Case report: Hereditary angioedema in pregnancy.

Hereditary angioedema (HAE) is a rare genetic condition associated with episodic swelling due to dysfunction of bradykinin regulation pathways. This is most frequently caused by low level and/or function of the C1-esterase inhibitor protein (C1INH) which is known as hereditary angioedema with C1 inhibitor deficiency (C1INH-HAE). Pregnancy and labour can precipitate an attack, but the majority of women have an uncomplicated, spontaneous vaginal delivery. Intravenous C1INH is the first-line therapy in pregnancy and breastfeeding. It should be given if any obstetric intervention is planned. Routine prophylactic administration for uncomplicated vaginal birth is not mandatory but may be appropriate if symptoms recur frequently during the third trimester. Pregnant women with C1INH-HAE should deliver in a hospital with C1INH replacement, fiberoptic intubation and front-of-neck access equipment readily available. A documented treatment plan should be developed within a multi-disciplinary team to pre-empt complications. We describe a case of C1INH-HAE diagnosed in pregnancy.

Implementation of vaginal preparation prior to caesarean section.

INTRODUCTION: Surgical site infections following caesarean section are associated with significant morbidity. Vaginal preparation is the cleansing of the vaginal epithelium with an antibacterial solution to reduce the bacterial load and therefore reduce ascending genital tract infection. It is recommended by the WHO and a Cochrane review in 2018 concluded that vaginal preparation immediately before caesarean section probably reduces the rates of postoperative endometritis. OBJECTIVE: To implement vaginal preparation prior to caesarean section at Guy's and St Thomas' Hospital NHS Foundation Trust and reduce rates of deep surgical site infections. METHODS: The protocol (included within the appendices) for vaginal preparation prior to caesarean section was developed after reviewing the available evidence. Two vaginal preparation champions, a midwife and a scrub nurse, were selected to help promote and assist in the implementation. The first implementation cycle included elective and category II and III caesarean sections. To ensure acceptability, 20 women were asked to complete a questionnaire following vaginal preparation. Once the intervention was being performed in >85% of eligible women, the inclusion criteria was expanded to include category I caesarean sections. RESULTS: Twelve months following implementation, vaginal preparation was still being performed in 89% of eligible women. The deep surgical site infection rate is now the lowest recorded in the last 6 years. Vaginal preparation prior to caesarean section was acceptable to pregnant women and no adverse effects were reported. CONCLUSIONS: Vaginal preparation prior to caesarean section has been successfully implemented at Guy's and St Thomas' Hospital NHS Foundation Trust. This simple, cheap intervention, performed with readily available materials, is still being performed in a high number of caesarean sections 12 months post-implementation. It has resulted in a reduction in deep surgical site infections. Involvement of key stakeholders and the recruitment of vaginal preparation champions were key to success.

Obstetric medical care and training in the United Kingdom.

The UK confidential enquiry into maternal deaths identified poor management of medical problems in pregnancy to be a contributory factor to a large proportion of indirect maternal deaths. Maternal (obstetric) medicine is an exciting subspecialty that encompasses caring for both women with pre-existing medical conditions who become pregnant, as well as those who develop medical conditions in pregnancy. Obstetrics and gynaecology trainees have some exposure to maternal medicine through their core curriculum and can then complete an advanced training skills module, subspecialise in maternal-fetal medicine or take time out to complete the Royal College of Physicians membership examination. Physician training has limited exposure to medical problems in pregnancy and has therefore prompted expansion of the obstetric physician role to ensure physicians with adequate expertise attend joint physician-obstetrician clinics. This article describes the role of an obstetric physician in the UK and the different career pathways available to physicians and obstetricians interested in maternal medicine.

Prospective cohort study of procalcitonin levels in children with cancer presenting with febrile neutropenia.

