CAnceR IN PreGnancy (CARING) - a retrospective study of cancer diagnosed during pregnancy in the United Kingdom.

BACKGROUND: The incidence of cancer diagnosed during pregnancy is increasing. Data relating to investigation and management, as well as maternal and foetal outcomes is lacking in a United Kingdom (UK) population. METHODS: In this retrospective study we report data from 119 patients diagnosed with cancer during pregnancy from 14 cancer centres in the UK across a five-year period (2016-2020). RESULTS: Median age at diagnosis was 33 years, with breast, skin and haematological the most common primary sites. The majority of cases were new diagnoses (109 patients, 91.6%). Most patients were treated with radical intent (96 patients, 80.7%), however, gastrointestinal cancers were associated with a high rate of palliative intent treatment (63.6%). Intervention was commenced during pregnancy in 68 (57.1%) patients; 44 (37%) had surgery and 31 (26.1%) received chemotherapy. Live births occurred in 98 (81.7%) of the cases, with 54 (55.1%) of these delivered by caesarean section. Maternal mortality during the study period was 20.2%. CONCLUSIONS: This is the first pan-tumour report of diagnosis, management and outcomes of cancer diagnosed during pregnancy in the UK. Our findings demonstrate proof of concept that data collection is feasible and highlight the need for further research in this cohort of patients.

Splenic artery pseudoaneurysm causing delayed gastrointestinal bleeding after gastrocolonic fistula following sleeve gastrectomy.

Delayed gastrointestinal bleeding in the context of a gastric fistula is a very rare complication of longitudinal sleeve gastrectomy. We report the case of a patient who presented with massive gastrointestinal bleeding from a pseudoaneurysm arising from the splenic artery following complications after a longitudinal sleeve gastrectomy several months previously. The case was successfully managed with angiographic embolisation and we present our experience with recommendations for managing this rare but life-threatening complication.

Atrial fibrillation is associated with cognitive decline in stroke-free subjects: the Tromsø Study.

BACKGROUND AND PURPOSE: Previous studies have shown associations between atrial fibrillation (AF) and cognitive decline. We investigated this association in a prospective population study, focusing on whether stroke risk factors modulated this association in stroke-free women and men. METHODS: We included 4983 participants (57% women) from the fifth survey of the Tromsø Study (Tromsø 5, 2001), of whom 2491 also participated in the sixth survey (Tromsø 6, 2007-2008). Information about age, education, blood pressure, body mass index, lipids, smoking, coffee consumption, physical activity, depression, coronary and valvular heart disease, heart failure and diabetes was obtained at baseline. AF status was based on hospital records. The outcome was change in cognitive score from Tromsø 5 to Tromsø 6, measured by the verbal memory test, the digit-symbol coding test and the tapping test. RESULTS: Mean age at baseline was 65.4 years. The mean reduction in the tapping test scores was significantly larger in participants with AF (5.3 taps/10 s; 95% CI: 3.9, 6.7) compared with those without AF (3.8 taps/10 s; 95% CI: 3.5, 4.1). These estimates were unchanged when adjusted for other risk factors and were similar for both sexes. AF was not associated with change in the digit-symbol coding or the verbal memory tests. CONCLUSION: Atrial fibrillation in stroke-free participants was independently associated with cognitive decline as measured with the tapping test.

Keraring implantation using the Zeiss Visumax femtosecond laser in the management of patients with keratoconus.

PurposeTo evaluate the safety and efficacy of implanted Kerarings in patients with mild, moderate, and severe keratoconus.Patients and methodsA 12-month retrospective case series of 70 eyes of 70 patients who underwent Keraring implantation with the Zeiss Visumax femtosecond laser. Patients were stratified into three groups according to their topography as mild (mean K <48 D) moderate (48-55 D) or severe (>55 D). Main outcome measures were visual acuity, manifest refraction, and corneal topography. Complications were recorded.ResultsA total of 66 patients completed the 12-month follow-up. In all, 4 rings were explanted, 3 due to no improvement in visual function and 1 due to corneal neovascularization. Also, 4 rings were repositioned. In mild disease (n=28), BCVA increased to 0.10 logMAR, sphere decreased to -1.54 D, cylinder decreased to 2.54 D, Kmax decreased to 46.25 D, and keratometric astigmatism to 3.88 D (P<0.01 for each compared with preoperative values). No patients lost vision. In moderate disease (n=27), sphere decreased to -4.06 D, cylinder decreased to 3.47 D, Kmax decreased to 51.69 D, and keratometric astigmatism to 4.56 D (P<0.05 for each compared with preoperative values). In severe disease (n=11), BCVA increased to 0.34 logMAR, Kmax decreased to 57.65 D, and keratometric astigmatism to 5.07 D (P<0.05 for each compared with preoperative values).ConclusionFemtosecond laser-assisted Keraring implantation is a safe and minimally invasive treatment option to improve the refraction and visual function in patients with keratoconus. Patients with mild keratoconus are more likely to have a favourable outcome following Keraring implantation.

