Early Retinal Microvascular Changes Assessed with Swept-Source OCT Angiography in Type 1 Diabetes Patients without Retinopathy.

Type 1 diabetes is a chronic disease that can lead to vision loss when diabetic retinopathy develops. Retinal microvascular alterations occur before the appearance of clinical signs on a fundus examination. This study aimed to analyze retinal vascular parameters on optical coherence tomography angiography (OCT-A) in patients with type 1 diabetes without diabetic retinopathy in comparison with non-diabetic volunteers. This cross-sectional study was conducted at Dijon University Hospital from 2018 to 2020. Vascular densities were measured using macular OCT-A. In total, 98 diabetes patients and 71 non-diabetic volunteers were enrolled. A statistically significant lower vascular density of the inner circle was found in the superficial capillary plexus (SCP) in the diabetes group (p < 0.01). There was a statistically significant correlation between central vascular density in the deep capillary plexus (DCP) and total daily insulin intake (p = 0.042); furthermore, use of the FreeStyle Libre (FSL) device was associated with higher vascular densities in both the SCP (p = 0.034 for outer circle density) and DCP (p < 0.01 for inner circle density and p = 0.023 for outer circle density). Retinal microvascularization was early-altered in type 1 diabetes, and using the FSL device seemed to preserve retinal microvascularization.

Segmentation of the aorta in systolic phase from 4D flow MRI: multi-atlas vs. deep learning.

OBJECTIVE: In the management of the aortic aneurysm, 4D flow magnetic resonance Imaging provides valuable information for the computation of new biomarkers using computational fluid dynamics (CFD). However, accurate segmentation of the aorta is required. Thus, our objective is to evaluate the performance of two automatic segmentation methods on the calculation of aortic wall pressure. METHODS: Automatic segmentation of the aorta was performed with methods based on deep learning and multi-atlas using the systolic phase in the 4D flow MRI magnitude image of 36 patients. Using mesh morphing, isotopological meshes were generated, and CFD was performed to calculate the aortic wall pressure. Node-to-node comparisons of the pressure results were made to identify the most robust automatic method respect to the pressures obtained with a manually segmented model. RESULTS: Deep learning approach presented the best segmentation performance with a mean Dice similarity coefficient and a mean Hausdorff distance (HD) equal to 0.92+/- 0.02 and 21.02+/- 24.20 mm, respectively. At the global level HD is affected by the performance in the abdominal aorta. Locally, this distance decreases to 9.41+/- 3.45 and 5.82+/- 6.23 for the ascending and descending thoracic aorta, respectively. Moreover, with respect to the pressures from the manual segmentations, the differences in the pressures computed from deep learning were lower than those computed from multi-atlas method. CONCLUSION: To reduce biases in the calculation of aortic wall pressure, accurate segmentation is needed, particularly in regions with high blood flow velocities. Thus, the deep learning segmen-tation method should be preferred.

Efficacy, safety, and cost of pomalidomide in relapsed and refractory multiple myeloma.

OBJECTIVES: To investigate the efficacy, safety, and cost of a pomalidomide-dexamethasone regimen in patients with relapsed and refractory multiple myeloma (RRMM). METHODS: All patients (n = 63) treated with pomalidomide-dexamethasone for RRMM in our university hospital between August 2013 and October 2015 were included. RESULTS: Pomalidomide was discontinued early due to progression (before the 4th cycle) in 17 (27%) patients. No case was discontinued for intolerance. The only independent factor that predicted early pomalidomide discontinuation was time from diagnosis to pomalidomide initiation <3 years. Overall response rate was 51% including complete response in 8%, very good partial response in 25%, and partial response in 19% patients. Thirteen (33%) patients showed stable disease. Median overall survival was 6.4 months in the 17 patients who discontinued pomalidomide early vs 26.8 months in the 14 patients with stable disease vs not achieved in the 32 responders (log-rank; P < 10-3 ). The most common grade ≥3 adverse events were neutropenia (14%) and infections (25%). The incremental cost-effectiveness ratio of pomalidomide-dexamethasone compared with dexamethasone alone was estimated at €39 911 per life-year gained. CONCLUSIONS: The study demonstrated that pomalidomide-dexamethasone regimen has a long-term favorable safety-efficacy profile in RRMM patients. The survival benefit is substantial even in patients with stable disease.

