Fetal cerebellar growth and Sylvian fissure maturation: international standards from Fetal Growth Longitudinal Study of INTERGROWTH-21st Project.

OBJECTIVE: To construct international ultrasound-based standards for fetal cerebellar growth and Sylvian fissure maturation. METHODS: Healthy, well nourished pregnant women, enrolled at < 14 weeks' gestation in the Fetal Growth Longitudinal Study (FGLS) of INTERGROWTH-21st , an international multicenter, population-based project, underwent serial three-dimensional (3D) fetal ultrasound scans every 5 ± 1 weeks until delivery in study sites located in Brazil, India, Italy, Kenya and the UK. In the present analysis, only those fetuses that underwent developmental assessment at 2 years of age were included. We measured the transcerebellar diameter and assessed Sylvian fissure maturation using two-dimensional ultrasound images extracted from available 3D fetal head volumes. The appropriateness of pooling data from the five sites was assessed using variance component analysis and standardized site differences. For each Sylvian fissure maturation score (left or right side), mean gestational age and 95% CI were calculated. Transcerebellar diameter was modeled using fractional polynomial regression, and goodness of fit was assessed. RESULTS: Of those children in the original FGLS cohort who had developmental assessment at 2 years of age, 1130 also had an available 3D ultrasound fetal head volume. The sociodemographic characteristics and pregnancy/perinatal outcomes of the study sample confirmed the health and low-risk status of the population studied. In addition, the fetuses had low morbidity and adequate growth and development at 2 years of age. In total, 3016 and 2359 individual volumes were available for transcerebellar-diameter and Sylvian-fissure analysis, respectively. Variance component analysis and standardized site differences showed that the five study populations were sufficiently similar on the basis of predefined criteria for the data to be pooled to produce international standards. A second-degree fractional polynomial provided the best fit for modeling transcerebellar diameter; we then estimated gestational-age-specific 3rd , 50th and 97th smoothed centiles. Goodness-of-fit analysis comparing empirical centiles with smoothed centile curves showed good agreement. The Sylvian fissure increased in maturation with advancing gestation, with complete overlap of the mean gestational age and 95% CIs between the sexes for each development score. No differences in Sylvian fissure maturation between the right and left hemispheres were observed. CONCLUSION: We present, for the first time, international standards for fetal cerebellar growth and Sylvian fissure maturation throughout pregnancy based on a healthy fetal population that exhibited adequate growth and development at 2 years of age. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Differential prognostic accuracy of right ventricular dysfunction, the Seattle heart failure model and the MAGGIC score in patients with severe mitral regurgitation undergoing the MitraClip® procedure.

BACKGROUND: MitraClip ® (MC) is an established procedure for severe mitral regurgitation (MR) in patients deemed unsuitable for surgery.Right ventricular dysfunction (RVD) is associated with a higher mortality risk. The prognostic accuracy of heart failure risk scores like the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in pts undergoing MC with or without RVD has not been investigated so far. METHODS: SHFM and MAGGIC score were calculated retrospectively. RVD was determined as tricuspid annular plane systolic excursion (TAPSE) ≤15 mm. Area under receiver operating curves (AUROC) of SHFM and MAGGIC were performed for one-year all-cause mortality after MC. RESULTS: N = 103 pts with MR III° (73 ± 11 years, LVEF 37 ± 17%) underwent MC with a reduction of at least I° MR. One-year mortality was 28.2%.In Kaplan-Meier analysis, one- year mortality was significantly higher in RVD-pts (34.8% vs 2.8%, p = 0.009).Area under the Receiver Operating Characteristic (AUROC) for SHFM and MAGGIC were comparable for both scores (SHFM: 0.704, MAGGIC: 0.692). In pts without RVD, SHFM displayed a higher AUROC and therefore better diagnostic accuracy (SHFM: 0.776; MAGGIC: 0.551, p < 0.05). In pts with RVD, MAGGIC and SHFM displayed comparable AUROCs. CONCLUSION: RVD is an important prognostic marker in pts undergoing MC. SHFM and MAGGIC displayed adequate over-all prognostic power in these pts. Accuracy differed in pts with and without RVD, indicating higher predictive power of the SHFM score in pts without RVD.

[Out-of-hospital airway management with a laryngeal tube or endotracheal intubation for out-of-hospital cardiac arrest : Influence on in-hospital mortality]. / Präklinisches Atemwegsmanagement mit Larynxtubus oder Endotrachealtubus bei präklinischem Herz-Kreislauf-Stillstand : Einfluss auf die Krankenhausmortalität.

