An outbreak of Shigella boydii serotype 20 in January 2015 amongst United Kingdom healthcare workers involved in the Ebola response in Sierra Leone.

In January 2015, Public Health England and the United Kingdom (UK) Ministry of Defence investigated cases of diarrhoea and fever in military personnel recently returned to the UK after supporting the response to the Ebola epidemic in Sierra Leone. Tests for Ebola virus infection were negative. PCR tests detected the ipaH gene in 10/12 faecal specimens, and Shigella boydii serotype 20 was isolated from 7 patients. A case control study was undertaken and analysed using multivariable logistic regression. Consumption of a coronation chicken lunch at the transit camp in Sierra Leone (SL) 24-48 h prior to departure for the UK was significantly associated with disease [adjusted odds ratio (OR) 28.15, 95 % CI: 1.87-422.65]. In the context of heightened concern during the Ebola epidemic, this outbreak highlights the importance of rapid and effective microbiological and epidemiological investigations to identify the aetiological agent in patients presenting with fever and diarrhoea.

Malaria Chemoprophylaxis and Self-Reported Impact on Ability to Work: Mefloquine Versus Doxycycline.

BACKGROUND: It is well known that both mefloquine and doxycycline are commonly associated with adverse effects when taken for malaria chemoprophylaxis. However, the relative impact of these on travelers' ability to work is not so well understood. The aim of this study was to identify which drug has a lesser impact on the ability to work as measured by self-reported severity of adverse effects via a questionnaire. METHODS: This was a questionnaire-based two-arm cohort study. Participants were soldiers selected from 10 consecutive units training in Kenya during 2012 and 2013. The exposure was either doxycycline or mefloquine and the main outcome measure was impact upon ability to work. Each cohort was advised to take doxycycline or mefloquine with exceptions at the individual level where medically or occupationally advised. RESULTS: Significantly more (p < 0.0001) doxycycline users reported that one or more adverse effects had interfered with their ability to do their job than mefloquine users. Of the 867 mefloquine users, who reported on the impact of adverse effects, 109 (12.6%) reported that one or more adverse effects had impacted upon their ability to do their job, compared to 152 (22.2%) of the 685 doxycycline users who had reported on the impact of any adverse effects. Doxycycline symptoms were predominantly gastrointestinal and dermatological, whereas mefloquine symptoms were neuropsychiatric. CONCLUSIONS: Self-reported symptoms were common in those that responded and, while the true background rate of adverse effects (off any medication) is unknown, doxycycline had a significantly increased rate compared with mefloquine and was associated with a greater occupational impact. Therefore, this study supports the view that, for organizations which provide malaria chemoprophylaxis to employees free of charge, mefloquine should be the first-choice antimalarial drug where the only alternative is doxycycline.

Sinus and adenoid inflammation in children with chronic rhinosinusitis and asthma.

BACKGROUND: Chronic rhinosinusitis (CRS) and asthma frequently coexist in children and adults. However, the precise pathophysiologic mechanism of this interaction is still poorly understood, especially in children, owing to the lack of direct measurements of mucosal inflammation in the upper airways. OBJECTIVE: To determine the pathophysiologic mechanism by analyzing the expression of a large array of inflammatory cytokines and chemokines in the sinus and adenoid tissues surgically removed from pediatric patients with CRS refractory to medical management. METHODS: Twenty-eight children 2 to 12 years old diagnosed with CRS with or without asthma and 10 controls were included in this prospective, nonrandomized study. Mucosal expression of 40 inflammatory cytokines was measured with a multiplex assay and was normalized to total tissue protein. RESULTS: Compared with children with CRS and without asthma, children with CRS and asthma had significantly higher sinus levels of tumor necrosis factor-α and adenoid levels of epidermal growth factor, eotaxin, fibroblast growth factor-2, growth-related oncogene, and platelet-derived growth factor-AA. CONCLUSION: The inflammatory response in the upper airway mucosa of children with asthma and CRS was similar, but more severe, compared with children with CRS without asthma. This observation is consistent with the hypothesis that asthma in these patients is caused or exacerbated by severe upper airway disease and supports the concept that treating sinus disease is paramount in the management of chronic asthma in children using, for the first time, direct measurements of airway inflammation in children.

Clinical Outcomes of a Team Approach to Thyroidectomy.