Medicoeconomic analysis of lobectomy using thoracoscopy versus thoracotomy for lung cancer: a study protocol for a multicentre randomised controlled trial (Lungsco01).

INTRODUCTION: In the last decade, video-assisted thoracoscopic surgery (VATS) lobectomy for non-small cell lung cancer (NSCLC) has had a major effect on thoracic surgery. Retrospective series have reported benefits of VATS when compared with open thoracotomy in terms of postoperative pain, postoperative complications and length of hospital stay. However, no large randomised control trial has been conducted to assess the reality of the potential benefits of VATS lobectomy or its medicoeconomic impact. METHODS AND ANALYSIS: The French National Institute of Health funded Lungsco01 to determine whether VATS for lobectomy is superior to open thoracotomy for the treatment of NSCLC in terms of economic cost to society. This trial will also include an analysis of postoperative outcomes, the length of hospital stay, the quality of life, long-term survival and locoregional recurrence. The study design is a two-arm parallel randomised controlled trial comparing VATS lobectomy with lobectomy using thoracotomy for the treatment of NSCLC. Patients will be eligible if they have proven or suspected lung cancer which could be treated by lobectomy. Patients will be randomised via an independent service. All patients will be monitored according to standard thoracic surgical practices. All patients will be evaluated at day 1, day 30, month 3, month 6, month 12 and then every year for 2 years thereafter. The recruitment target is 600 patients. ETHICS AND DISSEMINATION: The protocol has been approved by the French National Research Ethics Committee (CPP Est I: 09/06/2015) and the French Medicines Agency (09/06/2015). Results will be presented at national and international meetings and conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02502318.

Non-dominant hand quicker to insert peripheral venous catheters under echographic guidance: A randomised trial.

BACKGROUND: Ultrasound guidance for venous catheter placement requires the use of both hands. An accurate and stable ultrasound image is fundamental for obtaining good quality images, consequently permitting accurate needle placement. We hypothesized that the dominant hand could be used to perform echography, leaving the non-dominant hand available for peripheral venous catheter (PVC) insertion. METHODS: Prospective, open-label, randomized, crossover study. Group 1 inserted the PVC with the dominant hand, and held the probe with the non-dominant hand in a first series of 20 insertions, and vice versa in a second series of 20 insertions performed 11days later. Group 2 punctured with the non-dominant hand in Series 1 and vice versa in series 2. The study population comprised female student nurses (aged 20-30years) who had learned neither ultrasound techniques nor catheter insertion. The primary endpoint was time to successful puncture. We recorded age, sex, video game use, and the laterality of hands, feet and eyes. RESULTS: One left-handed and nine right-handed nurses were randomized to each group. Puncture by the non-dominant hand was significantly quicker in both series (P<0.001). There was no difference between groups for time to successful puncture with the dominant hand; however a significant difference was found for the non-dominant hand (P<0.01). According to multivariate analysis, the time to successful puncture was significantly lower when the non-dominant hand was used to puncture (adjusted difference 5.6s, P<0.0001). CONCLUSION: Using the dominant hand to hold the ultrasound probe and the non-dominant hand to puncture and insert the catheter achieves successful insertion in a significantly shorter time.

Preclinical Study of Single-Dose Moxidectin, a New Oral Treatment for Scabies: Efficacy, Safety, and Pharmacokinetics Compared to Two-Dose Ivermectin in a Porcine Model.