BACKGROUND: Endotracheal (ET) intubation has been the gold standard in out-of-hospital airway management for a long time. Recent guidelines suggest an alternative airway management with supraglottic airway devices like the laryngeal tube (LT) especially for less experienced rescue personnel. However, scientific evidence on the prognostic impact of the laryngeal tube in the setting of cardiopulmonary resuscitation is limited. METHODS: We aimed to compare mortality outcomes in out-of-hospital cardiac arrest (OHCA) patients after preclinically initiated airway management with either ET or LT in a propensity score matched, single-center retrospective analysis. RESULTS: A total of 208 patients with OHCA were resuscitated and intubated with either ET (n = 160; 77%) or LT (n = 48; 23%) in the urban area of Frankfurt am Main, Germany, and treated thereafter on the intensive care unit of the University Hospital Frankfurt from 2006-2014. In-hospital mortality was 84% versus 85% in the ET and LT group (p = 0.86). No difference regarding in-hospital mortality has been observed between the two airway management techniques in univariate as well as in multivariate mortality analysis (HR = 0.98, 95% confidence interval [CI] 0.69-1.39; p = 0.92; adjusted HR = 1.01, 95% CI 0.76-1.56; p = 0.62). To adjust for potential confounders, propensity score matching was additionally performed resulting in a cohort of 120 matched patients in a 3:1 ratio (ET:LT). Again, survival to hospital discharge was comparable between the two patient groups (propensity-adjusted HR = 0.99, 95% CI 0.65-1.51, p = 0.97). Further, preclinical airway management with LT or ET showed no difference in mortality within first 24 h (propensity-adjusted HR = 1.02; 95% CI 0.44-2.36; p = 0.96). CONCLUSION: Preclinical airway management with LT shows similar mortality outcomes in direct comparison to intubation with ET in OHCA patients. Further randomized studies are warranted.

Contrary roles of IL-4 and IL-12 on IL-10 production and proliferation of human tumour reactive T cells.

The cytokine profile of tumour reactive T cells is likely to play a central role in their function. However, little is known about how cytokine patterns of tumour reactive T cells can be regulated. Here, the authors investigated the influence of exogenous regulatory cytokines in addition to interleukin-2 (IL-2) on cytokine patterns and the proliferation of T cells recognizing an autologous sarcoma cell line. In this system, IL-4 and IL-12 showed the most polarizing influences on tumour reactive T cells. Exogenous IL-4 induced a predominant production of IL-4 while decreasing the interferon-gamma (IFN-gamma) and IL-10 production by tumour reactive T cells. It also stimulated the growth of tumour reactive CD4+ T cell clones. In contrast, IL-12 substantially increased the production of IL-10 and IFN-gamma. This was accompanied by a growth inhibition of tumour reactive T cells. The growth of CD4+ tumour reactive T cells was also suppressed by exogenous IL-10. This study shows that cytokine patterns and proliferation tumour reactive T cells can be significantly influenced by exogenous cytokines and confirms the hypothesis of a negative feedback loop of IL-12 by the induction of IL-10 in the context of human tumour reactive T cells.

Specificities and functions of CD4+ HLA class II-restricted T cell clones against a human sarcoma: evidence for several recognized antigens.

CD4+ T cells play an important role for tumor immunity in animal tumor models, yet there are few reports about the role of CD4+ HLA class II-restricted T cells in the immune response against human tumors. Against a human sarcoma exclusively CD4+, T cell clones could be established. These T cell clones were cytotoxic and secreted TNF and additional cytokines in response to the IFN-gamma-treated, HLA class II-positive autologous sarcoma cells. Several Ags were recognized by representative T cell clones: an Ag presented by HLA-DR and specific for the sarcoma; Ags presented by both HLA-DR alleles of the sarcoma, HLA-DR4 and -15, and shared by allogenic HLA-DR matched cell lines of different tissue lineages, including B cell blasts; and a sarcoma Ag presented by HLA-DP or DQ. Cytokine profiles of sarcoma-reactive T cell clones were dependent on the cytokine environment present during establishment of the T cell clones. The addition of exogenous IL-4 shifted the cytokine patterns of sarcoma-reactive T cell clones from Th1-like patterns to Th0/Th2-like patterns and decreased IL-10 production. TNF, IFN-gamma, IL-4, and supernatants of T cell clones induced HLA-DR expression on the sarcoma cells and, thus, were able to enhance Ag presentation. This autologous T cell response to a human sarcoma represents a new model for HLA class II-restricted T cell responses to human tumors.