BACKGROUND: Febrile neutropenia (FNP) causes significant morbidity and mortality in children undergoing treatment for cancer. The development of clinical decision rules to help stratify risks in paediatric FNP patients and the use of inflammatory biomarkers to identify high risk patients is an area of recent research. This study aimed to assess if procalcitonin (PCT) levels could be used to help diagnose or exclude severe infection in children with cancer who present with febrile neutropenia, both as a single measurement and in addition to previously developed clinical decision rules. METHODS: This prospective cohort study of a diagnostic test included patients between birth and 18 years old admitted with febrile neutropenia to the Paediatric Oncology and Haematology Ward in Leeds between 1st October 2012 and 30th September 2013. Each admission with FNP was treated as a separate episode. Blood was taken for a procalcitonin level at admission with routine investigations. 'R' was used for statistical analysis. Likelihood ratios were calculated and multivariable logistic regression. RESULTS: Forty-eight episodes from 27 patients were included. PCT >2 ng/dL was strongly associated with increased risk of severe infection (likelihood ratio of 26 [95% CI 3.5, 190]). The data suggests that the clinical decision rules are largely ineffective at risk stratification, frequently over-stating the risk of individual episodes. High procalcitonin levels on admission are correlated with a greatly increased risk of severe infection. CONCLUSIONS: This study does not show a definitive benefit in using PCT in FNP though it supports further research on its use. The benefit of novel biomarkers has not been proven and before introducing new tests for patients it is important their benefit above existing features is proven, particularly due to the increasing importance of health economics.

Arterio-Venous Fistula: Is it Critical for Prolonged Survival in the over 80's Starting Haemodialysis?

BACKGROUND: Dialysis in elderly patients (>80-years-old) carries a poor prognosis, but little is known about the most effective vascular access method in this age group. An arteriovenous fistula (AVF) is both time-consuming and initially expensive, requiring surgical insertion. A central venous catheter (CVC) is initially a cheaper alternative, but carries a higher risk of infection. We examined whether vascular access affected 1-year and 2-year mortality in elderly patients commencing haemodialysis. METHODS: Initial vascular access, demographic and survival data for elective haemodialysis patients >80-years was collated using regional databases. A cohort of conservatively managed patients was included for comparison. A log-rank test was used to compare survival between groups and a chi-square test was used to compare 1-year and 2-year survival. RESULTS: 167 patients (61% male) were included: CVC (101), AVF (25) and conservative management (41). Mean age (median) of starting haemodialysis (eGFR ≤10mL/min/1.73m2): CVC; 83.4 (2.3) and AVF; 82.3 (1.8). Mean age of conservatively managed patients reaching an eGFR ≤10mL/min/1.73m2 was 85.8 (3.6). Mean (median) survival on dialysis was 2.2 (1.8) years for AVF patients, 2.1 (1.2) for CVC patients, and 1.5 (0.9) for conservatively managed patients (p = 0.107, controlling for age/sex p = 0.519). 1-year and 2-year mortality: AVF (28%/52%); CVC (49%/57%), and conservative management (54%/68%). There was no significant difference between the groups at 1-year (p = 0.108) or 2-years (p = 0.355). CONCLUSION: These results suggest that there is no significant survival benefit over a 2-year period when comparing vascular access methods. In comparison to conservative management, survival benefit was marginal. The decision of whether and how (choice of their vascular access method) to dialysis the over 80s is multifaceted and requires a tailored, multidisciplinary approach.

Breast cancer-related lymphoedema and venepuncture: a review and evidence-based recommendations.

Lymphoedema is a recognised complication of axillary surgery in women with early breast cancer. Such women are widely advised to avoid venepuncture on the ipsilateral side lest this cause complications including lymphoedema. This can lead to multiple failed venepuncture attempts causing distress to both patient and healthcare professional. We reviewed current guidelines and critically appraised the evidence relating the development of lymphoedema to venepuncture to educate healthcare professionals and develop evidence-based guidelines. A systematic search of bibliographic databases was performed and an Internet search undertaken to identify patient information leaflets from societies and support groups. Seven published articles were identified together with 15 published patient information leaflets. Only one small prospective study was identified (level of evidence 2), the remainder being case-control studies (level 3) or retrospective reviews (level 4). There is no good evidence that venepuncture can precipitate lymphoedema. New, patient-centred, evidence-based recommendations for venepuncture in women with breast cancer are proposed. Whenever possible, venepuncture should be performed on the contralateral arm. If this is not readily achieved, in the absence of lymphoedema it is preferable to consider venepuncture in the ipsilateral arm or insertion of a central venous device than to make further attempts in the contralateral arm or resort to sites such as veins in the foot. In the absence of lymphoedema, venesection in the ipsilateral arm carries little, if any, risk of additional complications. We offer evidence-based, patient-centred guidelines for venepuncture in patients with breast cancer following an axillary intervention.

Systematic review of definitions of failure in revisional bariatric surgery.