BACKGROUND: Scabies is one of the commonest dermatological conditions globally; however it is a largely underexplored and truly neglected infectious disease. Foremost, improvement in the management of this public health burden is imperative. Current treatments with topical agents and/or oral ivermectin (IVM) are insufficient and drug resistance is emerging. Moxidectin (MOX), with more advantageous pharmacological profiles may be a promising alternative. METHODOLOGY/PRINCIPAL FINDINGS: Using a porcine scabies model, 12 pigs were randomly assigned to receive orally either MOX (0.3 mg/kg once), IVM (0.2 mg/kg twice) or no treatment. We evaluated treatment efficacies by assessing mite count, clinical lesions, pruritus and ELISA-determined anti-S. scabiei IgG antibodies reductions. Plasma and skin pharmacokinetic profiles were determined. At day 14 post-treatment, all four MOX-treated but only two IVM-treated pigs were mite-free. MOX efficacy was 100% and remained unchanged until study-end (D47), compared to 62% (range 26-100%) for IVM, with one IVM-treated pig remaining infected until D47. Clinical scabies lesions, pruritus and anti-S. scabiei IgG antibodies had completely disappeared in all MOX-treated but only 75% of IVM-treated pigs. MOX persisted ~9 times longer than IVM in plasma and skin, thereby covering the mite's entire life cycle and enabling long-lasting efficacy. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate that oral single-dose MOX was more effective than two consecutive IVM-doses, supporting MOX as potential therapeutic approach for scabies.

De-escalation chemotherapy and hematological profiles in patients with advanced Hodgkin's lymphoma.

BACKGROUND: There is a need to develop treatment strategies that are less toxic than BEACOPPescalated x6 cycles, the standard-of-care in advanced Hodgkin's lymphoma patients. OBJECTIVE: To compare short-term hematological toxicity in advanced Hodgkin's lymphoma patients treated with either BEACOPPescalated x6 cycles (standard group) or BEACOPPescalated x2 followed by ABVD x4 cycles (experimental group). METHOD: In 27 patients, we compared injections of erythropoiesis stimulating agent and granulocyte colony-stimulating factor, transfusions, hospitalization days, as well as hemoglobin, platelet, leukocyte levels. Method In 27 patients, we compared injections of erythropoiesis stimulating agent and granulocyte colony-stimulating factor, transfusions, hospitalization days, as well as hemoglobin, platelet, leukocyte levels. RESULTS: The mean number of erythropoiesis stimulating agent and granulocyte colony-stimulating factor injections, platelet transfusions and hospitalization days was significantly lower in the experimental group (erythropoiesis stimulating agents: mean difference -6.6 ± 2.4, p = 0.005; granulocyte colony-stimulating factors: mean difference -8.3 ± 3.6, p = 0.020, platelet transfusions: mean difference -0.6 ± 0.3, p = 0.035; hospitalization days: mean difference: -8.5 ± 1.7 days, p < 10(-3)). There were no differences in terms of red cell transfusions, platelet counts or leukocyte levels between the two groups. From the 3rd chemotherapy cycle, hemoglobin levels decreased to a significantly lesser extent in the experimental group. CONCLUSION: We demonstrated an overall better short-term hematological profile in advanced Hodgkin's lymphoma patients who received a de-escalation chemotherapy regimen with significant differences mainly in terms of hemoglobin levels, erythropoiesis stimulating agent injections, and hospitalization days.

Pulse Wave Transit Time Measurements of Cardiac Output in Septic Shock Patients: A Comparison of the Estimated Continuous Cardiac Output System with Transthoracic Echocardiography.

BACKGROUND: We determined reliability of cardiac output (CO) measured by pulse wave transit time cardiac output system (esCCO system; COesCCO) vs transthoracic echocardiography (COTTE) in mechanically ventilated patients in the early phase of septic shock. A secondary objective was to assess ability of esCCO to detect change in CO after fluid infusion. METHODS: Mechanically ventilated patients admitted to the ICU, aged >18 years, in sinus rhythm, in the early phase of septic shock were prospectively included. We performed fluid infusion of 500 ml of crystalloid solution over 20 minutes and recorded CO by EsCCO and TTE immediately before (T0) and 5 minutes after (T1) fluid administration. Patients were divided into 2 groups (responders and non-responders) according to a threshold of 15% increase in COTTE in response to volume expansion. RESULTS: In total, 25 patients were included, average 64±15 years, 15 (60%) were men. Average SAPSII and SOFA scores were 55±21.3 and 13±2, respectively. ICU mortality was 36%. Mean cardiac output at T0 was 5.8±1.35 L/min by esCCO and 5.27±1.17 L/min by COTTE. At T1, respective values were 6.63 ± 1.57 L/min for esCCO and 6.10±1.29 L/min for COTTE. Overall, 12 patients were classified as responders, 13 as non-responders by the reference method. A threshold of 11% increase in COesCCO was found to discriminate responders from non-responders with a sensitivity of 83% (95% CI, 0.52-0.98) and a specificity of 77% (95% CI, 0.46-0.95). CONCLUSION: We show strong correlation esCCO and echocardiography for measuring CO, and change in CO after fluid infusion in ICU patients.

