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Outbreak of food poisoning linked to leeks in cheese sauce: an unusual source.
No full textBetween 11-13 December 2018, local public health authorities in the West Midlands, England were alerted to 34 reports of diarrhoea with abdominal cramps. Symptom onset was ~10 h after diners ate Christmas meals at a restaurant between 7-9 December 2018. A retrospective case-control study, environmental and microbiological investigations were undertaken to determine the source and control the outbreak. An analytical study was undertaken with odds ratios (OR) and 95% confidence intervals (CI). Forty persons were recruited to the analytical study (28/40 cases). Multivariable analysis found that leeks in cheese sauce was the only item associated with illness (aOR 51.1; 95% CI 4.13-2492.1). Environmental investigations identified significant lapses in food safety, including lapses in temperature control during cooking and hot holding, likely cross-contamination between raw and cooked foods and the reuse of leftover cheese sauce for the next day's service. No food samples were taken during the exposure period. Two faecal samples were positive for Clostridium perfringens with one confirming the enterotoxigenic gene. Cheese sauce is an unusual vehicle for the organism and the first time this has been reported in England
Synthesis and characterisation of isothiocyanate functionalised silicon nanoparticles and their uptake in cultured colonic cells.
No full textThe functionalisation of silicon nanoparticles with a terminal thiocyanate group, producing isothiocyanate-capped silicon nanoparticles (ITC-capped SiNPs) has been successfully attained. The procedure for the synthesis is a two-step process that occurs via thermally induced hydrosilylation of hydrogen terminated silicon nanoparticles (H-SiNPs) and further reaction with potassium thiocyanate (KSCN). The synthesis was confirmed by Fourier transform infrared (FTIR) spectroscopy and X-Ray photoelectron spectroscopy (XPS). At the same time, the internalisation and the cytotoxicity of the ITC-capped SiNPs in vitro were assessed in two cell lines: Caco-2, human colorectal cancer cells and CCD-841, human colon "normal" cells. The results showed that above concentrations of 15 µg ml-1, the cell viability of both cell lines was depleted significantly when treated with ITC SiNPs, particularly over a 48 hour period, to approximately 20% cell viability at the highest treatment concentration (70 µg ml-1). Flow cytometry was employed to determine cellular uptake in Caco-2 cells treated with ITC SiNPs. It was observed that at lower SiNP concentrations, uptake efficiency was significantly improved for time periods under 12 hours; overall it was noted that cellular uptake was positively dependent on the period of incubation and the temperature of incubation. As such, it was concluded that the mechanism of uptake of ITC SiNPs was through endocytosis. Synchrotron FTIR spectroscopy, by means of line spectral analysis and IR imaging, provided further evidence to suggest the internalisation of ITC SiNPs displays a strong localisation, with an affinity for the nucleus of treated Caco-2 cells
Acute kidney injury calculated using admission serum creatinine underestimates 30-day and 1-year mortality after acute stroke.
No full textBackground
Acute kidney injury (AKI) diagnosis requires ascertainment of change from a known baseline. Although pre-admission serum creatinine (SCr) is recommended, to date, all studies of AKI in acute stroke have used the first SCr on admission.
Methods
All patients admitted with an acute stroke to an emergency hospital were recruited. We compared use of pre-admission SCr with admission SCr to diagnose AKI. Regression analyses were used to identify risk factors for 30-day and 1-year mortality, respectively.
Results
A total of 1354 patients were recruited from December 2012 to September 2015. Incidence of AKI was 18.7 and 19.9% using pre-admission SCr and admission SCr, respectively. Diagnosis of AKI was associated with significantly increased 30-day and 1-year mortality. Diagnosis of AKI using pre-admission SCr had a stronger relationship with both 30-day and 1-year mortality. In 443 patients with a pre-admission SCr and at least two SCr during admission, AKI diagnosed using pre-admission SCr had a stronger relationship than AKI diagnosed using admission SCr with 30-day mortality [odds ratio (OR) = 2.64; 95% confidence interval (CI) 1.36-5.12; P = 0.004 versus OR = 2.10; 95% CI 1.09-4.03; P = 0.026] and 1-year mortality [hazard ratio (HR) = 1.90, 95% CI 1.32-2.76; P = 0.001 versus HR = 1.47; 95% CI 1.01-2.15; P = 0.046] in fully adjusted models.
Conclusions
AKI after stroke is common and is associated with increased 30-day and 1-year mortality. Using first SCr on admission gives a comparable AKI incidence to pre-admission SCr, but underestimates 30-day and 1-year mortality risk
Nonadherence to antihypertensive medications is related to pill burden in apparent treatment-resistant hypertensive individuals.
No full textOBJECTIVE
Nonadherence to medication is present in at least 50% of patients with apparent treatment-resistant hypertension. We examined the factors associated with nonadherence as detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based urine antihypertensive drug assay.