OBJECTIVE: The aim of this study is to assess the rates of thyroidectomy complications performed by two attending surgeons operating together. STUDY DESIGN: This is a retrospective chart review. METHODS: This is a retrospective chart review from September 2008 through October 2013 of thyroidectomy cases performed by the head and neck team at Sanford Health. The primary intervention was the presence of two head and neck attendings during each procedure. Outcomes assessed include rates of temporary and permanent recurrent laryngeal nerve paralysis, and of permanent hypocalcemia. RESULTS: There were 282 patients that underwent a thyroid procedure with a total of 449 at-risk nerves. There were five (1.1 percent) cases of transient vocal cord paresis. There was one case (0.22 percent) of permanent vocal cord paresis after planned nerve resection in a patient with anaplastic thyroid carcinoma. There were no other cases of permanent vocal cord paresis. Of 156 total thyroidectomy cases, there was one case of chronic hypocalcemia (0.64 percent). CONCLUSIONS: A two-surgeon approach to thyroidectomy produces excellent functional outcomes. Further investigation into cost-effectiveness is warranted.

Weight control practices of severely obese patients who are not seeking bariatric surgery.

OBJECTIVE: We sought to better understand why so few severely obese patients undergo bariatric surgery in the United States. DESIGN AND METHODS: We conducted a telephone survey to assess the weight control practices of severely obese patients who were not actively seeking bariatric surgery in Group Health, a health system in Washington State. RESULTS: Among 295 severely obese participants surveyed (63% response rate), most reported actively working on weight loss (58%), although current use of commercial weight loss programs (10%) and obesity pharmacotherapy (0.1%) was low. Household income and white race were strongly associated with lifetime use of commercial programs, suggesting a possible disparity in use of effective treatment for obesity. Many were interested in learning more about bariatric surgery (49%) and pharmacotherapy (53%), but few had ever discussed surgery (26%) or pharmacotherapy (33%) with their physician. Finally, although only 29% had coverage for bariatric surgery, those with coverage were not more likely to have discussed bariatric surgery with their physician. CONCLUSIONS: Overall, our survey of severely obese patients who are not currently seeking bariatric surgery suggests that interest in obesity treatments is high, coverage and receipt of treatment is low, and that there is a potential socioeconomic disparity related to the use of commercial programs.

Sinus balloon catheter dilation after adenoidectomy failure for children with chronic rhinosinusitis.

OBJECTIVE: To assess surgical outcomes in children undergoing sinus balloon catheter dilation for whom previous adenoidectomy has failed. Adenoidectomy is the first line of surgical management for children with chronic rhinosinusitis (CRS). This procedure is successful in about 50 percent of patients. DESIGN: Prospective review of children who had surgery for CRS. SETTING: A referral tertiary health care system. PATIENTS: Children with persistent symptoms after adenoidectomy, despite medical treatment, as documented by the sinonasal 5 (SN-5) score and the Lund-Mackay computed tomography (CT) score. MAIN OUTCOME MEASURE: The SN-5 score at 1 year post procedure. RESULTS: Twenty-six children met the inclusion criteria. The age range was 4 to 12 years (mean [SD] age, 9.0 [2.5] years). The mean (SD) CT score was 7.3 (2.9). The minimum preoperative SN-5 score was 3.0 (mean [SD], 4.6 [0.9]). The mean (SD) time of postoperative follow-up was 13 (3.0) months. The mean (SD) SN-5 score at 1 year was 3.0 (1.2). This was a significant change from preoperative scores (P < .001). Surgical success, measured by a decrease of more than 0.5 on the postoperative SN-5 score, was achieved in 21 children (81%). CONCLUSIONS: Sinus balloon catheter dilation has previously been shown to be safe and effective in children. This current study demonstrates that balloon dilation is effective in children for whom previous adenoidectomy has failed. Balloon catheter dilation may be considered prior to proceeding to functional endoscopic sinus surgery in children with CRS.

Balloon catheter sinuplasty and adenoidectomy in children with chronic rhinosinusitis.

OBJECTIVES: Adenoidectomy is the first step in the surgical management of children with chronic rhinosinusitis (CRS). Adenoidectomy, however, is only effective in half of these children. Although endoscopic sinus surgery is effective for CRS, there is concern for facial growth retardation and major complications. We propose that balloon catheter sinuplasty (BCS) is a minimally invasive, effective procedure in the treatment of pediatric CRS. METHODS: We undertook a nonrandomized, controlled, prospective review of children with failed medical management of CRS who underwent BCS or adenoidectomy. Outcomes were assessed at 1 year of follow-up and were based on SN-5 scores and the need for revision surgery. RESULTS: Forty-nine children who satisfied the inclusion criteria were reviewed. Thirty of the children had BCS. The age range was 4 to 11 years (mean, 7.7 years), and the mean computed tomography score (Lund-Mackay system) was 7.5. Twenty-four of the 30 patients (80%) who underwent BCS showed improvement of their symptoms after 12 months of follow-up, compared with 10 of the 19 patients (52.6%) who underwent adenoidectomy (p < 0.05). A multivariate analysis using logistic regression analysis with age, sex, asthma, and computed tomography score as covariables showed that BCS was also more effective than adenoidectomy in older children. None of the other variables showed statistical significance. CONCLUSIONS: Balloon catheter sinuplasty offers a procedure that is more effective than adenoidectomy and less invasive than endoscopic sinus surgery in the treatment of pediatric CRS.

