Systematic review of prognostic importance of extramural venous invasion in rectal cancer

AIM: To systematically review the survival outcomes relating to extramural venous invasion in rectal cancer. METHODS: A systematic review was conducted using PRISMA guidelines. An electronic search was carried out using MEDLINE, EMBASE, CINAHL, Cochrane library databases, Google scholar and Pubmed until October 2014. Search terms were used in combination to yield articles on extramural venous invasion in rectal cancer. Outcome measures included prevalence and 5-year survival rates. These were graphically displayed using Forest plots. Statistical analysis of the data was carried out. RESULTS: Fourteen studies reported the prevalence of extramural venous invasion (EMVI) positive patients. Prevalence ranged from 9%-61%. The pooled prevalence of EMVI positivity was 26% [Random effects: Event rate 0.26 (0.18, 0.36)]. Most studies showed that EMVI related to worse oncological outcomes. The pooled overall survival was 39.5% [Random effects: Event rate 0.395 (0.29, 0.51)]. CONCLUSION: Historically, there has been huge variation in the prevalence of EMVI through inconsistent reporting. However the presence of EMVI clearly leads to worse survival outcomes. As detection rates become more consistent, EMVI may be considered as part of risk-stratification in rectal cancer. Standardised histopathological definitions and the use of magnetic resonance imaging to identify EMVI will improve detection rates in the future

Bacterial isolates from neutropenic febrile pediatric patients and their sensitivity patterns to antibiotics

Patients on cytotoxic therapy often develop neutropenia and fever. Our interest was to identify the common pathogens isolated from such patients and to study the sensitivity patterns of these organisms to the antibiotics used in their treatment. Thus, guidelines can be established by hospitals to identify which antibiotics can be used in the treatment of these patients when the results of cultures and sensitivities are not available. We conducted a retrospective study of neutropenic pediatrics presenting to AKUH from July, 1990 to June, 1996. A total of 153 isolates in 35 different patients were studied. Samples for culture were taken from the sites at risk. The majority of samples consisted of blood, stool, pus and urine. Twenty stool samples were also sent for microscopy. Malignancies were both hematological and non-hematological. Gram negatives were isolated in 52.9%, gram positives in 33.9% and parasites in 13.2%. Salmonella paratyphi B was the most commonly isolated organism, followed by Pseudomonas aeroginosa, Giardia lamblia was the most common parasite. Sensitivity patterns of these organisms to antibiotics studied showed that Escheria coli had the lowest sensitivity rate being only 40% sensitive to Aztreonam and 64% sensitive to Ofloxacillin. A comparison was made between our findings and those reported in literature, as well as the risk factors for developing neutropenia. A guide to management is also discussed

Enhanced recruitment of genetically modified CX3CR1-positive human T cells into Fractalkine/CX3CL1 expressing tumors: importance of the chemokine gradient.

BACKGROUND: Adoptive T-cell based immunotherapies constitute a promising approach to treat cancer, however, a major problem is to obtain effective and long-lasting anti-tumor responses. Lack of response may be due to insufficient trafficking of specific T cells to tumors. A key requirement for efficient migration of cytotoxic T cells is that they express chemokine receptors that match the chemokines produced by tumor or tumor-associated cells. METHODS: In this study, we investigated whether the in vivo tumor trafficking of activated T cells could be enhanced by the expression of the chemokine receptor CX3CR1. Two human colorectal cancer cell lines were used to set up a xenograft tumor model in immunodeficient mice; the NCI-H630, constitutively expressing the chemokine ligand CX3CL1 (Fractalkine), and the RKO cell line, transduced to express CX3CL1. RESULTS: Human primary T cells were transduced with the receptor CX3CR1-eGFP. Upon in vivo adoptive transfer of genetically modified CX3CR1-T cells in mice bearing NCI-H630 tumors, enhanced lymphocyte migration and tumor trafficking were observed, compared to mice receiving Mock-T cells, indicating improved homing ability towards ligand-expressing tumor cells. Furthermore, significant inhibition of tumor growth was found in mice receiving modified CX3CR1-T cells. In contrast, tumors formed by RKO cells transduced with the ligand (RKO-CX3CL1) were not affected, nor more infiltrated upon transfer of CX3CR1-T lymphocytes, likely because high levels of the chemokine were shed by tumor cells in the systemic circulation, thus nullifying the blood-tissue chemokine gradient. CONCLUSIONS: This study demonstrates that ectopic expression of CX3CR1 enhanced the homing of adoptively transferred T cells towards CX3CL1-producing tumors, resulting in increased T cell infiltration in tumor tissues and decreased tumor growth. Our results also establish that a correct chemokine gradient between the systemic circulation and the tumor is an essential requirement in adoptive T-cell based immunotherapy to efficiently recruit T cell effectors at the correct sites

COVID-19: Causes of anxiety and wellbeing support needs of healthcare professionals in the UK: A cross-sectional survey.

BACKGROUND: COVID-19 has caused acute changes in healthcare delivery; this may impact mental health and wellbeing needs of healthcare professionals (HCPs). AIMS: We aimed to identify the causes of anxiety in HCPs during the COVID-19 pandemic, to assess whether HCPs felt they had adequate mental health and wellbeing support and to identify their unmet support needs. METHOD: We used a web-based survey utilising an online tool circulated to UK HCPs over 5 weeks. Self-perceived anxiety levels prior to and during the COVID-19 pandemic were measured on a 10-point Likert-type rating scale. RESULTS: The survey was completed by 558 HCPs. During the pandemic, self-perceived anxiety scores significantly increased from a median of 2 to 7 (paired Wilcoxon signed-rank test; p<0.001). The main reasons were concerns about exposure to SARS-CoV-2 and lack of personal protective equipment. Other wide-ranging reasons were identified. Only 41% of respondents felt there was adequate support. Thematic analysis of what support HCPs wanted identified 13 wide-ranging themes; including effective leadership and peer support. CONCLUSION: Anxiety levels in HCPs significantly increased during the COVID-19 pandemic and the main causes were identified. Many HCPs felt there was inadequate support and identified what support they needed. Implementing effective strategies to support HCPs' unmet wellbeing needs are required as a matter of urgency

Tomato yellow leaf curl virus (TYLCV) alters the phytochemical constituents in tomato fruits.

