboplastin, recombinant, human, plain (coded rTF/16). Methods An international collaborative study was carried out for the assignment of International Sensitivity Indexes (ISIs) to the candidate materials, according to the World Health Organization (WHO) guidelines for thromboplastins and plasma used to control oral anticoagulant therapy with vitamin K antagonists. Results Results were obtained from 20 laboratories. In several cases, deviations from the ISI calibration model were observed, but the average INR deviation attributabled to the model was not greater than 10%. Only valid ISI assessments were used to calculate the mean ISI for each candidate. The mean ISI for RBT/16 was 1.21 (between-laboratory coefficient of variation [CV]: 4.6%), and the mean ISI for rTF/16 was 1.11 (between-laboratory CV: 5.7%). Conclusions The between-laboratory variation of the ISI for candidate material RBT/16 was similar to that of the Fourth International Standard (RBT/05), and the between-laboratory variation of the ISI for candidate material rTF/16 was slightly higher than that of the Fourth International Standard (rTF/09). The candidate materials have been accepted by WHO as the Fifth International Standards for thromboplastin, rabbit plain, and thromboplastin, recombinant, human, plain.

Urinary incontinence in bitches under primary veterinary care in England: prevalence and risk factors.

OBJECTIVES: To estimate prevalence and demographic risk factors for urinary incontinence in bitches under primary veterinary care in England. METHODS: The study population included all bitches within the VetCompass database from September 1, 2009 to July 7, 2013. Electronic patient records were searched for urinary incontinence cases and additional demographic and clinical information was extracted. RESULTS: Of 100,397 bitches attending 119 clinics in England, an estimated 3108 were diagnosed with urinary incontinence. The prevalence of urinary incontinence was 3·14% (95% confidence intervals: 2·97 to 3·33). Medical therapy was prescribed to 45·6% cases. Predisposed breeds included the Irish setter (odds ratio: 8·09; 95% confidence intervals: 3·15 to 20·80; P< 0·001) and Dobermann (odds ratio: 7·98; 95% confidence intervals: 4·38 to 14·54; P< 0·001). Increased odds of a diagnosis of urinary incontinence were associated with: (1) weight at or above the mean adult bodyweight for the breed (odds ratio: 1·31; 95% confidence intervals: 1·12 to 1·54; P< 0·001), (2) age 9 to 12 years (odds ratio: 3·86; 95% confidence intervals: 2·86 to 5·20, P< 0·001), (3) neuter status (odds ratio: 2·23; 95% confidence intervals: 1·52 to 3·25, P< 0·001) and (4) being insured (odds ratio: 1·59; 95% confidence intervals: 1·34 to 1·88, P< 0·001). CLINICAL IMPACT: Clinical Impact: Urinary incontinence affects just over 3% of bitches overall but affects more than 15% of bitches in high-risk breeds including the Irish setter, Dobermann, bearded collie, rough collie and Dalmatian. These results provide an evidence base for clinicians to enhance clinical recommendations on neutering and weight control, especially in high-risk breeds.

Stereotactic radiosurgery planning of vestibular schwannomas: Is MRI at 3 Tesla geometrically accurate?

PURPOSE: MRI is a mandatory requirement to accurately plan Stereotactic Radiosurgery (SRS) for Vestibular Schwannomas. However, MRI may be distorted due not only to inhomogeneity of the static magnetic field and gradients but also due to susceptibility-induced effects, which are more prominent at higher magnetic fields. We assess geometrical distortions around air spaces and consider MRI protocol requirements for SRS planning at 3 T. METHODS: Hardware-related distortion and the effect of incorrect shimming were investigated with structured test objects. The magnetic field was mapped over the head on five volunteers to assess susceptibility-related distortion in the naso-oro-pharyngeal cavities (NOPC) and around the internal ear canal (IAC). RESULTS: Hardware-related geometric displacements were found to be less than 0.45 mm within the head volume, after distortion correction. Shimming errors can lead to displacements of up to 4 mm, but errors of this magnitude are unlikely to arise in practice. Susceptibility-related field inhomogeneity was under 3.4 ppm, 2.8 ppm, and 2.7 ppm for the head, NOPC region and IAC region, respectively. For the SRS planning protocol (890 Hz/pixel, approximately 1 mm3 isotropic), susceptibility-related displacements were less than 0.5 mm (head), and 0.4 mm (IAC and NOPC). Large displacements are possible in MRI examinations undertaken with lower receiver bandwidth values, commonly used in clinical MRI. Higher receiver bandwidth makes the protocol less vulnerable to sub-optimal shimming. The shimming volume and the CT-MR co-registration must be considered jointly. CONCLUSION: Geometric displacements can be kept under 1 mm in the vicinity of air spaces within the head at 3 T with appropriate setting of the receiver bandwidth, correct shimming and employing distortion correction.

Diagnostic laboratory for bleeding disorders ensures efficient management of haemorrhagic disorders.