METHODS
All urine antihypertensive test results, carried out for uncontrolled hypertension (BP persistently >140/90 mmHg) between January 2015 and December 2016 at a single toxicology laboratory were analysed. Drugs detected were compared with the antihypertensive drugs prescribed. Patients were classified as adherent (all drugs detected), partially nonadherent (at least one prescribed drug detected) or completely nonadherent (no drugs detected). Demographic and clinical parameters were compared between the adherent and nonadherent groups. Binary logistic regression analysis was performed to determine association between nonadherence and demographic and clinical factors.
RESULTS
Data on 300 patients from nine hypertension centres across the United Kingdom were analysed. The median age was 59 years, 47% women, 71% Caucasian, median clinic BP was 176/95 mmHg and the median number of antihypertensive drugs prescribed was four. One hundred and sixty-six (55%) were nonadherent to prescribed medication with 20% of these being completely nonadherent. Nonadherence to antihypertensive medication was independently associated with younger age, female sex, number of antihypertensive drugs prescribed, total number of all medications prescribed (total pill burden) and prescription of a calcium channel blocker.
CONCLUSION
This LC-MS/MS urine analysis-based study suggests the majority of patients with apparent treatment-resistant hypertension are nonadherent to prescribed treatment. Factors that are associated with nonadherence, particularly pill burden, should be taken into account while treating these patients
Risk of bias assessment of test comparisons was uncommon in comparative accuracy systematic reviews: an overview of reviews.
No full textOBJECTIVES
Comparative diagnostic test accuracy systematic reviews (DTA reviews) assess the accuracy of two or more tests and compare their diagnostic performance. We investigated how comparative DTA reviews assessed the risk of bias (RoB) in primary studies that compared multiple index tests.
STUDY DESIGN AND SETTING
This is an overview of comparative DTA reviews indexed in MEDLINE from January 1st to December 31st, 2017. Two assessors independently identified DTA reviews including at least two index tests and containing at least one statement in which the accuracy of the index tests was compared. Two assessors independently extracted data on the methods used to assess RoB in studies that directly compared the accuracy of multiple index tests.
RESULTS
We included 238 comparative DTA reviews. Only two reviews (0.8%, 95% confidence interval 0.1 to 3.0%) conducted RoB assessment of test comparisons undertaken in primary studies; neither used an RoB tool specifically designed to assess bias in test comparisons.
CONCLUSION
Assessment of RoB in test comparisons undertaken in primary studies was uncommon in comparative DTA reviews, possibly due to lack of existing guidance on and awareness of potential sources of bias. Based on our findings, guidance on how to assess and incorporate RoB in comparative DTA reviews is needed
Cellular therapies for the treatment of immune-mediated GI and liver disease.
No full textINTRODUCTION
Immune-mediated liver and gastrointestinal diseases are chronic conditions that lack curative treatments. Despite advances in the understanding and treatment of these conditions, they frequently remain refractory to treatment and represent a significant unmet need. Cellular therapies are an emerging option and hold the potential to have a major impact.
DATA SOURCES
A literature review was carried out using Pubmed. Keywords used for search were 'ATMP', 'immune mediated', 'autoimmune liver disease' and 'immune mediated gastrointestinal conditions', 'cell therapy', 'MSC', 'HSCT', 'Regulatory T cells', 'GVHD', 'Coeliac disease' 'IBD', 'PSC', 'AIH', 'PBC'. No new data were generated or analysed in support of this review.
AREAS OF AGREEMENT
There is substantial evidence from clinical trials to support the use of cell therapies as a treatment for immune-mediated liver and gastrointestinal conditions. Cellular therapy products have the ability to 'reset' the dysregulated immune system and this in turn can offer a longer term remission. There are ongoing clinical trials with mesenchymal stromal cells (MSCs) and other cells to evidence their efficacy profile and fill the gaps in current knowledge. Insights gained will inform future trial designs and subsequent therapeutic applications.
AREAS OF CONTROVERSY
There remains some uncertainty around the extrapolation of results from animal studies to clinical trials. Longevity of the therapeutic effects seen after the use of cell therapy needs to be scrutinized further. Heterogeneity in the selection of cells, source, methods of productions and cell administration pose challenges to the interpretation of the data.
GROWING POINTS
MSCs are emerging as a key therapeutic cells in immune-mediated liver and gastrointestinal conditions. Ongoing trials with these cells will provide new insights and a better understanding thus informing future larger scale studies.
AREAS TIMELY FOR DEVELOPING RESEARCH
Larger scale clinical trials to build on the evidence from small studies regarding safety and efficacy of cellular therapy are still needed before cellular therapies can become off the shelf treatments. Alignment of academia and industry to standardize the processes involved in cell selection, manipulation and expansion and subsequent use in clinical trials is an important avenue to explore further
Xanthogranulomatous epithelial tumor: report of 6 cases of a novel, potentially deceptive lesion with a predilection for young women.
