Intraoperative blood loss during decompressive craniectomy for intractable intracranial hypertension after severe traumatic brain injury in children

Purpose

There are no data available on the risk of intraoperative bleeding during decompressive craniectomy (DC) after traumatic brain injury (TBI) in children. The objectives of this study were to assess the risk of intraoperative bleeding during DC for intractable intracranial hypertension after TBI, to identify potential factors associated with the risk of bleeding during DC, and to assess the impact of DC on systemic and cerebral hemodynamics and on coagulation.

Methods

Twelve children were identified as having undergone DC after TBI from April 2009 to June 2013 in our center. Subjects were allocated into two groups according to the percentage of blood loss (IBL) during the intraoperative period (<or ≥50 % of the estimated blood volume (EBV)).

Results

The median IBL during DC was 49 [17–349] % of the EBV. Children with an IBL?≥?50 % of EBV had higher preoperative intracranial pressure (ICP) (p?=?0.03) and international normalized ratio (INR) (p?=?0.02) than those with an IBL?<?50 % of EBV. DC induced significant decreases in ICP (p?=?0.0005), mean arterial pressure (p?=?0.01), and a significant increase in norepinephrine flow rate (p?=?0.04) between the immediate pre- and postoperative periods.

Conclusions

DC allows a significant decrease in ICP after severe pediatric TBI but is a surgical procedure at a high risk of bleeding. High ICP and INR during the immediate preoperative period are the main factors associated with increased IBL during DC. Further studies are needed to confirm our results and to assess the impact of the amount of IBL on the postoperative survival and functional outcome.     

Clinical oxygen enhancement ratio of tumors in carbon ion radiotherapy: the influence of local oxygenation changes

The effect of carbon ion radiotherapy on hypoxic tumors has recently been questioned because of low linear energy transfer (LET) values in the spread-out Bragg peak (SOBP). The aim of this study was to investigate the role of hypoxia and local oxygenation changes (LOCs) in fractionated carbon ion radiotherapy. Three-dimensional tumors with hypoxic subvolumes were simulated assuming interfraction LOCs. Different fractionations were applied using a clinically relevant treatment plan with a known LET distribution. The surviving fraction was calculated, taking oxygen tension, dose and LET into account, using the repairable–conditionally repairable (RCR) damage model with parameters for human salivary gland tumor cells. The clinical oxygen enhancement ratio (OER) was defined as the ratio of doses required for a tumor control probability of 50% for hypoxic and well-oxygenated tumors. The resulting OER was well above unity for all fractionations. For the hypoxic tumor, the tumor control probability was considerably higher if LOCs were assumed, rather than static oxygenation. The beneficial effect of LOCs increased with the number of fractions. However, for very low fraction doses, the improvement related to LOCs did not compensate for the increase in total dose required for tumor control. In conclusion, our results suggest that hypoxia can influence the outcome of carbon ion radiotherapy because of the non-negligible oxygen effect at the low LETs in the SOBP. However, if LOCs occur, a relatively high level of tumor control probability is achievable with a large range of fractionation schedules for tumors with hypoxic subvolumes, but both hyperfractionation and hypofractionation should be pursued with caution.     

Primary immunodeficiencies in cytosolic pattern-recognition receptor pathways: Toward host-directed treatment strategies

In the last decade, the paradigm of primary immunodeficiencies (PIDs) as rare recessive familial diseases that lead to broad, severe, and early-onset immunological defects has shifted toward collectively more common, but sporadic autosomal dominantly inherited isolated defects in the immune response. Patients with PIDs constitute a formidable area of research to study the genetics and the molecular mechanisms of complex immunological pathways. A significant subset of PIDs affect the innate immune response, which is a crucial initial host defense mechanism equipped with pattern-recognition receptors. These receptors recognize pathogen- and damage-associated molecular patterns in both the extracellular and intracellular space. In this review, we will focus on primary immunodeficiencies caused by genetic defects in cytosolic pattern-recognition receptor pathways. We discuss these PIDs organized according to their mutational mechanisms and consequences for the innate host response. The advanced understanding of these pathways obtained by the study of PIDs creates the opportunity for the development of new host-directed treatment strategies.     

Molecular variants of human papilloma virus 16 E2, E4, E5, E6 and E7 genes associated with cervical neoplasia in Romanian patients

The aim of this study was to identify and associate the sequence variations of human Papillomavirus 16 (HPV16) genes from women who live in two different areas of Romania and associate them with malignant progression. One hundred twenty-four HPV16-positive cervical isolates were collected, and the E2, E4, E5, E6 and E7 viral genes were sequenced. Two new missense mutations in the E6 gene (C279G and A305C) were found (together or alone, in association with other mutations) in 44 of 124 cases. The most frequently simultaneously mutated genes were E4/E2 hinge, E5 and E6 (p = 0.0004) in squamous cell carcinoma (SCC) samples. Also, for SCC patients, the best-correlated mutation patterns were obtained for E4/E2 hinge-E5 (r = 0.7984; p < 0.0001). No sample was found to have all of the investigated viral genes concurrently mutated. Phylogenetic analysis was performed to characterize the viral variants. Similar results were found for SCC and cervical intraepithelial neoplasia III (CINIII) cases. After all of the target gene sequences were assembled, all patients were found to be infected with viruses of the HPV16- European-German (EG) lineage, and two clusters were identified, the first (55/96 variants) from Moldavia and the second (41/96 variants) from Bucharest. The distinct cluster derived from EG in Moldavia could partially explain the increased frequency of SCC in this area. This study has generated a comprehensive set of sequence variation data on HPV16 circulating in Romania to join the existing data and highlight the important role of HPV16 variants during cervical carcinogenesis.     

BCG-induced trained immunity in NK cells: Role for non-specific protection to infection

Adaptive features of innate immunity, also termed ‘trained immunity’, have recently been shown to characterize monocytes of BCG vaccinated healthy volunteers. Trained immunity leads to increased cytokine production in response to non-related pathogens via epigenetic reprogramming of monocytes. Recently, memory-like properties were also observed in NK cells during viral infections, but it is unknown if memory properties of NK cells contribute to trained immunity due to BCG vaccination.     

Simultaneous detection of As and Se in polyester resin skin phantoms

It is known that As and Se act as metabolic antagonists. Hence, an improvement in assessing As-related health risks can be achieved by simultaneous quantitative measurements of both As and Se levels in the human body. In this paper, the simultaneous detection of trace concentrations of As and Se in polyester resin skin phantoms was demonstrated. The experiments were performed with a commercial miniature X-ray tube and silicon PiN detector X-ray fluorescence (XRF) system. No significant overlap between the K_α peaks of the two elements was observed. Minimum detection limits of (1.05±0.02) μg As g^?1 and (0.88±0.02) μg Se g^?1 were found.