An investigation was conducted in order to evaluate the responses of field grown tomato varieties (Marglove and Roma VF) to tomato yellow leaf curl virus (TYLCV). Fruit samples from the virus-infected and uninfected plants were collected at 20 (early stage), 40 (intermediate stage) and 60 days (ripening stage) after anthesis. Results showed higher virus RNA content in fruits of infected plants at early (42.48 to 38.24%) and intermediate stages (34.35 to 19.57%). There was a substantial decrease in DNA content (27.27 and 21.05%) at early and (23.08 and 43.75%) at intermediate stages of both Marglove and Roma VF, compared to the control, respectively. Similarly, indole acetic acid content was also decreased (27.08 and 24.29%) in fruits of virus-infected Marglove and Roma VF, respectively. The free ascorbic acid content was found lower (35.29 to 51.52%), while combined ascorbic acid was higher (13.91 to 33.33%) in both varieties. Neither the responses of individual organic acids nor their concentrations in fruits of infected and control plants were identical. Fumaric acid was not detected either in fruits of infected plants of Marglove or in healthy and infected Roma VF. Individual fruit weight and fruit numbers per plant were lower in the virus-infected plants. This study indicates that the yield of infected tomato plants could be reduced by the infection of TYLCV due to the changes in the concentrations of phytochemical constituents. This suggests that monitoring and management of TYLCV incidence is crucial for yield and quality optimization of field grown tomato

Improving waiting times for abscess surgery: Experience from a complete audit cycle

Friday, 28th July 1916

Increased levels of multiple forms of dihydrofolate reductase in peripheral blood leucocytes of cancer patients receiving haematopoietic colony-stimulating factors: Interim analysis

The precise mechanism whereby granulocytes proliferate when haematopoietic colony stimulating factors (CSFs) are used in neutropenic cancer patients is poorly understood. The purpose of this study was to investigate whether these cytokines bring about leucocyte proliferation by increasing the levels of multiple forms of dihydrofolate reductase (DHFR). Blood samples were collected from 36 cancer patients (25 males and 11 females) with chemotherapy-induced neutropenia. One sample of blood from each patient was obtained before therapy either with CSF, such as granulocyte colony stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) or with placebo, and another one at the time of resolution of neutropenia. Peripheral blood leucocytes in these blood samples were counted, separated and lysed. From lysates, cytoplasmic samples were prepared and analyzed for active DHFR by a methotrexate-binding assay and for total immunoreactive DHFR by an enzyme linked immunosorbent assay. The increase in total leucocyte count (TLC) was most prominent (P \u3c 0.005) in the CSF group and less so (P \u3c 0.05) in the placebo group. The mean +/- SD concentration values of active DHFR before and after stimulation with GM-CSF found were to be 0.34 +/- 0.4 ng/mg protein and 0.99 +/- 0.82 ng/mg protein, respectively, and in the group treated with G-CSF, 0.24 +/- 0.32 ng/mg protein and 1.18 +/- 2.4 ng/mg protein, respectively. This increase in active DHFR after stimulation with CSF was statistically significant (P \u3c 0.05). Similarly, concentration values of immunoreactive but nonfunctional form of DHFR (IRE) were 110 +/- 97 ng/mg protein and 605 +/- 475 ng/mg protein before and after stimulation with GM-CSF, and 115 +/- 165 ng/mg protein and 1,054 +/- 1,095 ng/ mg protein before and after stimulation with G-CSF. This increase in concentration of IRE after stimulation with GM-CSF or G-CSF was statistically significant (P \u3c 0.005). In the control group, there was an increase in the concentration of both active DHFR and IRE after treatment with placebo. However, this was not statistically significant. Resolution of neutropenia was quicker in the groups treated with CSF compared to the control group. Results of this study indicate that colony stimulating factors (G-CSF and GM-CSF) induce white cell proliferation by increasing the levels of multiple forms of DHFR

A temperature dependent virus binding assay reveals the presence of neutralising antibodies in human cytomegalovirus gB vaccine recipients’ sera

Human cytomegalovirus (HCMV) remains an important cause of mortality in immune-compromised transplant patients and following congenital infection. Such is the burden, an effective vaccine strategy is considered to be of the highest priority. The most successful vaccines to date have focused on generating immune responses against glycoprotein B (gB) – a protein essential for HCMV fusion and entry. We have previously reported that an important component of the humoral immune response elicited by gB/MF59 vaccination of patients awaiting transplant is the induction of non-neutralizing antibodies that target cell-associated virus with little evidence of concomitant classical neutralizing antibodies. Here we report that a modified neutralization assay that promotes prolonged binding of HCMV to the cell surface reveals the presence of neutralizing antibodies in sera taken from gB-vaccinated patients that cannot be detected using standard assays. We go on to show that this is not a general feature of gB-neutralizing antibodies, suggesting that specific antibody responses induced by vaccination could be important. Although we can find no evidence that these neutralizing antibody responses are a correlate of protection in vivo in transplant recipients their identification demonstrates the utility of the approach in identifying these responses. We hypothesize that further characterization has the potential to aid the identification of functions within gB that are important during the entry process and could potentially improve future vaccine strategies directed against gB if they prove to be effective against HCMV at higher concentrations