Preventing vaccinia virus class-I epitopes presentation by HSV-ICP47 enhances the immunogenicity of a TAP-independent cancer vaccine epitope

Herpes simplex virus protein ICP47, encoded by US12 gene, strongly downregulates major histocompatibility complex (MHC) class-I antigen restricted presentation by blocking transporter associated with antigen processing (TAP) protein. To decrease viral vector antigenic immunodominance and MHC class-I driven clearance, we engineered recombinant vaccinia viruses (rVV) expressing ICP47 alone (rVV-US12) or together with endoplasmic reticulum (ER)-targeted Melan-A/MART-1(27-35) model tumor epitope (rVV-MUS12). In this study, we show that antigen presenting cells (APC), infected with rVV-US12, display a decreased ability to present TAP dependent MHC class-I restricted viral antigens to CD8+ T-cells. While HLA class-I cell surface expression is strongly downregulated, other important immune related molecules such as CD80, CD44 and, most importantly, MHC class-II are unaffected. Characterization of rVV-MUS12 infected cells demonstrates that over-expression of a TAP-independent peptide, partially compensates for ICP47 induced surface MHC class-I downregulation (30% vs. 70% respectively). Most importantly, in conditions where clearance of infected APC by virus-specific CTL represents a limiting factor, a significant enhancement of CTL responses to the tumor epitope can be detected in cultures stimulated with rVV-MUS12, as compared to those stimulated by rVV-MART alone. Such reagents could become of high relevance in multiple boost protocols required for cancer immunotherapy, to limit vector-specific responsiveness.     

The outcome for pediatric patients on peritoneal dialysis

BACKGROUND: The adverse effects of peritonitis and of the duration of dialysis on dialysis adequacy and clinical outcome were evaluated in this study. METHODS: The study comprised 24 chronic peritoneal dialysis patients who were followed up at least for 12 months. Casual blood pressure (BP) measurements, echocardiographic evaluation, peritonitis rate, hemoglobin (Hb), serum albumin, normalized protein catabolic rate (nPCR), total Kt/Vurea, weekly creatinine clearance (CCr), residual renal function (RRF), removal of fluid and dose of recombinant human erythropoietin (EPO) were evaluated. RESULTS: Mean age of the patients was 15.3 +/- 3.6 years. Mean follow-up was 50.4 +/- 26.8 months. Peritonitis rate was calculated as 1 episode/32.7 patient-months. Systolic hypertension was detected in 14 patients (58%) and diastolic hypertension in 15 (63%). RRF showed a negative correlation with duration on dialysis (r=-0.623, p=0.006).There was no significant correlation between RRF and nPCR, Hb, hematocrit, albumin and dose of EPO. A negative correlation was found with left ventricular mass index and fluid removal (r=-0.461, p=0.041). Higher doses of Kt/Vurea are associated with higher protein intake (r=0.503, p=0.024). A positive correlation was found between Kt/Vurea and Hb and Hct levels (r=0.460, p=0.009, and r=0.528, p=0.017, respectively). Dialysis adequacy tests were found not to be affected by the frequency of peritonitis. CONCLUSION: The most important factor for the prevention of hypervolemia in chronic peritoneal dialysis patients is RRF. The concept of adequate dialysis should include normal volume homeostasis, control of blood pressure and adequate nutrition.     

Air-Q the Intubating Laryngeal Airway: Comparative study of hemodynamic stress responses to tracheal intubation via Air-Q and direct laryngoscopy

Background: Tracheal intubation is the gold standard for securing airway. Tracheal intubation through DLS produces marked hemodynamic stress responses. The Air-Q is a new supraglottic airway device. The purpose of this study was to determine whether endotracheal intubation through Air-Q is associated with lesser hemodynamic stress responses.Methods: 60 patients scheduled for elective surgery under general anesthesia requiring endotracheal intubation were randomly assigned into two groups. Direct laryngoscopy group and Air-Q group. Blood pressure and heart rate were recorded before, after induction, immediately after intubation and every minute for 4 min after intubation. The intubation time was recorded. Upon removal of the Air-Q, trauma to the upper airway was reported.Results: The intubation time was shorter in the DLS group compared with the Air-Q group (P value < 0.05). A significant reduction in BP was evident after the induction of anesthesia in both groups. Immediately after intubation, there was a significant increase in BP compared with the preintubation values. A decline was inspected between 1 and 4 min postintubation in both groups with significant difference immediately, at 1 and 2 min postintubation between the two groups. There were significant increase in HR immediately, at 1 and 2 min postintubation compared with the preintubation values, but there was no significant difference at each time point between two groups. Sore throat was more in the Air-Q group (P value <0.05).Conclusion: The hemodynamic stress response to intubation by Air-Q is less than that of DLS despite the longer duration of the former.     