Correlation between SN-5 and computed tomography in children with chronic rhinosinusitis.

OBJECTIVES/HYPOTHESIS: Symptom score questionnaires for evaluation of chronic rhinosinusitis (CRS) in adults does not correlate with computed tomography (CT) scan scores of paranasal sinuses. The SN-5 is a validated symptom score questionnaire for the evaluation of CRS in children. The purpose of this study is to evaluate the correlation of the SN-5 with the CT score in children. STUDY DESIGN: Retrospective review of prospectively collected data. METHODS: Thirty-two children between the ages of 2 years and 12 years were seen prospectively for symptoms of CRS. The mean age was 7.7 years (range, 3.6-11.5; SD = 2.4). The caretakers completed the SN-5 during their visit when a CT scan of the paranasal sinuses was obtained. RESULTS: The mean SN-5 score was 4.1 (SD = 1.03) and the mean Lund-Mackay CT score was 6.8 (SD = 4.3). There was a significant correlation between the SN-5 score and Lund-MacKay CT score (rho = 0.68; P < .0001) for all children in the study. Twelve (38%) children had asthma, and for those children the correlation was poorer and did not reach statistical significance (rho = 0 .57; P = .057). For nonasthmatics the correlation was stronger (rho = 0.73; P = .0003). CONCLUSIONS: Symptom score questionnaire (SN-5) correlated to the disease severity as measured by the Lund-MacKay CT scan score. This is different from what has been found in adults. These findings have positive implications for the follow-up of treatment of CRS in children because the frequent use of CT scans in children is discouraged due to concern for radiation exposure.

Postischemic infusion of 17-beta-estradiol protects myocardial function and viability.

BACKGROUND: Females demonstrate improved cardiac recovery after ischemia/reperfusion injury compared with males. Attenuation of myocardial dysfunction with preischemic estradiol suggests that estrogen may be an important mediator of this cardioprotection. However, it remains unclear whether post-injury estradiol may have clinical potential in the treatment of acute myocardial infarction. We hypothesize that postischemic administration of 17beta-estradiol will decrease myocardial ischemia/reperfusion injury and improve left ventricular cardiac function. MATERIALS AND METHODS: Adult male Sprague Dawley rat hearts (n = 20) (Harlan, Indianapolis, IN) were isolated, perfused with Krebs-Henseleit solution via Langendorff model, and subjected to 15 min of equilibration, 25 min of warm ischemia, and 40 min reperfusion. Experimental hearts received postischemic 17beta-estradiol infusion, 1 nm (n = 4), 10 nm (n = 4), 25 nm (n = 4), or 50 nm (n = 4), throughout reperfusion. Control hearts (n = 4) were infused with perfusate vehicle. RESULTS: Postischemic recovery of left ventricular developed pressure was significantly greater with 1 nm (51.6% +/- 7.4%) and 10 nm estradiol (47.7% +/- 8.6%) than with vehicle (37.8% +/- 9.7%) at end reperfusion. There was also greater recovery of the end diastolic pressure with 1 nm (47.8 +/- 4.0 mmHg) and 10 nm estradiol (54.0 +/- 4.0) compared with vehicle (75.3 +/- 7.5). Further, 1 nm and 10 nm estrogen preserved coronary flow after ischemia and decreased coronary effluent lactated dehydrogenase compared with controls. Estrogen at 25 nm and 50 nm did not provide additional benefit in terms of functional recovery. Estrogen at all concentrations increased extracellular signal-regulated protein kinase phosphorylation. CONCLUSIONS: Postischemic infusion of 17beta-estradiol protects myocardial function and viability. The attractive potential for the clinical application of postischemic estrogen therapy warrants further study to elucidate the mechanistic pathways and differences between males and females.

High passage number of stem cells adversely affects stem cell activation and myocardial protection.