Haemorrhagic disorders like Postpartum haemorrhage and Dengue haemorrhagic fever are life threatening and requires an active and efficient transfusion service that could provide the most appropriate blood product which could be effective in managing them. This would essentially require prompt identification of the coagulopathy so that the best available product can be given to the bleeding patient to correct the identified haemostatic defect which will help control the bleeding. This would only be possible if the transfusion service has a laboratory to correctly detect the haemostatic defect and that too with an accuracy and precision which is ensured by a good laboratory quality assurance practices. These same processes are necessary for the transfusion services to ensure the quality of the blood products manufactured by them and that it contains adequate amounts of haemostasis factors which will be good to be effective in the management of haemorrhagic disorders. These issues are discussed in detail individually in the management of postpartum haemorrhage and Dengue haemorrhagic fever including when these can help in the use of rFVIIa in Dengue haemorrhagic fever. The requirements to ensure good-quality blood products are made available for the management of these disorders and the same have also been described.

Alterations in coagulation following major liver resection.

The international normalised ratio is frequently raised in patients who have undergone major liver resection, and is assumed to represent a potential bleeding risk. However, these patients have an increased risk of venous thromboembolic events, despite conventional coagulation tests indicating hypocoagulability. This prospective, observational study of patients undergoing major hepatic resection analysed the serial changes in coagulation in the early postoperative period. Thrombin generation parameters and viscoelastic tests of coagulation (thromboelastometry) remained within normal ranges throughout the study period. Levels of the procoagulant factors II, V, VII and X initially fell, but V and X returned to or exceeded normal range by postoperative day five. Levels of factor VIII and Von Willebrand factor were significantly elevated from postoperative day one (p < 0.01). Levels of the anticoagulants, protein C and antithrombin remained significantly depressed on postoperative day five (p = 0.01). Overall, the imbalance between pro- and anticoagulant factors suggested a prothrombotic environment in the early postoperative period.

A Bayesian analysis of plutonium exposures in Sellafield workers.

The joint Russian (Mayak Production Association) and British (Sellafield) plutonium worker epidemiological analysis, undertaken as part of the European Union Framework Programme 7 (FP7) SOLO project, aims to investigate potential associations between cancer incidence and occupational exposures to plutonium using estimates of organ/tissue doses. The dose reconstruction protocol derived for the study makes best use of the most recent biokinetic models derived by the International Commission on Radiological Protection (ICRP) including a recent update to the human respiratory tract model (HRTM). This protocol was used to derive the final point estimates of absorbed doses for the study. Although uncertainties on the dose estimates were not included in the final epidemiological analysis, a separate Bayesian analysis has been performed for each of the 11 808 Sellafield plutonium workers included in the study in order to assess: A. The reliability of the point estimates provided to the epidemiologists and B. The magnitude of the uncertainty on dose estimates. This analysis, which accounts for uncertainties in biokinetic model parameters, intakes and measurement uncertainties, is described in the present paper. The results show that there is excellent agreement between the point estimates of dose and posterior mean values of dose. However, it is also evident that there are significant uncertainties associated with these dose estimates: the geometric range of the 97.5%:2.5% posterior values are a factor of 100 for lung dose, 30 for doses to liver and red bone marrow, and 40 for intakes: these uncertainties are not reflected in estimates of risk when point doses are used to assess them. It is also shown that better estimates of certain key HRTM absorption parameters could significantly reduce the uncertainties on lung dose in future studies.

Proposed genitalia contouring guidelines in anal cancer intensity-modulated radiotherapy.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) for anal canal carcinoma (ACC) is associated with favourable toxicity outcomes. Side effects include sexual dysfunction, skin desquamation, pain and fibrosis to perineum and genitalia region. The genitalia are situated anterior to the primary ACC between two inguinal regions providing a challenging structure to avoid. Techniques improving outcomes require robust, consistent genitalia contouring to ensure standardization and production of fully optimized IMRT plans. Official recommendations for genitalia contouring are lacking. We describe a potential genitalia contouring atlas for ACC radiotherapy. METHODS: Following a review of genitalia CT anatomy, a contouring atlas was generated for male and female patients positioned prone and supine. Particular attention was paid to the reproducibility of the genitalia contour in all planes. RESULTS: Male and female genitalia positioned prone and supine are described and represented visually through a contouring atlas. Contoured areas in males include penis and scrotum, and in females include clitoris, labia majora and minora. The muscles, bone, prostate, vagina, cervix and uterus should be excluded. The genitalia contour extends laterally to inguinal creases and includes areas of fat and skin anterior to the symphysis pubis for both genders. CONCLUSION: This atlas provides descriptive and visual guidance enabling more consistent genitalia delineation for both genders when prone and supine. The atlas can be used for other sites requiring radiotherapy planning. ADVANCES IN KNOWLEDGE: This atlas presents visual contouring guidance for genitalia in ACC radiotherapy for the first time. Contouring methods provide reproducible genitalia contours that allow the provision of accurate dose toxicity data in future studies.

An in vitro study comparing two dose regimes of fresh frozen plasma on conventional and thromboelastographic tests of coagulation after major hepatic resection.

