Observations on the arterial baroreflex in neurally mediated vasodepressor syncope

The arterial baroreflex was studied in subjects who had recently had an episode of vasodepressor syncope. This was determined using 2–3 mcg/kg intravenous boluses of phenylephrine and assessing the bradycardic response. The values were measured in ms/mmHg and expressed as the angular coefficient of the regression line between the increase in R—R interval on the electrocardiograph and the systolic arterial pressure. In subjects examined immediately after the vasodepressor syncope episode the bradycardic response was much more marked than in controls (p < 0.01) and in the subjects themselves 6 months after the episode, provided that they were symptom-free (p < 0.01). It is concluded that in vasodepressor syncope there is a phase in which the baroreflex is highly sensitive and that this is due not to a lowering of the stimulation threshold but to a gain in the efferent arc, which explains a vagotonic response.     

Prognostic role of the recepteur d'origine nantais (RON) expression in ovarian cancer patients

ObjectiveThe aim of the study was to investigate the potential clinical relevance of immunohistochemically assessed RON expression in a large, single institution series of primary untreated advanced ovarian cancer patients.MethodsImmunohistochemical analysis was performed by using the polyclonal rabbit anti-RON-β antibody (C-20, clone sc-322, Santa Cruz, California). Results were expressed as the total proportion of immunostained tumor cells (RON positivity), or the percentage of cells showing strong staining of RON expression (H-RON positivity).ResultsIn the overall series RON positive immunoreaction was observed in 103/141 cases, while H-Ron positivity was detected in 577141 (40.4%) cases. No association between RON and H-RON expression with response to first-line treatment was documented. During the follow up period, progression and death of disease were observed in 111 (78.7%) and 76 (53.9%) cases, respectively. Cases with strong H-RON expression has a shorter overall survival (median = 35 months) than cases with low RON levels (median = 59 months) (X² = ? 2.1, p value = 0.032). In multivariate analysis, only platinum resistance, and extent of residual tumor retained an independent negative prognostic role for OS, with the percentages of H-RON positively immunostained cells showing a borderline statistical significance (p value = 0.0643). The unfavourable role of elevated percentages of H-RON expression was maintained only in the subgroup of platinum resistant recurrent ovarian cancer patients (X² = 3.89, p value = 0.048) compared to the platinum sensitive ones (X² = 1.98, p value = 0.16).ConclusionsThe assessment of RON expression deserves further attention as a parameter helpful to identify poor prognosis ovarian cancer patients potentially candidates to investigational agents.     

WAGR syndrome: is the 'R' always justified?

Although mild-to-moderate intellectual disability is usually considered part of WAGR syndrome (Wilms' tumour (WT), Aniridia, Genital abnormalities, and metal Retardation, due to 11p13 deletion) the neuropsychological profile of the syndrome is little reported in the literature. We report about a 12-year-old boy presenting with WAGR syndrome (WT, right complete aniridia, bilateral cryptorchidism, interstitial deletion involving band 11p13) but with no mental retardation. An in-depth clinical evaluation revealed no behavioural or social problems and the child's neuropsychological profile was found to be within the normal range for all abilities and functions investigated (with the exception of an impulsive cognitive style and some difficulties in academic skills). This case underlines the importance of in-depth neuropsychological evaluation that includes not only IQ measurement, but also examination of attention and academic skills, in order to establish the complete phenotypical profile of WAGR patients, rather than labelling them as learning disabled (i.e. mental retardation).     

Dual IGF1R/IR inhibitors in combination with GD2-CAR T-cells display a potent anti-tumor activity in diffuse midline glioma H3K27M-mutant

BackgroundDiffuse midline gliomas (DMG) H3K27M-mutant, including diffuse intrinsic pontine glioma (DIPG), are pediatric brain tumors associated with grim prognosis. Although GD2-CAR T-cells demonstrated significant anti-tumor activity against DMG H3K27M-mutant in vivo, a multimodal approach may be needed to more effectively treat patients. We investigated GD2 expression in DMG/DIPG and other pediatric high-grade gliomas (pHGG) and sought to identify chemical compounds that would enhance GD2-CAR T-cell anti-tumor efficacy.MethodsImmunohistochemistry in tumor tissue samples and immunofluorescence in primary patient-derived cell lines were performed to study GD2 expression. We developed a high-throughput cell-based assay to screen 42 kinase inhibitors in combination with GD2-CAR T-cells. Cell viability, western blots, flow-cytometry, real time PCR experiments, DIPG 3D culture models, and orthotopic xenograft model were applied to investigate the effect of selected compounds on DIPG cell death and CAR T-cell function.ResultsGD2 was heterogeneously, but widely, expressed in the tissue tested, while its expression was homogeneous and restricted to DMG/DIPG H3K27M-mutant cell lines. We identified dual IGF1R/IR antagonists, BMS-754807 and linsitinib, able to inhibit tumor cell viability at concentrations that do not affect CAR T-cells. Linsitinib, but not BMS-754807, decreases activation/exhaustion of GD2-CAR T-cells and increases their central memory profile. The enhanced anti-tumor activity of linsitinib/GD2-CAR T-cell combination was confirmed in DIPG models in vitro, ex vivo, and in vivo.ConclusionOur study supports the development of IGF1R/IR inhibitors to be used in combination with GD2-CAR T-cells for treating patients affected by DMG/DIPG and, potentially, by pHGG.     