Progenitor cell plasticity enhances positive remodeling of damaged tissue. We and others have previously shown that progenitor cells may limit apoptosis and modulate inflammation in part by the production of growth factors. However, recent studies suggest that progenitor cells senesce and lose their differentiation potential with increasing time in culture and passage. We hypothesize that murine bone marrow mesenchymal stem cells (MSCs) are cardioprotective against ischemia/reperfusion injury in the isolated perfused rat heart, and that passage number has an adverse effect on MSC activation and cardioprotection. Adult male and female Sprague-Dawley rat hearts were isolated, perfused via Langendorff model, and subjected to ischemia/reperfusion. Mouse MSCs were harvested, cultured, suspended in perfusate, and infused before global index ischemia. Hearts were assigned to controls or infusion with passage 3, 5, or 10 MSCs. In addition, MSCs in culture were stressed by hypoxia and increasing doses of endotoxin (lipopolysaccharide). Mesenchymal stem cell activation was determined by measuring vascular endothelial growth factor production with enzyme-linked immunosorbent assay. All data are reported as mean +/- SEM and were analyzed with 2-way analysis of variance. Differences are considered significant if P < 0.05. Passage 3 murine MSC infusion in hearts before ischemia reduced the depression of left ventricular developed pressure, attenuated the increase of end-diastolic pressure, and reduced the depression of +dP/dT and -dP/dT. However, the MSC protective effect disappeared in hearts infused with passage 5 and passage 10 MSCs. Although hypoxia and lipopolysaccharide resulted in significant activation of MSCs, passage 3 MSCs demonstrated significantly greater vascular endothelial growth factor release than passage 5 and 10 MSCs. Acute murine MSC infusion confers protection in isolated rat hearts. However, high passage number has an adverse effect on MSC activation and protection. This portends limited ex vivo expansion before possible therapeutic use.

Jak/STAT/SOCS signaling circuits and associated cytokine-mediated inflammation and hypertrophy in the heart.

Cytokines are important mediators of cardiac disease. Accumulating evidence indicates that members of the interleukin-6 family of cytokines promote cardiac hypertrophy through the activation of the Janus kinase-signal transducer and activator of transcription (Jak/STAT) pathway. Aberrant Jak/STAT signaling may promote progression from hypertrophy to heart failure. Suppressor of cytokine signaling (SOCS) proteins are underexplored, negative regulators of Jak/STAT signaling. SOCS proteins may also interact with other inflammatory pathways known to affect cardiac function. A better understanding of the therapeutic potential of these proteins may lead to the controlled progression of heart failure and the limitation of myocardial depression. This review summarizes the cardiophysiological effect of the IL-6 cytokine family, outlines the mechanistic pathway of Jak/STAT signaling, explores the regulatory role of SOCS proteins in the heart, and discusses the potential of using SOCS proteins clinically.

Postconditioning in females depends on injury severity.

BACKGROUND: Postconditioning, a series of brief ischemia/reperfusion (I/R) cycles at reperfusion onset, is a recently described novel approach to attenuate I/R injury, and because it is an after-injury treatment strategy, it may have greater clinical potential than preconditioning. However, it has not been determined whether postconditioning is effective in women. MATERIALS AND METHODS: Adult male and female (250-300 g) Sprague-Dawley rat hearts (n = 25) were isolated, perfused via Langendorff model, and subjected to 15 min of equilibration, 20 or 25 min of global index ischemia (37 degrees C), and 40 min total reperfusion. Postconditioned hearts were subjected to 6 cycles of 10-s reperfusion/10-s ischemia immediately after release of the global index ischemia. Hearts were assigned randomly to one of four groups: 1) control hearts, 20 min index ischemia; 2) postconditioned hearts, 20 min index ischemia; 3) control hearts, 25 min index ischemia; or 4) postconditioned hearts, 25 min index ischemia. All data are reported as mean +/- SEM and were analyzed with unpaired student's t test; P < 0.05 considered significant. RESULTS: Postconditioning in female rats after 20 min of ischemia reduced depression of left ventricular-developed pressure (93.9 +/- 6.7% postconditioning recovery versus 58.6 +/- 12.6% control recovery, P < 0.05), attenuated the increase of end-diastolic pressure (P < 0.05), and reduced the depression of +dP/dT and -dP/dT (P < 0.05). The postconditioning protective effect disappeared in female rats exposed to 25 min of ischemia. The postconditioning protective effect was observed in male rats after both 20 min and 25 min ischemia. CONCLUSIONS: Postconditioning confers cardioprotection in leukocyte-free, buffer-perfused female hearts, but this protection may depend on ischemia duration. The attractive potential for the clinical application of postconditioning, however, warrants further studies to elucidate the mechanistic pathways and differences in males and female rats.