Effectiveness of a care bundle to reduce surgical site infections in patients having open colorectal surgery.

Introduction In 2010 a care bundle was introduced by the Department of Health (DH) to reduce surgical site infections (SSIs) in England. To date, use of the care bundle has not been evaluated despite incorporating interventions with resource implications. The aim of this study was to evaluate the DH SSI care bundle in open colorectal surgery. Methods A prospective cohort design was used at two teaching hospitals in England. The baseline group consisted of 127 consecutive patients having colorectal surgery during a 6-month period while the intervention group comprised 166 patients in the subsequent 6 months. SSI and care bundle compliance data were collected using dedicated surveillance staff. Results Just under a quarter (24%) of the patients in the baseline group developed a SSI compared with just over a quarter (28%) in the care bundle group (p>0.05). However, compliance rates with individual interventions, both before and after the implementation of the bundle, were similar. Interestingly, in only 19% of cases was there compliance with the total care bundle. The single intervention that showed an associated reduction in SSI was preoperative warming (p=0.032). Conclusions The DH care bundle did not reduce SSIs after open colorectal surgery. Despite this, it is not possible to state that the bundle is ineffective as compliance rates before and after bundle implementation were similar. All studies evaluating the effectiveness of care bundles must include data for compliance with interventions both before and after implementation of the care bundle; poor compliance may be one of the reasons for the lower than expected reduction of SSIs.

Cardiac complications associated with goal-directed therapy in high-risk surgical patients: a meta-analysis.

Patients with limited cardiopulmonary reserve are at risk of mortality and morbidity after major surgery. Augmentation of oxygen delivery index (DO2I) with i.v. fluids and inotropes (goal-directed therapy, GDT) has been shown to reduce postoperative mortality and morbidity in high-risk patients. Concerns regarding cardiac complications associated with fluid challenges and inotropes may prevent clinicians from performing GDT in patients who need it most. We hypothesized that GDT is not associated with an increased risk of cardiac complications in high-risk, non-cardiac surgical patients. We performed a systematic search of Medline, Embase, and CENTRAL databases for randomized controlled trials (RCTs) of GDT in high-risk surgical patients. Studies including cardiac surgery, trauma, and paediatric surgery were excluded. We reviewed the rates of all cardiac complications, arrhythmias, myocardial ischaemia, and acute pulmonary oedema. Meta-analyses were performed using RevMan software. Data are presented as odds ratios (ORs), [95% confidence intervals (CIs)], and P-values. Twenty-two RCTs including 2129 patients reported cardiac complications. GDT was associated with a reduction in total cardiovascular (CVS) complications [OR=0.54, (0.38-0.76), P=0.0005] and arrhythmias [OR=0.54, (0.35-0.85), P=0.007]. GDT was not associated with an increase in acute pulmonary oedema [OR=0.69, (0.43-1.10), P=0.12] or myocardial ischaemia [OR=0.70, (0.38-1.28), P=0.25]. Subgroup analysis revealed the benefit is most pronounced in patients receiving fluid and inotrope therapy to achieve a supranormal DO2I, with the use of minimally invasive cardiac output monitors. Treatment of high-risk surgical patients GDT is not associated with an increased risk of cardiac complications; GDT with fluids and inotropes to optimize DO2I during early GDT reduces postoperative CVS complications.

HIV-1 co-receptor expression and epithelial immune cells of the cervix in asymptomatic women attending a genitourinary medicine clinic.

