Significant amounts of oxygen free radicals (oxidants) are generated during cerebral ischemia/reperfusion, and oxidative stress plays an important role in brain damage after stroke. In addition to ...oxidizing macromolecules, leading to cell injury, oxidants are also involved in cell death/survival signal pathways and cause mitochondrial dysfunction. Experimental data from laboratory animals that either overexpress (transgenic) or are deficient in (knock-out) antioxidant proteins, mainly superoxide dismutase, have provided strong evidence of the role of oxidative stress in ischemic brain damage. In addition to mitochondria, recent reports demonstrate that NADPH oxidase (NOX), an important pro-oxidant enzyme, is also involved in the generation of oxidants in the brain after stroke. Inhibition of NOX is neuroprotective against cerebral ischemia. We propose that superoxide dismutase and NOX activity in the brain is a major determinant for ischemic damage/repair and that these major anti- and pro-oxidant enzymes are potential endogenous molecular targets for stroke therapy.
Purpose
To explore the ability of intraoperative specimen radiography (SR) to correctly identify positive margins in patients receiving breast conserving surgery (BCS). To assess whether the ...reoperation rate can be reduced by using this method.
Methods
This retrospective study included 470 consecutive cases receiving BCS due to a primarily diagnosed breast cancer. SR was carried out in two planes, assessing the specimen regarding the presence of the lesion and its relation to all margins. If indicated, re-excision of selective orientations was advised. Under consideration of gross inspection and the SR-findings, it was up to the surgeon whether to perform re-resections. The recommendations for re-excision were, separately for each orientation, compared to the histopathological results, serving as gold standard.
Results
Intraoperative SR was performed in 470 cases, thus 2820 margins were assessed. Of those, 2510 (89.0%) were negative and 310 (11.0%) positive. SR identified 2179 (77.3%) margins correctly as negative, whereas 331 (11.7%) clear margins were misjudged as positive. Of 310 infiltrated margins, SR identified 114 (4.0%) correctly, whereas 196 (7.0%) infiltrated margins were missed. This resulted in a sensitivity/specificity of 36.8%/86.8% and PPV/NPV of 25.6%/91.8%. Through targeted re-resections positive margins could be reduced by 31.0% 310 to 214 (7.6%). On case level, the rate of secondary procedures could be reduced by 37.0% from 162 to 102 (21.7%).
Conclusions
SR is a helpful tool to identify infiltrated margins and to reduce the rate of secondary surgeries by recommending targeted re-excisions of according orientations in order to obtain a final negative margin status.
Objective
To describe obstetrical care and in‐hospital outcomes in very preterm triplet pregnancies in a European multiregional cohort.
Methods
Data from a prospective population‐based study of very ...preterm births between 22 + 0 and 31 + 6 weeks of gestation in 19 regions from 11 European countries participating in the EPICE project in 2011/2012 were used to describe triplet pregnancies and compare them with twins and singletons.
Results
Triplets constituted 1.1% of very preterm pregnancies (97/8851) and 3.3% of very preterm live births (258/7900); these percentages varied from 0% to 2.6% and 0% to 6% respectively across the regions. In‐hospital mortality after live birth was 12.4% and did not differ significantly from singletons or twins or by birth order. However, 28.9% of mothers with a triplet pregnancy experienced at least one neonatal death. Ninety percent of live‐born triplets were delivered by cesarean. Vaginal delivery was associated with an Apgar score of less than 7, but not with in‐hospital mortality.
Conclusions
The prevalence of very preterm triplets varies across European regions. Most triplets were born by cesarean and those born vaginally had lower Apgar scores. Overall, in‐hospital mortality after live birth was similar to singletons and twins.
European very preterm triplets had similar neonatal outcomes to twins and singletons; most were delivered by cesarean; vaginal delivery was associated with lower Apgar scores.