Usefulness and limitations of contractile reserve evaluation in patients with low-flow, low-gradient aortic stenosis eligible for cardiac resynchronization therapy.

AIMS: In low-flow, low-gradient aortic stenosis (LF/LG AS), the assessment of contractile reserve (CR) by dobutamine stress echocardiography (DSE) is recommended for risk stratification and treatment strategy. However, DSE may show limitations in cases of left ventricular dyssynchrony (LVD). The impact of LVD in LF/LG AS, and the feasibility of CRT in this setting have never been evaluated. We aimed to assess: (i) the proportion of LF/LG AS patients with LVD; (ii) the influence of LVD on CR at DSE; and (iii) the effects of CRT in these patients. METHODS AND RESULTS: Thirty consecutive patients with LF/LG AS underwent DSE with study of CR. The operative risk for aortic valve replacement (AVR) was assessed using the logistic EuroSCORE. Twenty-one of the 30 patients had LVD. They were significantly older, more symptomatic, had a higher EuroSCORE, and a lower prevalence of CR than those with a narrow QRS (47% vs. 100%, P = 0.009). A CRT pacemaker was implanted in 19 of the 21 patients with LVD. All 19 (except for one patient who died suddenly) experienced significant clinical and echocardiographic improvement. Fourteen CRT patients underwent subsequent AVR with a low event rate. Four CRT patients refused AVR; two of them worsened again 1-2 years post-CRT. CONCLUSION: LVD is common in LF/LG AS patients and may be a major mechanism of afterload mismatch, as well as a cause of underdetection of CR. CRT in this population is feasible and may be proposed as a bridge to surgery.

Predictive factors of transarterial chemoembolisation toxicity in unresectable hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolisation (TACE) is an effective treatment for unresectable hepatocellular carcinoma (HCC), but can cause severe toxicity. AIM: To identify predictive factors of severe TACE-related toxicity in patients with unresectable HCC. METHODS: All HCC patients who underwent TACE at the Dijon University Hospital between 2008 and 2011 were included in this retrospective study. Severe TACE-related toxicity was defined as the occurrence of any adverse event grade ≥ 4, or any adverse event that caused a prolongation of hospitalisation of >8 days, or any additional hospitalisation within 1 month after TACE. Factors predicting toxicity were identified using a logistic regression model. The robustness of the final model was confirmed using bootstrapping (500 replications). RESULTS: 124 patients were included, median age was 67 years and 90% were male; 22 patients (18%) experienced severe TACE-related toxicity. Factors that independently predicted severe TACE-related toxicity in multivariate analysis were total tumour size (OR, 1.15 cm(-1); 95%CI, 1.04-1.26; p=0.01), and high serum AST levels (OR, 1.10 per 10 IU/l; 95%CI, 1.01-1.21; p=0.04). The results were confirmed by bootstrapping. CONCLUSIONS: Total tumour size and high serum AST levels were predictive factors of severe TACE-related toxicity in this hospital-based series of patients with unresectable HCC.

Aichi virus IgG seroprevalence in Tunisia parallels genomic detection and clinical presentation in children with gastroenteritis.