OBJECTIVES: The aim of the study was to qualitatively and semiquantitatively characterize the expression of the principal HIV co-receptors chemokine (C-C motif) receptor 5 (CCR5) and chemokine (C-X-C motif) receptor 4 (CXCR4) on susceptible CD4 T-helper cell, monocyte/macrophage and Langerhans dendritic cell populations within the cervical epithelia of asymptomatic women attending a genitourinary medicine clinic. METHODS: Of 77 asymptomatic women recruited, 35 were excluded: 21 because they were found to have bacterial vaginosis, eight because they were found to have candida and six for other reasons. Cervical cytobrush samples from 11 women with Chlamydia trachomatis infection and 31 women without any detectable genital infection were stained with fluorescently labelled antibodies specific for cell surface CCR5, CXCR4, CD4, CD3, CD1a and CD19 expression, then analysed by flow cytometry. RESULTS: CD4/CD3 T-helper cells (84%), CD1a Langerhans dendritic cells (75%) and CD4/CD14 monocytes/macrophages (59%) were detected in the samples. CCR5 and CXCR4 HIV co-receptor expression was observed on 46-86% of the above subsets. CD1a cells exhibited significantly higher CCR5 and CXCR4 positivity and median fluorescence than CD4 cells and higher CXCR4 positivity and median fluorescence than CD14 cells (P < 0.05 or less). Increased detection of CCR5 over CXCR4 was seen in CD14 cells (P < 0.05). No significant differences in CCR5 or CXCR4 expression were found in samples from asymptomatic women with or without chlamydial infection. CONCLUSIONS: Co-receptor expression confirms the potential for CD1a Langerhans cells, monocytes/macrophages and T-helper cells in the cervix as primary targets for HIV infection. Previously observed selective transmission of CCR5-tropic isolates cannot be accounted for by a lack of CXCR4-expressing CD4 cervical immune cells. We were unable to identify any specific impact of chlamydial infection on co-receptor expression in this study.

A two-event in vitro model of acute chest syndrome: the role of secretory phospholipase A2 and neutrophils.

BACKGROUND: Acute chest syndrome (ACS) in sickle cell disease is associated with elevation of secretory phospholipase A(2) (sPLA(2) ). We hypothesize that sPLA(2) cleaves membrane lipids from sickled red blood cells (RBCs) causing PMN-mediated endothelial cell injury (ECI) as the second event in a two-event model. METHODS: Whole blood was collected from children when in steady state or daily during admissions for vaso-occlusive pain (VOC) or ACS. The plasma and RBCs were separated, sPLA(2) levels were measured, and the RBCs were incubated with sPLA(2) . Plasma and lipids, extracted from the plasma or the supernatant of sPLA(2) -treated RBCs, were assayed for PMN priming activity and used as the second event in a model of PMN-mediated ECI. Phosphatidylserine (PS) surface expression on RBCs was quantified by flow cytometry. RESULTS: Increased sPLA(2) -IIa levels were associated with ACS. SPLA(2) -liberated lipids from VOC and the plasma, plasma lipids and sPLA(2) -liberated lipids from ACS primed PMNs and caused PMN-mediated ECI (P < 0.01). RBCs from VOC had increased in PS surface expression versus steady state. CONCLUSIONS: ACS plasma and lipids and sPLA(2) -released lipids from RBCs during VOC or ACS induce PMN-mediated ECI. VOC elicited increases in PS surface expression providing a membrane substrate for sPLA(2) lysis of sickle RBCs.

Transfusion-related acute lung injury (TRALI): current concepts and misconceptions.

Transfusion-related acute lung injury (TRALI) is the most common cause of serious morbidity and mortality due to hemotherapy. Although the pathogenesis has been related to the infusion of donor antibodies into the recipient, antibody negative TRALI has been reported. Changes in transfusion practices, especially the use of male-only plasma, have decreased the number of antibody-mediated cases and deaths; however, TRALI still occurs. The neutrophil appears to be the effector cell in TRALI and the pathophysiology is centered on neutrophil-mediated endothelial cell cytotoxicity resulting in capillary leak and ALI. This review will detail the pathophysiology of TRALI including recent pre-clinical data, provide insight into newer areas of research, and critically assess current practices to decrease it prevalence and to make transfusion safer.

Post-discharge surveillance to identify colorectal surgical site infection rates and related costs.

A growing number of surveillance studies have highlighted concerns with relying only on data from inpatients. Without post-discharge surveillance (PDS) data, the rate and burden of surgical site infections (SSIs) are underestimated. PDS data for colorectal surgery in the UK remains to be published. This is an important specialty to study since it is considered to have the highest SSI rate and is among the most expensive to treat. This study of colorectal SSI used a 30 day surveillance programme with telephone interviews and home visits. Each additional healthcare resource used by patients with SSI was documented and costed. Of the 105 patients who met the inclusion criteria and completed the 30 day follow-up, 29 (27%) developed SSI, of which 12 were diagnosed after discharge. The mean number of days to presentation of SSI was 13. Multivariable logistic analysis identified body mass index as the only significant risk factor. The additional cost of treating each infected patient was pound sterling 10,523, although 15% of these additional costs were met by primary care. The 5 month surveillance programme cost pound sterling 5,200 to run. An analysis of the surveillance nurse's workload showed that the nurse could be replaced by a healthcare assistant. PDS to detect SSI after colorectal surgery is necessary to provide complete data with accurate additional costs.