BACKGROUND: There are no agreed definitions as to what constitutes a 'failure' of the primary bariatric procedure in relation to weight loss. METHODS: The MEDLINE database for primary research articles was searched using obesity [title] or bariatric [title] and revision [title] or revisional [title]. RESULTS: The MEDLINE search retrieved 174 studies. After duplicates and exclusions were removed, 60 articles underwent analysis. Fifty-one studies included inadequate weight loss or weight regain as an indication for revision: 31/51 (61 %) gave no definition of failure, 7/20 quoted <50 % of excess weight loss at 18 months and 6/20 used <25 % excess weight loss. CONCLUSIONS: The majority of published studies do not define failure of bariatric surgery, and <50 % excess weight loss at 18 months was the most frequent definition identified.

Critical Review of Clinical Practice Guidelines for Fertility Preservation in Teenagers and Young Adults with Cancer.

Purpose: The 5-year survival of teenagers and young adults (TYAs; 13-24 years old) with cancer has continued to rise, but as a result more patients experience late effects of treatment, such as infertility. Advice regarding fertility preservation in relation to cancer is provided in numerous clinical practice guidelines, but the rigor of their development is unclear. Methods: A systematic search was undertaken for clinical practice guidelines regarding fertility preservation in TYAs with cancer. All guidelines were reviewed according to the Appraisal of Guidelines for Research and Evaluation (AGREE-II) criteria. Five out of 13 identified guidelines scored over 75% in the "rigor of development" section and were further appraised. Content, scope, and consistencies between recommendations were also examined. Results: All five of the reviewed guidelines encouraged oncologists to have discussions with their patients about potential fertility issues associated with treatment and available fertility preservation methods. The cryopreservation of sperm, oocytes, and embryos were all recommended as first-line interventions in postpubertal patients. Recommendations surrounding pre- or peripubescent adolescents were few, with many techniques only recommended as part of a clinical trial. The risk of subfertility associated with different treatment regimens was poorly described. Conclusions: The methodology and development of guidelines describing fertility preservation in TYA cancer patients varied greatly. Methodological quality did not clearly influence key recommendations. Those involved with the development of guidelines are encouraged to clearly define their development methods to allow users to be confident of the quality.

A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response.

Reports from individual centres suggest a preponderance of females with chronic cough. Females also have heightened cough reflex sensitivity. Here we have reviewed the age and sex of unselected referrals to 11 cough clinics. To investigate the cause of any observed sex dimorphism, functional magnetic resonance imaging of putative cough centres was analysed in normal volunteers. The demographic profile of consecutive patients presenting with chronic cough was evaluated. Cough challenge with capsaicin was undertaken in normal volunteers to construct a concentration-response curve. Subsequent functional magnetic resonance imaging during repeated inhalation of sub-tussive concentrations of capsaicin observed areas of activation within the brain and differences in the sexes identified. Of the 10,032 patients presenting with chronic cough, two-thirds (6591) were female (mean age 55 years). The patient profile was largely uniform across centres. The most common age for presentation was 60-69 years. The maximum tolerable dose of inhaled capsaicin was lower in females; however, a significantly greater activation of the somatosensory cortex was observed. Patients presenting with chronic cough from diverse racial and geographic backgrounds have a strikingly homogeneous demographic profile, suggesting a distinct clinical entity. The preponderance of females may be explained by sex-related differences in the central processing of cough sensation.

Applications of coxsackievirus A21 in oncology.

The clinical management of cancer continues to be dominated by macroscopic surgical resection, radiotherapy, and cytotoxic drugs. The major challenge facing oncology is to achieve more selective, less toxic and effective methods of targeting disseminated tumors, a challenge oncolytic virotherapy may be well-placed to meet. Characterization of coxsackievirus A21 (CVA21) receptor-based mechanism of virus internalization and lysis in the last decade has suggested promise for CVA21 as a virotherapy against malignancies which overexpress those receptors. Preclinical studies have demonstrated proof of principle, and with the results of early clinical trials awaited, CVA21 may be one of the few viruses to demonstrate benefit for patients. This review outlines the potential of CVA21 as an oncolytic agent, describing the therapeutic development of CVA21 in preclinical studies and early stage clinical trials. Preclinical evidence supports the potential use of CVA21 across a range of malignancies. Malignant melanoma is the most intensively studied cancer, and may represent a "test case" for future development of the virus. Although there are theoretical barriers to the clinical utility of oncolytic viruses like CVA21, whether these will block the efficacy of the virus in clinical practice remains to be established, and is a question which can only be answered by appropriate trials. As these data become available, the rapid journey of CVA21 from animal studies to clinical trials may offer a model for the translation of other oncolytic virotherapies from laboratory to clinic.