Aichi virus has been described as a novel causative agent of gastroenteritis in humans. In this study, we report the seroprevalence distribution of Aichi virus in Tunisia. A panel of 1,000 sera was screened by applying an enzyme-linked immunosorbent assay for immunoglobulin G specific for Aichi virus. A considerable prevalence (92%) of antibody to Aichi virus was found across all age groups. The specific anti-Aichi virus antibodies increased with age, from a high rate (68.8%) in children under 10 years old to about 100% in persons more than 60 years old. We found a statistically significant increase in levels of antibody to Aichi virus according to the age of patients. Immunoglobulin M antibodies were detected among five children. A high frequency of Aichi virus monoinfections in hospitalized children with severe gastroenteritis was previously observed in Tunisia. Aichi virus causes diarrhea with dehydration, fever, and vomiting. This work is the first to establish a correlation between the high seroprevalence of specific Aichi virus antibodies, clinical presentation, and a high frequency of isolation of Aichi virus by genomic characterization in stools of children suffering from gastroenteritis. Our data show the importance and emerging character of Aichi virus in the viral etiology of pediatric gastroenteritis.

Seroprevalence distribution of Aichi virus among a French population in 2006-2007.

Little is known about the epidemiology of Aichi virus, which is a new member of the family Picornaviridae, in the genus Kobuvirus. We report here on seroprevalence in France. Sera were screened using an enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G. Of 972 sera tested, seroprevalence ranged from 25% for the 7-month-to-9-year-old age group to about 85% for the 30-to-39-year-old age group and older age groups. Our ELISA correlated well with the microneutralization technique. This study shows that Aichi virus is quite frequent in France and that seroconversion occurs before the age of 40.

Plasma antioxidant status in septic critically ill patients: a decrease over time.

Severe septic states in humans are responsible for intense intravascular oxidative stress, which induces numerous adaptive mechanisms. We determined time sequence changes in total plasma antioxidant capacity (TAC) and major plasma antioxidant concentrations, which have not been fully explained in septic conditions. A cohort of 56 consecutive septic patients (septic shock n = 37, severe sepsis n = 19) and six healthy volunteers. We compared TAC and antioxidant levels in patients with one of two degrees of septic states, at the onset of illness, to those of healthy volunteers. Thereafter, over a 10-day follow-up, we observed daily the time sequence changes of the two septic populations in terms of TAC and antioxidants. At the onset, there was no difference between the three groups in terms of TAC values (healthy subjects 2.18 +/- 0.04; severe sepsis 2.03 +/- 0.07; septic shock 2.09 +/- 0.09), then an equivalent time decline was observed in the two septic populations whatever the severity. TAC was statistically linked to uric acid, proteins in particular albumin and bilirubin (multivariate analysis), but no correlation was found with any vitamin (A, C and E). A sharp and persistent decrease in vitamin C concentrations was underlined. TAC, unaffected at first, deteriorated over time whatever the severity of the infection in these critically ill patients. TAC, unable to distinguish severe sepsis and septic shock, is unlikely to be a particularly useful outcome measure.

Candida spp. colonization significance in critically ill medical patients: a prospective study.

OBJECTIVE: Multiple-site colonization with Candida species is commonly recognized as a major risk factor for invasive fungal infection in critically ill patients. The fungal colonization density could be of predictive value for the diagnosis of systemic candidiasis in high-risk surgical patients. Little is known about it in the medical ICU setting. DESIGN AND SETTING: Prospective observational study in the eight-bed medical intensive care unit of a teaching hospital. SUBJECTS: 92 consecutive nonneutropenic patients hospitalized for more than 7 days. MEASUREMENTS AND RESULTS: The colonization index (ratio of the number of culture-positive surveillance sites for Candida spp. to the number of sites cultured) was calculated weekly upon ICU admission until death or discharge. The 0.50 threshold was reached in 36 (39.1%) patients, almost exclusively in those with detectable fungal colonization upon ICU admission. The duration of broad-spectrum antibiotic therapy was found to be the main factor that independently promoted fungal growth as measured through the colonization index. CONCLUSIONS: Candida spp. multiple-site colonization is frequently met among the critically ill medical patients. Broad-spectrum antibiotic therapy was found to promote fungal growth in patients with prior colonization. Since most of the invasive candidiasis in the ICU setting are thought to be subsequent to colonization in high-risk patients, reducing antibiotic use could be useful in preventing fungal infections.

Candidemia in critically ill patients: difference of outcome between medical and surgical patients.