Apparent diffusion coefficient values of mediastinal masses in children

Objective

Compare apparent diffusion coefficient (ADC) values between benign and malignant mass lesions in a cohort of children referred for imaging of a mediastinal mass.

Material and methods

Prospective study including 24 consecutive children (11 boys, 13 girls aged 5 months to 16 years). All underwent echo planar diffusion weighted MR imaging of the mediastinum with b-factors of 0 and 600 s/mm². Apparent diffusion coefficient (ADC) values were calculated and correlated with the surgical finding or biopsy.

Results

The mean ADC value of malignant mediastinal tumors was 0.91 (S.D., 0.17) ×10⁻³ mm²/s and of benign lesions 1.8 (S.D., 0.33) ×10⁻³ mm²/s. There was significant different in the ADC value between malignant tumors and benign mediastinal tumors (P < 0.001). Selection of 1.2 × 10⁻³ mm²/s as a threshold value for differentiating malignant from benign mediastinal masses has an accuracy of 93%, sensitivity of 92%, specificity of 94%, positive predictive value of 94%, negative predictive value of 92% and area under the curve of 0.962.

Conclusion

Apparent diffusion coefficient value is a promising non-invasive parameter for assessment of mediastinal mass in children.     

A retrospective evaluation of critically ill patients infected with H1N1 influenza A virus in Bursa,Turkey, during the 2009–2010 pandemic

Background

H1N1 influenza A virus infections were first reported in April 2009 and spread rapidly, resulting in mortality worldwide. The aim of this study was to evaluate patients with H1N1 infection treated in the intensive care unit (ICU) in Bursa, Turkey.

Methods

Demographic characteristics, clinical features, and outcome relating to H1N1 infection were retrospectively analysed in patients treated in the ICU.

Results

Twenty-three cases of H1N1 infection were treated in the ICU. The mean age of patients was 37 years range: (17–82). Fifteen patients were female (65.2%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score was 19 range: (5–39). The most common symptoms were dyspnea (73.9%), fever (69.6%), and cough (60.9%). Mechanical ventilation was required for all patients. Oseltamivir and antibiotics were administered to all patients. Six (26.1%) patients died. APACHE II scores were higher in the deceased 28.5 range: [16–39] vs. 14 range: [5–28] in survivors; p = 0.013).

Conclusion

When compared to the literature, the demographic, epidemiological, and clinical characteristics were similar in the cases we encountered. The mortality rate was high despite the use of appropriate treatment. We believe that the high mortality is related to higher APACHE II scores. The H1N1 virus should be considered in community acquired pneumonia, especially in younger patients presenting with severe pneumonia.     

Interpretation of RNFLT values in multiple sclerosis‐associated acute optic neuritis using high‐resolution SD‐OCT device

Purpose: Optical coherence tomography (OCT) has emerged as the technique of choice in measuring the retinal nerve fibre layer (RNFL) quantitatively. It is suggested that RNFL reduction may correlate with lesion burden and diffuse axonal degeneration in the whole CNS of patients with multiple sclerosis (MS). However, RNFL changes because of optic neuritis (ON) must be taken into account. Methods: Twenty‐three patients with acute ON (46 eyes) associated with clinical definite MS (23 ON eyes, 23 fellow eyes) and 23 sex‐ and age‐matched healthy controls were studied. Retinal nerve fibre layer thickness (RNFLT) was measured at baseline, using a high‐resolution spectral domain OCT (SD‐OCT) applying circular, peripapillary OCT scans with a novel eye‐tracking mechanism. Results: The internal OCT software was able to identify RNFL atrophy in three out of five of the acute ON eyes and one out of four of the fellow eyes with previous ON episodes. Retinal nerve fibre layer thickness of two ON (8.7%) and five fellow eyes (21.7%) was overestimated, thus located within the 95% and 5% confidence interval of the company standard values (not marked pathologic). In contrast, our comparison with age‐ and sex‐matched controls revealed RNFL atrophy suggestive of prior, clinically silent RNFL loss in ON and fellow eyes (30.4%). Conclusion: Retinal nerve fibre layer thickness measurements at a single time‐point seem to have a limited role in detecting prior clinically silent optic nerve injury. Our data suggest that affected eyes should be compared with the fellow eyes and a sufficient number of age‐ and sex‐matched controls to allow the detection of even subtle RNFL changes at baseline. The role of OCT for disease monitoring of MS must be evaluated in detail, as ON is often the initial symptom of MS.