Prognostic implications of histological tumor regression (Böhm's score) in patients receiving neoadjuvant chemotherapy for high grade serous tubal & ovarian carcinoma.

OBJECTIVE: Primary objective of this study was to determine prognostic significance of Bohm's histopathological regression score in patients who received neoadjuvant chemotherapy (NACT) for treatment of high grade serous (HGS) tubal & ovarian carcinoma. METHODS: This was a retrospective cohort study of patients who received NACT between 2010 and 2015. The 3 point histopathological regression score of Böhm was used to classify chemotherapy response. Survival outcomes between the 3 different subgroups was analysed and compared with standard clinico-pathological variables using the Cox proportional hazards model and log-rank test. RESULTS: Study cohort comprised 111 patients. Chemotherapy response score (CRS) 3 was observed in 47 (42.4%) and CRS 1and CRS 2 in 22 (19.8%) and 42 (37.8%) women respectively. Women with CRS score of 1 and 2 combined showed a three-fold increased risk of progression on both univariate and multivariate assessment (HR 3.54; C.I 2.19-5.72, p < 0.001). The median overall survival for patients with CRS 1 was 34 months, CRS 2 was 30 months and 47 months for CRS 3. CRS 1 and 2 combined was the only variable that held significance in prediction of reduced overall survival on multivariate assessment (HR 3.26, C.I 1.91-5.54, p 0.0006). CRS 1 and 2 were also associated with 5.15-fold increased risk of relapse within 6 months of completion of chemotherapy (Odds ratio OR 5.15, C.I 0.07-0.47, p - 0.002). CONCLUSION: CRS is an independent prognosticator of survival and reliable predictor of relapse within 6 months in advanced high grade serous tubal and ovarian carcinoma patients receiving NACT.

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.

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.

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.

Case report: Guillain-Barré syndrome following renal transplantation--a diagnostic dilemma.

BACKGROUND: Guillain-Barré syndrome (GBS) is an acute polyneuropathy caused by an autoimmune response towards a foreign antigen, notably viral infections. It is characterised by a symmetrical ascending paralysis with treatment remaining largely supportive; however, plasma exchange or intravenous immunoglobulins can be used to shorten recovery time. CASE REPORT: We describe a case of severe acute GBS in a patient post-renal transplantation. The 44-year-old gentleman's induction therapy consisted of methyl prednisolone and basiliximab, with subsequent tacrolimus and mycophenolate mofetil as immunosuppressive agents. Tacrolimus was discontinued immediately on suspicion of a temporal relationship with the patient's condition, and substituted with a combination of ciclosporin, mycophenolate mofetil and prednisolone. Due to extensive patient screening prior to transplant, negative virology/immunology and normal nerve biopsy findings, both tacrolimus and basiliximab may be indicated as causative agents. CONCLUSION: Immunosuppressive-induced GBS should be considered a differential diagnosis in patients on tacrolimus or basiliximab with acute-onset limb weakness, especially if recently commenced. Discontinuation of tacrolimus and initiation of plasma exchange for the treatment for tacrolimus-associated GBS may be beneficial.

Reducing laboratory costs through rational testing in suspected pre-eclampsia.

The current electronic laboratory order set at Epsom and St Helier University Hospitals NHS Trust for suspected pre-eclampsia includes a full blood count, urea and electrolytes, liver function, gamma-glutamyltransferase and uric acid. Local and national guidelines do not recommend the use of gamma-glutamyltransferase or uric acid for the investigation or monitoring of pre-eclampsia, as they are poor predictors of maternal and neonatal outcomes. We aimed to remove the automatic inclusion of gamma-glutamyltransferase and uric acid from the electronic laboratory order set for suspected pre-eclampsia. Stakeholders were approached to gain an understanding of whether gamma-glutamyltransferase and uric acid were being used in the clinical assessment of suspected pre-eclampsia. Obstetric consultants and maternity staff confirmed that they do not use uric acid in their clinical assessment, despite the laboratory phoning with abnormal results. In addition, an isolated gamma-glutamyltransferase rise is of no particular significance and is not part of the National Institute for Health and Care Excellence (NICE) diagnostic criteria for pre-eclampsia. The baseline number of gamma-glutamyltransferase and uric acid requests from the maternity department was identified over 2 months. The hospital information technology service was then asked to remove gamma-glutamyltransferase and uric acid from the electronic laboratory order set. The number of gamma-glutamyltransferase and uric acid requests from the maternity department following the intervention was identified over 2 months. A significant reduction in both gamma-glutamyltransferase and uric acid requests were noted. In addition, the midwives within the maternity assessment unit noted a significant reduction in phone calls from the laboratory to escalate abnormal blood results. This has saved the trust money and reduced staff time answering phone calls regarding abnormal blood results. A repeat assessment at 8 months following the removal of gamma-glutamyltransferase and uric acid demonstrated sustainability of the project.

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.

Validation of the BPro radial pulse waveform acquisition device in pregnancy and gestational hypertensive disorders.

OBJECTIVE: To validate the BPro blood pressure (BP) wrist device for use in pregnancy and preeclampsia according to the Universal Standard protocol. PARTICIPANTS AND METHODS: BP was measured sequentially in 45 pregnant women (including 15 with preeclampsia, 15 with gestational hypertension and 15 who remained normotensive) alternating between a mercury sphygmomanometer and BPro device. RESULTS: The BPro is accurate in pregnancy with a mean device-observer difference of -1.7 ± 6.1 and 0.1 ± 4.6 mmHg for SBP and DBP, respectively. In women with preeclampsia, BPro also met the validation criteria for the Universal Standard protocol with a mean device-observer difference of -2.7 ± 7.1 and 0.3 ± 4.7 mmHg for SBP and DBP, respectively. However, the number of absolute BP differences within 5 mmHg was considerably fewer in those with preeclampsia when compared to the other two subgroups. CONCLUSION: The BPro device can be recommended for BP measurement in pregnancy but should be used with caution in those with confirmed preeclampsia.

