Edel M. Quinn

MicroRNA-146a Is Upregulated by and Negatively Regulates TLR2 Signaling

TLR signaling is a crucial component of the innate immune response to infection. MicroRNAs (miRNAs) have been shown to be upregulated during TLR signaling. Specifically, microRNA-146a (miR-146a) plays a key role in endotoxin tolerance by downregulating interleukin-1 receptor-associated kinase 1 (IRAK-1). The aim of this study was to assess the role of miR-146a in the TLR2 signaling and development of bacterial lipoprotein (BLP) self-tolerance and cross-tolerance to bacteria. Expression of miR-146a increased in a dose- and time-dependent manner in BLP-stimulated human THP-1 promonocytic cells. In BLP-tolerised cells miR-146a was even further upregulated in response to BLP re-stimulation (p<0.001). Re-stimulation of BLP-tolerised cells with heat-killed gram-negative Salmonella typhimurium (S. typhimurium), but not gram-positive Staphylococcus aureus (S. aureus), led to significant overexpression of miR-146a (p<0.05). Transfection of naive cells with a miR-146a mimic substantially suppressed TNF-α production (p<0.05). Furthermore, overexpression of miR-146a resulted in strong reduction in IRAK-1 and phosphorylated IκBα expression in naive and S. typhimurium-stimulated THP-1 cells. Collectively, miR-146a is upregulated in response to BLP and bacterial stimulation in both naive and BLP-tolerised cells. Overexpression of miR-146a induces a state analogous to tolerance in BLP-stimulated cells and therefore may represent a future target for exogenous modulation of tolerance during microbial infection and sepsis.

The emerging role of microRNA in regulation of endotoxin tolerance

Endotoxin tolerance is a phenomenon where cells show reduced responsiveness toward repeated endotoxin stimulation. Regulation of tolerance occurs at multiple levels of the cell signaling cascade, and many of these levels are potentially regulated by miRNA, which are a class of small RNA that bind to mRNA to down‐regulate gene expression at the post‐transcriptional level. Roles have been identified for miR‐146a, miR‐221, miR‐579, miR‐125b, miR‐155, let‐7e, and miR‐98 in regulating the TLR4 signaling pathway during the development of endotoxin tolerance at receptor, signaling pathway, and gene transcription and translational levels. miRNA represent exciting, new potential targets in attempts to exogenously modulate development of endotoxin tolerance.

Who's talking about breast cancer? Analysis of daily breast cancer posts on the internet

OBJECTIVE Breast cancer is the cancer most commonly searched for on the internet. Our aim was to assess daily new breast cancer related posting on the internet. METHODS We analyzed numbers of new daily posts for common cancers for one month and subsequently analyzed content of 1426 breast cancer related posts. We also assessed use of online discussion forums for breast cancer related dialogue. RESULTS Breast related topics had significantly more posts per day compared to others (mean 66.7, p < 0.01). Most posts were on media sites (65.8%). Accuracy levels were high (87.5%) but significantly lower where posted on blogs and discussion forums (p < 0.001). Anonymous posts were common (55%) and less likely to be accurate (p < 0.001). Use of discussion forums has exponentially increased over the last five years (p < 0.001). CONCLUSIONS The internet has become a primary forum within which health information, particularly relating to breast cancer, is both sought and shared. Increasingly information is provided by patients themselves.

B7-H3 Participates in the Development of Experimental Pneumococcal Meningitis by Augmentation of the Inflammatory Response via a TLR2-Dependent Mechanism

In addition to a well-documented role in regulating T cell-mediated immune responses, B7-H3, a newly discovered member of the B7 superfamily, has been recently identified as a costimulator in the innate immunity-mediated inflammatory response. In this study, we further report that B7-H3 participates in the development of pneumococcal meningitis in a murine model. Exogenous administration of B7-H3 strongly amplified the inflammatory response, exacerbated blood–brain barrier disruption, and aggravated the clinical disease status in Streptococcus pneumoniae-infected C3H/HeN wild-type mice. Consistent with the in vivo findings, B7-H3 substantially augmented proinflammatory cytokine and chemokine production, upregulated NF-κB p65 and MAPK p38 phosphorylation, and enhanced the nuclear transactivation of NF-κB p65 at both TNF-α and IL-6 promoters in S. pneumoniae-stimulated primary murine microglia cells. These B7-H3–associated in vitro and in vivo effects appeared to be dependent on TLR2 signaling, as B7-H3 almost completely lost its amplifying actions in both TLR2-deficient microglial cells and TLR2-deficient mice. Furthermore, administration of the anti–B7-H3 mAb (MIH35) attenuated the inflammatory response and ameliorated blood–brain barrier disruption in S. pneumoniae-infected wild-type mice. Collectively, our results indicate that B7-H3 plays a contributory role in the development of S. pneumoniae infection-induced bacterial meningitis.

Temporal artery biopsy is not required in all cases of suspected giant cell arteritis.