BACKGROUND: After hepatic resection, post-operative increases in international normalised ratio (INR) are frequent, but rarely associated with bleeding complication. Coagulation as assessed by thrombin generation may be normal, despite the increased INR. This study tests the hypothesis that viscoelastic tests (VET) of coagulation remain normal, despite mild elevations in INR, examines the efficacy of fresh frozen plasma (FFP) in reversing prolongation of INR in such patients and determines the effect of FFP on VET. METHODS: A prospective cohort study of 47 patients undergoing major hepatectomy. In vitro spiking with FFP (7·5 and 15 mL kg(-1)) was carried out if post-operative day 2 (POD2) INR levels were ≥1·5. Thromboelastography (TEG®) and INR were measured before and after FFP spiking. RESULTS: Blood from patients with an INR ≥ 1·5 on POD2 was spiked with FFP. There was a significant reduction in the INR from 1·94 [standard deviation (SD): 0·59] to 1·46 (SD: 0·27, P = 0·005) and 1·36 (SD: 0·18, P = 0·0007) with FFP 7·5 or 15 mL kg(-1), respectively. At baseline, the TEG R-time [6·17 min (NR, 9-27 min)] and maximum amplitude (MA) [66·9 mm (NR, 44-64 mm)] were hypercoagulable, and remained so on POD2 for the R-time (6·7 min), but fell to within the normal range for the MA (54·0 mm). FFP spiking had no significant effect on TEG variables. CONCLUSIONS: Despite the rise in INR after hepatectomy, VET do not show evidence of hypocoagulability. In vitro addition of FFP had no significant effect on TEG parameters. Clinical use of FFP in this situation is questionable.

Management of paediatric tuberculosis in leading UK centres: unveiling consensus and discrepancies.

SETTING: Large specialist paediatric TB clinics in the UK. OBJECTIVE: To evaluate clinical practice and compare with national and international guidelines. DESIGN: A survey based on an electronic questionnaire on the management of latent tuberculous infection (LTBI) and tuberculosis (TB) disease was conducted in 13 specialist paediatric TB clinics. The consensus and discrepancies were evaluated by descriptive analysis. RESULTS: Practice was reportedly different when choosing age limits for preventive treatment for TB contacts with initially negative tuberculin skin tests (TSTs), interpretation of TST results and use of interferon-gamma release assays (IGRAs) in the context of LTBI. In relation to management of children with TB disease, practices varied for duration of treatment of osteoarticular TB, monitoring for ethambutol ocular toxicity and use of pyridoxine. There was limited experience with multidrug-resistant TB (MDR-TB), and over half of the clinics monitored MDR-TB contacts without giving preventive treatment. CONCLUSIONS: The survey showed heterogeneity in several aspects of clinical care for children with TB. Available paediatric TB guidelines differ substantially, explaining the wide variations in management of childhood TB. Prospective paediatric studies are urgently required to inform and standardise clinical practice, especially in the context of evolving drug resistance.

Evaluation of a rapid von Willebrand factor activity latex immuno assay for monitoring of patients with von Willebrand disease (VWD) receiving DDAVP or VWF replacement therapy.

Haemostatic management of surgery in patients with von Willebrand disease (VWD) includes DDAVP or von Willebrand factor (VWF)-containing concentrates. Although the recommendations are for monitoring by VWF activity assays, it is quite common for clinicians to use factor VIII due usually to longer turnaround times required for VWF ristocetin cofactor assay (VWF:RCo) measurements. The aim of this study was to evaluate use of the rapid HaemosIL VWF activity (VWF:Act) latex immuno assay (LIA) on an automated coagulometer (ACL TOP(™) 700; Instrumentation Laboratory, Bedford, MA, USA) compared to platelet-based VWF:RCo assays in this setting. One hundred and sixty-seven plasma samples from 42 patients [Type 1 (n = 22), Type 2A (n = 2), Type 2B (n = 3), Type 2M (n = 10), Type 3 (n = 3)] and acquired von Willebrand syndrome (n = 2) with VWD treated with DDAVP or VWF-containing concentrates were included in the study. Method comparison and method bias were evaluated by Bland-Altman analysis (BA) and Passing and Bablok regression modelling respectively. BA of baseline samples (n = 39) showed a mean difference of -3.0 (±1.96 SD -25.2 to +19.4). Post (treatment) samples (n = 120) were separated into two groups. Group 1 contained samples with VWF:RCo levels 10 to ≤175 IU dL(-1) (n = 97) and group 2, samples with VWF:RCo levels >175 IU dL(-1) (n = 23). BA of group 1 postsamples showed a mean difference of +3.4 (±1.96 SD -44.6 to +51.5), and the BA of Group 2 samples was -23.9 (±1.96 SD -136.1 to +88.3). In conclusion, use of HaemosIL VWF:Act LIA test on an automated coagulometer is a reproducible and rapid assay that can be used as an alternative test for monitoring VWF replacement therapy, facilitating dose adjustments on a real-time basis.