Failure to read motor intentions from gaze in children with autism

A core feature of autism is the abnormal use of gaze to attribute mental states to others, and thus to predict others' behaviour. An untested idea is whether this dysfunction is confined to mental states having a propositional content, such as beliefs and desire or extends to motor intentional states which allow one to make inferences about the actions of others. This study used kinematics to examine the ability to use gaze to inform one about the motor states of another in normal and autistic children. In each trial two participants, a model and an observer, were seated facing each other at a table. In three experimental blocks the model was requested to grasp a stimulus, to gaze towards the same stimulus, and to gaze away from the stimulus without performing any action. The task for the observer was to grasp the stimulus after having watched the model perform her task. We observed that normal children showed facilitation effects in terms of movement speed following the observation of the model grasping or simply gazing at the object. In contrast, autistic children did not show any evidence of facilitation in these conditions. Neither normal nor autistic children showed evidence of facilitation when the model's gaze was not directed towards the stimulus. These findings demonstrate that, in contrast to normal children, children with autism fail to use information from the model's action or gaze to plan their subsequent action, and that in autism the inability to use of another person's gaze produces a lack of understanding of the motor intention of others.     

Implications of acute kidney injury after heart transplantation: what a surgeon should know

Objective: Data regarding risks and consequences of acute kidney injury (AKI) after cardiac transplantation are dismissingly few and unclear. This study defined the incidence, risk factors and prognostic implication of AKI in a single-center cohort operated on between January 1999 and December 2008. Methods: Data from 307 consecutive recipients (mean age: 47.42 ± 13.58, 20.5% female, 18.9% diabetics, 19.5% with previous cardiac operations, 26.4% hospitalized, 78.4 ± 33.7 ml min⁻¹ preoperative glomerular filtration rate (eGFR)) were analyzed using multivariable logistic regression modeling. AKI was defined according to RIFLE (Risk, Injury, and Failure; and Loss, and End-stage kidney disease) criteria. Results: RIFLE scores of I or F were detected in 14%, and continuous venovenous hemofiltration was needed in 6.1%. Risk factors for AKI were: previous cardiac operation (odds ratio (OR) 2.35; 95% confidence interval (CI), 1.11–4.9), blood transfusion (OR 1.08; 95% CI, 1.011–1.16), troponin I release >10 (OR 1.031; 95% CI, 1.001–1.064), length of ischemic time (OR 1.008; 95% CI, 1.011–1.16). Overall hospital mortality averaged 7.8% and overall 1-year mortality was 10.4%; both mortality rates increased with each RIFLE stratification (Normal 3.4%, RIFLE R = 7.1%; RIFLE I = 25.7%; and RIFLE F = 37.5% and Normal 5.6%, RIFLE R = 11.8%, RIFLE I = 25.7%, and RIFLE F = 37.5%, respectively). AKI proved independent predictors of both early and 1-year mortality. The burden of AKI significantly affected 1-year kidney function (Δ preoperative GFR − 1-year GFR in AKI vs no AKI = −25.872 ± 22.54 vs −7.968 ± 34.18, p = 0.015). Conclusions: AKI is a highly prevalent and prognostically important complication. Some of the risk factors for AKI identified may be modifiable.     

Emergency Sleeve Gastrectomy as Rescue Treatment for Acute Gastric Necrosis Due to Type II Paraesophageal Hernia in an Obese Woman with Gastric Banding

A morbidly obese 42-year-old woman presented with a 1-week history of left chest pain. She had undergone laparoscopic adjustable gastric banding 16 months earlier with a body mass index (BMI) of 49.2 kg/m². Diagnostic workup revealed a large left pleural empyema and ruled out band slippage. At left thoracotomy, a misdiagnosed type II paraesophageal strangulated hernia with gastric necrosis and large perforation of the fundus was evident. At laparotomy, the band was removed, the stomach was reduced into the abdomen, and a sleeve gastrectomy was performed. Her postoperative course was uneventful, and 6 months after surgery, her BMI is 31 kg/m². Emergency sleeve gastrectomy could represent a good option to treat, at the same time and in a safe way, both gastric necrosis and paraesophageal hernia, improving the good results in terms of weight loss after gastric restriction from gastric banding.     

Air-Filled vs Water-Filled Intragastric Balloon: a Prospective Randomized Study

Background

The positioning of an intragastric saline-filled balloon has been developed as temporary and reversible therapeutic option for treatment of morbid obesity. Recently, an air-filled balloon was also developed. The aim of this study is to prospectively compare these two devices in terms of weight loss parameters, safety, and tolerance.

Methods

Sixty patients were randomized into two groups: group A (Bioenterics Intragastric Balloon?CBIB; n?=?30; 20?F/10?M, mean age 36.7?±?10.9; mean BMI 46.5?±?5.9) and group B (Endobag-Heliosphere; n?=?30; 20?F/10?M, mean age 37.8?±?10.6; mean BMI 46.1?±?5.6). All patients of both groups were sedated with midazolam (5?mg)?+?Propofol (2?mg/kg i.v.). The Heliosphere Bag was air-filled with 950?ml while BIB? was inflated with 500?ml of saline and 10?ml of methylene blue. Percentage of excess weight loss (%EWL) and body mass index (BMI) were evaluated. Student t test, Fisher exact test, and ?? ² test were used for statistical analysis.

Results

Similar weight loss parameters were observed in patients treated with liquid or air-filled balloon at time of removal: mean BMI was 40.8?±?6.2 and 41.9?±?6.5(p?=?ns), and mean %EWL was 20?±?12 and 18?±?14 (p?=?ns) in groups A and B, respectively. Significant longer extraction time, with high patient discomfort, was observed in group B due to difficult passage through the cardia and the lower pharynx.

Conclusions

Air-filled balloon can be another valid therapeutic option in the temporary treatment of obesity, but at this time, the quality of the device must be improved to ameliorate the patient compliance at removal and avoid the spontaneous deflations.