Agranulocytosis is a rare and serious adverse effect of antithyroid drugs, with unknown etiology. The present study aimed to uncover genetic susceptibility and underlying mechanisms of antithyroid ...drug‐induced agranulocytosis (ATDAC). We studied two independent families with familial Graves' disease, of which several members developed ATDAC. In addition, six sporadic ATDAC patients with Graves' disease were investigated. Whole exome sequencing analysis of affected and unaffected family members was performed to identify genetic susceptibility variants for ATDAC, followed by functional characterization of primary granulocytes from patients and unrelated healthy controls. Whole exome sequencing, cosegregation analysis, and stringent selection criteria of candidate gene variants identified NOX3 as a genetic factor related to ATDAC. Functional studies revealed increased apoptosis of methimazole‐treated granulocytes from patients carrying NOX3 variants. In conclusion, genetic variants in NOX3 may confer susceptibility to antithyroid drug‐induced apoptosis of granulocytes. These findings contribute to the understanding of the mechanisms underlying ATDAC.
Follow-up of very preterm infants is essential for reducing risks of health and developmental problems and relies on parental engagement. We investigated parents' perceptions of post-discharge ...healthcare for their children born very preterm in a European multi-country cohort study.
Data come from a 5-year follow-up of an area-based cohort of births <32 weeks' gestation in 19 regions from 11 European countries. Perinatal data were collected from medical records and 5-year data from parent-report questionnaires. Parents rated post-discharge care related to their children's preterm birth (poor/fair/good/excellent) and provided free-text suggestions for improvements. We analyzed sociodemographic and medical factors associated with poor/fair ratings, using inverse probability weights to adjust for attrition bias, and assessed free-text responses using thematic analysis.
Questionnaires were returned for 3635 children (53.8% response rate). Care was rated as poor/fair for 14.2% from 6.1% (France) to 31.6% (Denmark); rates were higher when children had health or developmental problems (e.g. cerebral palsy (34.4%) or epilepsy (36.9%)). From 971 responses, 4 themes and 25 subthemes concerning care improvement were identified.
Parents' experiences provide guidance for improving very preterm children's post-discharge care; this is a priority for children with health and developmental problems as parental dissatisfaction was high.
In a European population-based very preterm birth cohort, parents rated post-discharge healthcare as poor or fair for 14.2% of children, with a wide variation (6.1-31.6%) between countries. Dissatisfaction was reported in over one-third of cases when children had health or developmental difficulties, such as epilepsy or cerebral palsy. Parents' free-text suggestions for improving preterm-related post-discharge healthcare were similar across countries; these focused primarily on better communication with parents and better coordination of care. Parents' lived experiences are a valuable resource for understanding where care improvements are needed and should be included in future research.
Computed tomography (CT)-guided percutaneous radiofrequency ablation (RFA) has become a commonly used procedure in the treatment of liver tumors. One of the main challenges related to the method is ...the exact placement of the instrument within the lesion. To address this issue, a system was developed for computer-assisted needle placement which uses a set of fiducial needles to compensate for organ motion in real time. The purpose of this study was to assess the accuracy of the system in vivo. Two medical experts with experience in CT-guided interventions and two nonexperts used the navigation system to perform 32 needle insertions into contrasted agar nodules injected into the livers of two ventilated swine. Skin-to-target path planning and real-time needle guidance were based on preinterventional
1
mm
CT data slices. The lesions were hit in 97% of all trials with a mean user error of
2.4
±
2.1
mm
, a mean target registration error (TRE) of
2.1
±
1.1
mm
, and a mean overall targeting error of
3.7
±
2.3
mm
. The nonexperts achieved significantly better results than the experts with an overall error of
2.8
±
1.4
mm
(
n
=
16
)
compared to
4.5
±
2.7
mm
(
n
=
16
)
. The mean time for performing four needle insertions based on one preinterventional planning CT was
57
±
19
min
with a mean setup time of
27
min
, which includes the steps fiducial insertion
(
24
±
15
min
)
, planning CT acquisition
(
1
±
0
min
)
, and registration
(
2
±
1
min
)
. The mean time for path planning and targeting was
5
±
4
and
2
±
1
min
, respectively. Apart from the fiducial insertion step, experts and nonexperts performed comparably fast. It is concluded that the system allows for accurate needle placement into hepatic tumors based on one planning CT and could thus enable considerable improvement to the clinical treatment standard for RFA procedures and other CT-guided interventions in the liver. To support clinical application of the method, optimization of individual system modules to reduce intervention time is proposed.