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.

Birth weight in pregnancies complicated by maternal heart disease.

OBJECTIVE: To assess median and percentile birthweight distribution in women with various groups of heart disease relative to a contemporaneous comparison group. METHODS: Data on birth weight and gestational age were collected from 1321 pregnancies ≥24 weeks' gestation in 1053 women with heart disease from seven UK maternity units. Women were assigned to one of 16 groups according to their cardiac lesion. In units where it was possible, data on two births, one delivering before and one after index cases, were collected, giving 2307 comparators. Birthweight percentiles (corrected for gestational age, sex and parity) were calculated using Aberdeen norms. We assessed the association of birth weight with cardiac lesion, maternal hypoxaemia (saturations <90%), systemic ventricular function and beta-blockers. RESULTS: 1321 pregnancies in women with heart disease and 2307 comparators were studied. Almost all groups with heart disease had lower median and percentile birth weights than comparators, significantly in 10 groups, the biggest effect seen in women with Fontan circulation, pulmonary hypertension, prosthetic heart valves, systemic right ventricle, Marfan syndrome, repaired tetralogy of Fallot and cardiomyopathy (in that order). In 307 pregnancies, women took beta-blockers; median birth weight adjusted for maternal age, parity and the effect of the cardiac lesion was 3116.7 g (IQR 790.4) when beta-blockers were used and 3354.3 g (IQR 634.1) when they were not (p<0.001). 17 women had saturations <90%, and median birth weight was significantly lower, 3105.4 g (IQR 1288.9) versus 3387.7 g (IQR 729.8) (p=0.006). CONCLUSION: Our findings identify specific groups of women with heart disease at risk of having a small baby.

Retrospective UK multicentre study of the pregnancy outcomes of women with a Fontan repair.

BACKGROUND: The population of women of childbearing age palliated with a Fontan repair is increasing. The aim of this study was to describe the progress of pregnancy and its outcome in a cohort of patients with a Fontan circulation in the UK. METHODS: A retrospective study of women with a Fontan circulation delivering between January 2005 and November 2016 in 10 specialist adult congenital heart disease centres in the UK. RESULTS: 50 women had 124 pregnancies, resulting in 68 (54.8%) miscarriages, 2 terminations of pregnancy, 1 intrauterine death (at 30 weeks), 53 (42.7%) live births and 4 neonatal deaths. Cardiac complications in pregnancies with a live birth included heart failure (n=7, 13.5%), arrhythmia (n=6, 11.3%) and pulmonary embolism (n=1, 1.9%). Very low baseline maternal oxygen saturations at first obstetric review were associated with miscarriage. All eight women with saturations of less than 85% miscarried, compared with 60 of 116 (51.7%) who had baseline saturations of ≥85% (p=0.008). Obstetric and neonatal complications were common: preterm delivery (n=39, 72.2%), small for gestational age (<10th percentile, n=30, 55.6%; <5th centile, n=19, 35.2%) and postpartum haemorrhage (n=23, 42.6%). There were no maternal deaths in the study period. CONCLUSION: Women with a Fontan circulation have a high rate of miscarriage and, even if pregnancy progresses to a viable gestational age, a high rate of obstetric and neonatal complications.

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.

Renal tubular acidosis type 4 in pregnancy.

We describe the clinical course of renal tubular acidosis (RTA) type 4 in pregnancy, which has not been previously published. Renal tubular acidosis type 4 is a condition associated with increased urinary ammonia secondary to hypoaldosteronism or pseudohypoaldosteronism. Pregnancy may worsen the hyperkalaemia and acidosis of renal tubular acidosis type 4, possibly through an antialdosterone effect. We advise regular monitoring of potassium and pH throughout pregnancy to ensure safe levels are maintained.

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.

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.

Improving mid stream urine sampling: reducing labelling error and laboratory rejection.

A urine sample is vital in older patients with pyrexia or acute confusion, and commonly directs clinicians towards a source of infection. Not only can the organism be identified, but sensitivities to antibiotics can also guide prescribing. A high number of urine samples were not being processed on the medicine for older people wards at St. James's Hospital due to incomplete hand-written request forms not complying with trust policy. Previous attempts to re-educate staff had failed to improve acceptance rates. Rejected samples delay diagnosis, identification of organisms and subsequent sensitivities, as well as increasing staff workload. A total of 72 urine samples were audited from our wards in March 2013; 12 (17%) rejected. Clinicians were notified of rejected samples within one to four days. An electronic-requesting system was implemented in April 2013. Once implemented, a further two data collection cycles of 72 urine samples were completed from the same wards. In December 2013, 55 (76%) were electronically requested and 17 (24%) hand-written. Four (5%) samples were rejected and were all hand-written. In August 2014, 61 (85%) were electronically requested and 11 (15%) hand-written. No samples were rejected. The electronic-requesting system has effectively reduced the number of rejected urine samples. No electronically requested samples were rejected, therefore 100% sample acceptance is achievable. It is more effective than re-educating staff alone and ensures requests meet trust policy. Clinicians were notified of a samples rejection after one to four days. By this time patients may have started antibiotic therapy, decreasing the likelihood of isolating the causative organism in subsequent samples. All urine samples requested must meet a high standard and comply with trust policy in order to be processed. An electronic-requesting system removes errors of omission and ensures policy compliance, ultimately leading to improved patient care. Now our processes are reliable we will go onto measure changes at patient level, e.g. confirmed diagnoses of urine infection, outcomes of earlier narrow spectrum antibiotics, and length of stay.

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.