Association of antibodies to hepatitis C virus glycoproteins 1 and 2 (anti-E1E2) with HCV disease.

Hepatitis C virus (HCV) causes acute and chronic liver diseases in humans. Its two envelope glycoproteins, E1 and E2, provide a target for host immune recognition. HCV genotypes are classified into six genetic groups. To study the role of anti-HCV E1 and E2 (anti-E1E2) in HCV disease, the correlation between antibody level and viral load, genotype, disease severity and response to treatment was investigated. The levels of antibodies to HCV glycoproteins E1 and E2 antibodies were evaluated in 230 sera of patients with chronic hepatitis C by enzyme-linked immunosorbent assay. The antigens used were recombinant HCV glycoproteins derived from genotype 1 (H77c) and genotype 3 (UKN3A1.28). Seroreactivity was greater when sera were tested against antigen derived from their homologous genotype than against heterologous antigen. Reactivity against UKN3A1.28 in sera from patients infected with genotype 3 was significantly higher than corresponding reactivity between patients infected with genotype 1 and H77c. The seroreactivity was inversely proportional to the viral load and to the degree of liver fibrosis. The pre-treatment level of anti-E1E2 was higher in sustained responders to combination therapy. These results demonstrate that seroreactivity against E1E2 depends upon the genotypic origin of the E1E2 antigens and the infecting genotype, and suggest a possible protective effect of anti-E1E2 against disease progression.

Therapeutic control of hepatitis C virus: the role of neutralizing monoclonal antibodies.

Liver failure associated with hepatitis C virus (HCV) accounts for a substantial portion of liver transplantation. Although current therapy helps some patients with chronic HCV infection, adverse side effects and a high relapse rate are major problems. These problems are compounded in liver transplant recipients as reinfection occurs shortly after transplantation. One approach to control reinfection is the combined use of specific antivirals together with HCV-specific antibodies. Indeed, a number of human and mouse monoclonal antibodies to conformational and linear epitopes on HCV envelope proteins are potential candidates, since they have high virus neutralization potency and are directed to epitopes conserved across diverse HCV genotypes. However, a greater understanding of the factors contributing to virus escape and the role of lipoproteins in masking virion surface domains involved in virus entry will be required to help define those protective determinants most likely to give broad protection. An approach to immune escape is potentially caused by viral infection of immune cells leading to the induction hypermutation of the immunoglobulin gene in B cells. These effects may contribute to HCV persistence and B cell lymphoproliferative diseases.

Is telomere length in peripheral blood lymphocytes correlated with cancer susceptibility or radiosensitivity?

Mean terminal restriction fragment (TRF) lengths in white blood cells (WBCs) have been previously found to be associated with breast cancer. To assess whether this marker could be used as a test for breast cancer susceptibility in women, TRF length was measured in 72 treated female breast cancer patients and 1696 unaffected female controls between the ages of 45 and 77 from the Twin Research Unit at St Thomas' Hospital, as well as 140 newly diagnosed breast cancer cases and 108 mammographically screened unaffected controls from Guy's Hospital. Mean TRF was also tested for correlation with chromosome radiosensitivity and apoptotic response in the Guy's Hospital patients. After adjusting for age, smoking and body mass index, there was no significant difference in TRF lengths between the treated breast cancer patients and unaffected controls (P=0.71). A positive correlation between age-adjusted apoptotic response and mean TRF in newly diagnosed untreated breast cancer patients (P=0.008) was identified but no significant difference in TRF lengths between breast cancer patients and unaffected controls was detected (P=0.53). This suggests that TRF lengths in WBC, is not a marker of breast cancer susceptibility and does not vary significantly between affected women before and after treatment.

Atmospheric chemistry of the Z and E isomers of CF3CF=CHF; kinetics, mechanisms, and products of gas-phase reactions with Cl atoms, OH radicals, and O3.