There is an increasing demand for peptide-mimicking molecules to modulate the interactions between proteins of pharmaceutical and agrochemical interest and their target polypeptides. Unnatural ...L-alpha-amino acids differing from the 20 naturally proteinogenic amino acids only in their side chain are ideal for this purpose, but their chemical synthesis is complex. Here we describe a fermentation-based approach for biosynthesis of unnatural amino acids after re-engineering the cysteine-biosynthetic pathway in Escherichia coli. O-acetylation of serine, the committed step of the pathway, was released from feedback inhibition by mutating the serine acetyltransferase gene. Next, the naturally broad substrate specificity of O-acetylserine sulfhydrylase was exploited for the direct in vivo incorporation of an unnatural side chain in a semisynthetic fermentation process comparable to the production of beta-lactams. O-acetyl-L-serine extruded from the cells by way of the O-acetylserine efflux protein was amenable to further biotransformations.
Context:
Besides short stature and gonadal dysgenesis, Turner syndrome (TS) is associated with various abnormalities. Adults with TS have a reduced life expectancy, mainly related to structural ...abnormalities of the heart and aorta, and an increased risk of atherosclerosis.
Objective:
Our objective was to investigate the yield of an initial standardized multidisciplinary screening in adult TS patients.
Design and Setting:
This was an observational study at a multidisciplinary care unit for adult women with TS.
Participants:
Participants were adult women with TS (n = 150). Mean age was 31.0 ± 10.4 yr, with 47% karyotype 45,X.
Interventions:
All women were consulted by an endocrinologist, a gynecologist, a cardiologist, an otorhinolaryngologist, and when indicated, a psychologist. The screening included magnetic resonance imaging of the heart and aorta, echocardiography, electrocardiogram, dual-energy x-ray absorptiometry, renal ultrasound, audiogram, and laboratory investigations according to international expert recommendations.
Main outcome measures:
New diagnoses and prevalence of TS-associated morbidity were evaluated.
Results:
Thirty percent of patients currently lacked medical follow-up, and 15% lacked estrogen replacement therapy in the recent last years. The following disorders were newly diagnosed: bicuspid aortic valve (n = 13), coarctation of the aorta (n = 9), elongation of the transverse aortic arch (n = 27), dilation of the aorta (n = 34), osteoporosis (n = 8), osteopenia (n = 56), renal abnormalities (n = 7), subclinical hypothyroidism (n = 33), celiac disease (n = 3), glucose intolerance (n = 12), dyslipidemia (n = 52), hypertension (n = 39), and hearing loss warranting a hearing aid (n = 8). Psychological consultation was needed in 23 cases.
Conclusions:
Standardized multidisciplinary evaluation of adult women with TS as advocated by expert opinion is effective and identifies significant morbidity. Girls with TS benefit from a careful transition to ongoing adult medical care.
Background
Apart from animal testing and clinical trials, surgical research and laparoscopic training mainly rely on phantoms. The aim of this project was to design a phantom with realistic anatomy ...and haptic characteristics, modular design and easy reproducibility. The phantom was named open-source Heidelberg laparoscopic phantom (OpenHELP) and serves as an open-source platform.
Methods
The phantom was based on an anonymized CT scan of a male patient. The anatomical structures were segmented to obtain digital three-dimensional models of the torso and the organs. The digital models were materialized via rapid prototyping. One flexible, using an elastic abdominal wall, and one rigid method, using a plastic shell, to simulate pneumoperitoneum were developed. Artificial organ production was carried out sequentially starting from raw gypsum models to silicone molds to final silicone casts. The reproduction accuracy was exemplarily evaluated for ten silicone rectum models by comparing the digital 3D surface of the original rectum with CT scan by calculating the root mean square error of surface variations. Haptic realism was also evaluated to find the most realistic silicone compositions on a visual analog scale (VAS, 0–10).
Results
The rigid and durable plastic torso and soft silicone organs of the abdominal cavity were successfully produced. A simulation of pneumoperitoneum could be created successfully by both methods. The reproduction accuracy of ten silicone rectum models showed an average root mean square error of 2.26 (0–11.48) mm. Haptic realism revealed an average value on a VAS of 7.25 (5.2–9.6) for the most realistic rectum.
Conclusion
The OpenHELP phantom proved to be feasible and accurate. The phantom was consecutively applied frequently in the field of computer-assisted surgery at our institutions and is accessible as an open-source project at
www.open-cas.org
for the academic community.
PDF