OBJECTIVE: Candidemia is increasingly encountered in critically ill patients with a high fatality rate. The available data in the critically ill suggest that patients with prior surgery are at a higher risk than others. However, little is known about candidemia in medical settings. The main goal of this study was to compare features of candidemia in critically ill medical and surgical patients. DESIGN: Ten-year retrospective cohort study (1990-2000). SETTING: Medical and surgical intensive care units (ICUs) of a teaching hospital. PATIENTS: Fifty-one patients with at least one positive blood culture for Candida species. MAIN RESULTS: Risk factors were retrieved in all of the patients: central venous catheter (92.1%), mechanical ventilation (72.5%), prior bacterial infection (70.6%), high fungal colonization index (45.6%). Candida albicans accounts for 55% of all candidemia. The overall mortality was 60.8% (85% and 45.2% in medical and surgical patients, respectively). Independent factors associated with survival were prior surgery (hazard ratio [HR] =0.25; 0.09-0.67 95% confidence interval [CI], p<0.05), antifungal treatment (HR =0.11; 0.04-0.30 95% CI, p<0.05) and absence of neutropenia (HR =0.10; 0.02-0.45 95% CI, p<0.05). Steroids, neutropenia and high density of fungal colonization were more frequently found among medical patients compared to surgical ones. CONCLUSIONS: Candidemia occurrence is associated with a high mortality rate among critically ill patients. Differences in underlying conditions could account for the poorer outcome of the medical patients. Screening for fungal colonization could allow identification of such high-risk patients and, in turn, improve outcome.

Comparison of a computer based method and the classical manual method for radiographic joint space width assessment in hip osteoarthritis.

OBJECTIVE: To compare the intraobserver reliability and the sensitivity to change of 2 techniques evaluating the cartilage breakdown in hip osteoarthritis (OA). DESIGN: 3 year longitudinal study. PARTICIPANTS: patients with painful hip OA. OUTCOME: coxofemoral joint space width (JSW) at baseline and at 3 year followup was measured on anteroposterior weight-bearing radiographs by 2 methods: a manual method to obtain JSW at the narrowest point (minimal JSW) using a 0.1 mm graduated magnifying glass and a computer based method to obtain minimal and average JSW. STATISTICAL ANALYSIS: Two assessments, at one month interval, of each pair of films; evaluation of the intraobserver reliability using the intraclass coefficient of correlation, and the Bland and Altman approach, obtaining the smallest detectable difference (SDD). For each technique, percentage of progressors was evaluated, i.e., the percentage of patients with change greater than the SDD. Evaluation of sensitivity to change was performed using the standardized response mean (SRM), with 95% CI calculated using the jackknife method. RESULTS: Twenty-five pairs of films were evaluated. There were no statistically significant differences between the 3 analyses in the calculated intraclass coefficients of correlation, percentage of progressors, or SRM. CONCLUSION: These results suggest that both techniques are reliable and sensitive enough to detect changes in a relevant percentage of patients with hip OA after a 3 year followup.

[Risk factors for the acquisition of Pseudomonas aeruginosa in a surgical intensive care unit]. / Facteurs de risque d'acquisition de Pseudomonas aeruginosa dans un service de réanimation chirurgicale et traumatologique.

OBJECTIVES: To investigate the risk factors for the acquisition (infection and/or colonization) of Pseudomonas aeruginosa, which is frequently associated with nosocomial infections, in a surgical intensive care unit in Dijon. METHOD: A retrospective case-control study was performed on 57 cases matching with 114 controls, between December 1996 and February 1999. The statistical method used was a conditional multiple logistic regression model. RESULTS: Three groups of variables were studied (patient characteristics--invasive procedures--previous administration of antibiotics). The multiple logistic regression analysis confirmed 3 risk factors: duration of sedation, infection with another bacteria and cranio-encephalic trauma. These factors are commonly involved in nosocomial infections. CONCLUSION: This study confirms the interest of infection control measures and the prevention of nosocomial infections, especially in cranio-encephalic trauma. The hypothetical relationship between acquisition of Pseudomonas aeruginosa and previous administration of antibiotics was not confirmed. A more powerful study would perhaps specify this relationship.