BACKGROUND Temporal artery biopsy (TAB) is performed during the diagnostic workup for giant cell arteritis (GCA), a vasculitis with the potential to cause irreversible blindness or stroke. However, treatment is often started on clinical grounds, and TAB result frequently does not influence patient management. The aim of this study was to assess the need for TAB in cases of suspected GCA. METHODS We performed a retrospective review of 185 TABs performed in our institution from 1990 to 2010. Patients were identified through the Hospital In-Patient Enquiry database and theater records. Clinical findings, erythrocyte sedimentation rate, steroid treatment preoperatively, American College of Rheumatology (ACR) criteria for GCA score, biopsy result, and follow-up were recorded. RESULTS Fifty-eight (31.4%) biopsies were positive for GCA. Presence of jaw claudication (P = 0.001), abnormal fundoscopy (P = 0.001), and raised erythrocyte sedimentation rate (P = 0.001) were significantly associated with GCA. The strongest association with positive biopsy was seen with the prebiopsy ACR score (P < 0.001). Twenty-four (13.7%) patients had undergone biopsy, despite no potential for meeting ACR criteria preoperatively. None of these were positive. Overall, 29 (16.4%) patients had management altered by TAB result. CONCLUSIONS Our results confirm that TAB does not affect management in the majority of patients with suspected GCA. We conclude that TAB has benefit only for patients who score 2 or 3 on the ACR criteria for GCA without biopsy.

The impact of routine open nonsuction drainage on fluid accumulation after thyroid surgery: a prospective randomised clinical trial

BackgroundThyroid drains following thyroid surgery are routinely used despite minimal supportive evidence. Our aim in this study is to determine the impact of routine open drainage of the thyroid bed postoperatively on ultrasound-determined fluid accumulation at 24 hours.MethodsWe conducted a prospective randomised clinical trial on patients undergoing thyroid surgery. Patients were randomly assigned to a drain group (n = 49) or a no-drain group (n = 44) immediately prior to wound closure. Patients underwent a neck ultrasound on day 1 and day 2 postoperatively. After surgery, we evaluated visual analogue scale pain scores, postoperative analgesic requirements, self-reported scar satisfaction at 6 weeks and complications.ResultsThere was significantly less mean fluid accumulated in the drain group on both day 1, 16.4 versus 25.1 ml (P-value = 0.005), and day 2, 18.4 versus 25.7 ml (P-value = 0.026), following surgery. We found no significant differences between the groups with regard to length of stay, scar satisfaction, visual analogue scale pain score and analgesic requirements. There were four versus one wound infections in the drain versus no-drain groups. This finding was not statistically significant (P = 0.154). No life-threatening bleeds occurred in either group.ConclusionsFluid accumulation after thyroid surgery was significantly lessened by drainage. However, this study did not show any clinical benefit associated with this finding in the nonemergent setting. Drains themselves showed a trend indicating that they may augment infection rates. The results of this study suggest that the frequency of acute life-threatening bleeds remains extremely low following abandoning drains. We advocate abandoning routine use of thyroid drains.Trial registrationISRCTN94715414

Clinical unity and community empowerment: the use of smartphone technology to empower community management of chronic venous ulcers through the support of a tertiary unit

Background Chronic ulcers affect roughly 60,000 Irish people, at a total cost of €600,000,000, or €10,000 per patient annually. By virtue of their chronicity, these ulcers also contribute a significant burden to tertiary outpatient vascular clinics. Objective We propose utilizing mobile phone technology to decentralise care from tertiary centres to the community, improving efficiency and patient satisfaction, while maintaining patient safety. Methods Bespoke mobile software was developed for Apples iPhone 4 platform. This allowed for the remote collection of patient images prospectively and their transmission with clinical queries, from the primary healthcare team to the tertiary centre. Training and iPhones were provided to five public health nurses in geographically remote areas of the region. Data were uploaded securely and user end software was developed allowing the review and manipulation of images, along with two way communication between the teams. Establishing reliability, patients were reviewed clinically as well as remotely, and concordance analysed. Qualitative data were collected through focus group discussion. Results From October to December 2011 eight patients (61–83 yrs, mean 75.3 yrs) with chronic venous ulceration and their five public health nurses were recruited. Data were transmitted using 3 G, Edge, GPRS and WiFi, at a mean speed of 69.03 kps. Concordance was 100% for wound bed assessment, 80% for skin integrity/colour and 60% for exudate assessment. Focus group analysis explored the concept, practicalities and future applications of the system. Conclusions With an evolving national data network, the secure transmission of clinical images is a safe alternative to regular clinic appointments for patients with chronic venous ulceration. With further development, and packaged as a freely downloadable application, this has the potential to support the community care of chronic wounds.

Routine calcium measurement is not necessary after most thyroid surgeries: a prospective clinical study

Clin. Otolaryngol. 2010, 35, 468–473

Information Needs of Patients With Breast Cancer at Years One, Three, and Five After Diagnosis

Introduction: The information needs of breast cancer patients at diagnosis have been studied extensively. However, with cancer survival improving, the era of cancer care has entered a more chronic phase with an associated paucity of data related to longer term information requirements. The aim of the present study was to assess and compare the information needs of breast cancer patients during the first 5 years after the diagnosis. Patients and Methods: A total of 105 follow‐up consecutive patients presenting to a tertiary referral breast cancer center from August to October 2017 were recruited. The patients were divided into groups by the years after the diagnosis (1, 3, and 5 years). Each patient completed the Toronto Information Needs Questionnaire for Breast Cancer. Results: The number of patients in each group was as follows: 23 at 1 year, 38 at 3 years, and 44 at 5 years after the initial diagnosis. The median Toronto Information Needs Questionnaire for Breast Cancer score was 4.15 on a 5‐point Likert scale of breast cancer information needs (1, not important to 5, extremely important). No difference was found in the median scores at 1, 3, and 5 years. Information pertaining to the disease process was rated as most important (median, 4.50), and information regarding the psychosocial aspect of disease was ranked lowest (median, 3.75). Conclusion: The information needs of patients with breast cancer remain high throughout the follow‐up period after the diagnosis. In an era of prolonged survival, attention to the information needs of patients at follow‐up examinations is as important as at the time of diagnosis and treatment.