No full textEpithelial marker expression and/or epithelial differentiation, as well as "anomalous" expression of keratins, are features of some soft tissue tumors. Recently, we have encountered an unusual mesenchymal tumor composed of bland, distinctly eosinophilic, keratin-positive epithelial cells, which were almost entirely obscured by xanthogranulomatous inflammation. Six cases were identified (5 F, 1 M; 16-62 years (median 21 years)) arising in soft tissue (n = 4) and bone (n = 2) and ranging in size from 2 to 7 cm. The tumors were generally circumscribed, with a fibrous capsule containing lymphoid aggregates, and consisted in large part of a sheet-like proliferation of foamy histiocytes, Touton-type and osteoclast-type giant cells, and chronic inflammatory cells. Closer inspection, however, disclosed a distinct population of uniform, cytologically bland mononuclear cells with brightly eosinophilic cytoplasm arranged singly and in small nests and cords. Overt squamous and/or glandular differentiation was absent. By immunohistochemistry, these cells were diffusely positive with the OSCAR and AE1/AE3 keratin antibodies, and focally positive for high-molecular weight keratins; endothelial and myoid markers were negative and SMARCB1 was retained. RNA-seq identified a PLEKHM1 variant of undetermined significance in one case, likely related to this patient's underlying osteopetrosis. Follow-up to date has been benign. In summary, we have identified a novel tumor of soft tissue and bone with a predilection for young females, provisionally termed "xanthogranulomatous epithelial tumor". These unusual lesions do not appear to arise from adnexa, or represent known keratin-positive soft tissue tumors, and the origin of their constituent epithelial cells is obscure. The natural history of this distinctive lesion appears indolent, although study of additional cases and longer term follow-up are needed
Radiosensitising Cancer Using Phosphatidylinositol-3-Kinase (PI3K), Protein Kinase B (AKT) or Mammalian Target of Rapamycin (mTOR) Inhibitors.
No full textRadiotherapy is routinely used as a neoadjuvant, adjuvant or palliative treatment in various cancers. There is significant variation in clinical response to radiotherapy with or without traditional chemotherapy. Patients with a good response to radiotherapy demonstrate better clinical outcomes universally across different cancers. The PI3K/AKT/mTOR pathway upregulation has been linked to radiotherapy resistance. We reviewed the current literature exploring the role of inhibiting targets along this pathway, in enhancing radiotherapy response. We identified several studies using in vitro cancer cell lines, in vivo tumour xenografts and a few Phase I/II clinical trials. Most of the current evidence in this area comes from glioblastoma multiforme, non-small cell lung cancer, head and neck cancer, colorectal cancer, and prostate cancer. The biological basis for radiosensitivity following pathway inhibition was through inhibited DNA double strand break repair, inhibited cell proliferation, enhanced apoptosis and autophagy as well as tumour microenvironment changes. Dual PI3K/mTOR inhibition consistently demonstrated radiosensitisation of all types of cancer cells. Single pathway component inhibitors and other inhibitor combinations yielded variable outcomes especially within early clinical trials. There is ample evidence from preclinical studies to suggest that direct pharmacological inhibition of the PI3K/AKT/mTOR pathway components can radiosensitise different types of cancer cells. We recommend that future in vitro and in vivo research in this field should focus on dual PI3K/mTOR inhibitors. Early clinical trials are needed to assess the feasibility and efficacy of these dual inhibitors in combination with radiotherapy in brain, lung, head and neck, breast, prostate and rectal cancer patients
Echocardiographic Findings in Covid-19 Pneumonia.
No full textThe aim of this study was to characterize the echocardiographic phenotype of patients with Covid-19 pneumonia and its relation to biomarkers. Seventy-four patients (59±13 years, 78% male) admitted with Covid-19 were included after referral for transthoracic echocardiography (TTE) as part of routine care. A level 1 British Society of Echocardiography TTE assessed chamber size and function, valvular disease and likelihood of pulmonary hypertension. The chief abnormalities were right ventricular (RV) dilatation (41%) and RV dysfunction (27%). RV impairment was associated with increased D-dimer and CRP levels. In contrast, left ventricular (LV) function was hyper-dynamic or normal in most (89%) patients
Infection in older adults: a qualitative study of patient experience.
No full textBACKGROUND
Infection is common in older adults. Serious infection has a high mortality rate and is associated with unplanned hospital admissions. Little is known about the factors that prompt older patients to seek medical advice when they may have an infection.
AIM
To explore the symptoms of infection from the perspective of older adults, and when and why older patients seek healthcare advice for a possible infection.
DESIGN AND SETTING
A qualitative interview study among adults aged ≥70 years with a clinical diagnosis of infection recruited from ambulatory care units in Oxford, UK.
METHOD
Interviews were semi-structured and based on a flexible topic guide. Participants were given the option to be interviewed with their carer. Thematic analysis was facilitated using NVivo (version 11).
RESULTS
A total of 28 participants (22 patients and six carers) took part. Patients (aged 70-92 years) had experienced a range of different infections. Several early non-specific symptoms were described (fever, feeling unwell, lethargy, vomiting, pain, and confusion/delirium). Internally minimising symptoms was common and participants with historical experience of infection tended to be better able to interpret their symptoms. Factors influencing seeking healthcare advice included prompts from family, specific or intolerable symptoms, symptom duration, and being unable to manage with self-care. For some, not wanting to be a burden affected their desire to seek help.
CONCLUSION
Tailored advice to older adults highlighting early symptoms of infection may be beneficial. Knowing whether patients have had previous experience of infection may help healthcare professionals in assessing older patients with possible infection