Smog chamber/FTIR techniques were used to study the atmospheric chemistry of the Z and E isomers of CF3CF=CHF, which we refer to as CF3CF=CHF(Z) and CF3CF=CHF(E). The rate constants k(Cl + CF3CF=CHF(Z)) = (4.36 +/- 0.48) x 10-11, k(OH + CF3CF=CHF(Z)) = (1.22 +/- 0.14) x 10-12, and k(O3 + CF3CF=CHF(Z)) = (1.45 +/- 0.15) x 10-21 cm3 molecule-1 s-1 were determined for the Z isomer of CF3CF=CHF in 700 Torr air diluent at 296 +/- 2 K. The rate constants k(Cl + CF3CF=CHF(E)) = (5.00 +/- 0.56) x 10-11, k(OH + CF3CF=CHF(E)) = (2.15 +/- 0.23) x 10-12, and k(O3 + CF3CF=CHF(E)) = (1.98 +/- 0.15) x 10-20 cm3 molecule-1 s-1 were determined for the E isomer of CF3CF=CHF in 700 Torr air diluent at 296 +/- 2 K. Both the Cl-atom and OH-radical-initiated atmospheric oxidation of CF3CF=CHF give CF3C(O)F and HC(O)F in molar yields indistinguishable from 100% for both the Z and E isomer. CF3CF=CHF(Z) has an atmospheric lifetime of approximately 18 days and a global warming potential (100 year time horizon) of approximately 6. CF3CF=CHF(E) has an atmospheric lifetime of approximately 10 days and a global warming potential (100 year time horizon) of approximately 3. CF3CF=CHF has a negligible global warming potential and will not make any significant contribution to radiative forcing of climate change.

Microfabrication of screen-printed nanoliter vials with embedded surface-modified electrodes.

A self-contained ion-selective sensing system within a nanoliter-volume vial has been developed by integrating screen printing, laser ablation, and molecular imprinting techniques. Screen printing and laser ablation are used in tandem to fabricate nanoliter-volume vials with carbon and Ag/AgCl ring electrodes embedded in the sidewalls. Using multisweep cyclic voltammetry, the surface of the carbon electrode can be modified with a polypyrrole film. By polymerizing pyrrole in the presence of nitrate, pores complementary to the nitrate anion in size, shape, and charge distribution are formed in the resulting film. Electrochemical cells modified with this nitrate-imprinted polypyrrole film show a near-Nernstian response to nitrate, and excellent reproducibility. The integration of molecular recognition and electrochemical response in the nanoliter vials is demonstrated by the detection of as little as 0.36 ng nitrate in nanoliter-volume samples. The integration of tailored molecular recognition within nanoliter vials via established fabrication and imprinting protocols should result in a number of nanosensor devices with applications in BioMEMS and micro total analysis systems.

Timing of decompression and fixation after spinal cord injury--when is surgery optimal?

Spinal cord injury affects a large number of young individuals with a significant cost to affected persons, families and societies both in terms of economic and non-economic costs. To date, our interventions have been limited to prevention, good initial resuscitation, modest pharmacotherapy and nursing care. This review examines the role of surgery in spinal cord injury. The pathophysiology of spinal cord injury is reviewed. The compelling animal data for early decompression is discussed as well as evidence for improved neurological outcome with early decompression in humans. Finally, the impact of early surgery on non-neurological outcome and overall complication rates is examined with the concept of "damage control" discussed with relevance to spinal cord injury. It appears that favourable outcomes are achieved with early surgery, with reduced morbidity/mortality, but definitive data is still pending.

Comparative cohort study of the outcomes of deep lamellar keratoplasty and penetrating keratoplasty for keratoconus.

AIM: To compare the outcomes and complications of deep lamellar keratoplasty (DLK) and penetrating keratoplasty (PK) for keratoconus. METHODS: A cohort of 20 consecutive PKs, for keratoconus, was compared with 20 consecutive DLKs, for keratoconus. The PKs were performed between June 2000 and July 2001, the DLKs between October 2001 and October 2002. Surgery was performed by one surgeon. Best-corrected visual acuities (BCVA), refraction and complications were recorded at the time of surgery, 6 and 12 months postoperatively. chi(2)-tests were used to compare visual acuity outcomes and independent t-tests in the analysis of astigmatism. RESULTS: Groups were comparable for age, sex, and ethnicity. All PKs were uncomplicated. Two of the DLK group had microperforations of Descemet's membrane. There was no significant difference in the proportion of patients achieving 6/9 or better between the PK and DLK groups (85 vs 78%, P=0.54). PK patients were, however, more likely than the DLKs to achieve 6/6 at 1 year; 70% (14/20) of PKs compared to 22% of (4/18) DLKs (P=0.04). Astigmatism was significantly higher in the PKs compared to the DLKs (P=0.022). There were two cases of graft rejection in the PK group, while none in the DLKs. CONCLUSIONS: This study confirms good visual results from both PK and DLK in keratoconus with similarly high percentages reaching 6/9 BCVA. DLK appears to cause less astigmatism and also has the advantage of no endothelial graft rejection. The apparent cost, however, is a reduction in the likelihood of achieving 6/6 BCVA.