Adjuvant Use of PlasmaJet Device During Cytoreductive Surgery for Advanced-Stage Ovarian Cancer: Results of the PlaComOv-study, a Randomized Controlled Trial in The Netherlands.

OBJECTIVE: Standard surgical treatment of advanced-stage ovarian carcinoma with electrosurgery cannot always result in complete cytoreductive surgery (CRS), especially when many small metastases are found on the mesentery and intestinal surface. We investigated whether adjuvant use of a neutral argon plasma device can help increase the complete cytoreduction rate. PATIENTS AND METHODS: 327 patients with FIGO stage IIIB-IV epithelial ovarian cancer (EOC) who underwent primary or interval CRS were randomized to either surgery with neutral argon plasma (PlasmaJet) (intervention) or without PlasmaJet (control group). The primary outcome was the percentage of complete CRS. The secondary outcomes were duration of surgery, blood loss, number of bowel resections and colostomies, hospitalization, 30-day morbidity, and quality of life (QoL). RESULTS: Complete CRS was achieved in 119 patients (75.8%) in the intervention group and 115 patients (67.6%) in the control group (risk difference (RD) 8.2%, 95% confidence interval (CI) -0.021 to 0.181; P = 0.131). In a per-protocol analysis excluding patients with unresectable disease, complete CRS was obtained in 85.6% in the intervention group and 71.5% in the control group (RD 14.1%, 95% CI 0.042 to 0.235; P = 0.005). Patient-reported QoL at 6 months after surgery differed between groups in favor of PlasmaJet surgery (95% CI 0.455-8.350; P = 0.029). Other secondary outcomes did not differ significantly. CONCLUSIONS: Adjuvant use of PlasmaJet during CRS for advanced-stage ovarian cancer resulted in a significantly higher proportion of complete CRS in patients with resectable disease and higher QoL at 6 months after surgery. (Funded by ZonMw, Trial Register NL62035.078.17.) TRIAL REGISTRATION: Approved by the Medical Ethics Review Board of the Erasmus University Medical Center Rotterdam, the Netherlands, NL62035.078.17 on 20-11-2017. Recruitment started on 30-1-2018.

Evaluation of effectiveness of the PlasmaJet surgical device in the treatment of advanced stage ovarian cancer (PlaComOv-study): study protocol of a randomized controlled trial in the Netherlands.

BACKGROUND: The most important goal for survival benefit of advanced stage ovarian cancer is to surgically remove all visible tumour, because complete cytoreductive surgery (CCS) has been shown to be associated with prolonged survival. In a remarkable number of women, CCS is very challenging. Especially in women with many small metastases on the peritoneum and intestinal surface, conventional CCS with electrosurgery is not able to be "complete" in removing safely all visible tumour. In this randomized controlled trail (RCT) we investigate whether the use of the PlasmaJet Surgical Device increases the rate of CCS, and whether this indeed leads to a longer progression free and overall survival. The main research question is: does the use of the PlasmaJet Surgical Device in surgery for advanced stage ovarian cancer result in an increased number of complete cytoreductive surgeries when compared with conventional surgical techniques. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. METHODS: The study design is a multicentre single-blinded superiority RCT in two university and nine non-university hospitals in The Netherlands. Three hundred and thirty women undergoing cytoreductive surgery for advanced stage ovarian carcinoma (FIGO Stage IIIB-IV) will be randomized into two arms: use of the PlasmaJet (intervention group) versus the use of standard surgical instruments combined with electrocoagulation (control group). The primary outcome is the rate of complete cytoreductive surgery in both groups. Secondary study objectives are: 30-day morbidity, duration of surgery, blood loss, length of hospitalisation, Quality of Life, disease-free survival, overall survival, percentage colostomy, cost-effectiveness. Quality of life will be evaluated using validated questionnaires at baseline, at 1 and 6 months after surgery and at 1, 2, 3 and 4 years after surgery. DISCUSSION: We hypothesize the additional value of the use of the PlasmaJet in CCS for advanced stage epithelial ovarian cancer. More knowledge about efficacy, side effects, recurrence rates, cost effectiveness and pathology findings after using the PlasmaJet Device is advocated. This RCT may aid in this void. TRIAL REGISTRATION: Dutch Trial Register NTR6624 . Registered 18 August 2017. Medical Ethical Committee approval number: NL62035.078.17 (Medical Ethical Committee Erasmus Medical Centre Rotterdam).

Measurement of the neutrino mass splitting and flavor mixing by MINOS.

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10(20) protons on target. A fit to neutrino oscillations yields values of |Δm(2)|=(2.32(-0.08)(+0.12))×10(-3) eV(2) for the atmospheric mass splitting and sin(2)(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively.

Active to sterile neutrino mixing limits from neutral-current interactions in MINOS.

Results are reported from a search for active to sterile neutrino oscillations in the MINOS long-baseline experiment, based on the observation of neutral-current neutrino interactions, from an exposure to the NuMI neutrino beam of 7.07×10(20) protons on target. A total of 802 neutral-current event candidates is observed in the Far Detector, compared to an expected number of 754 ± 28(stat) ± 37(syst) for oscillations among three active flavors. The fraction f(s) of disappearing ν(µ) that may transition to ν(s) is found to be less than 22% at the 90% C.L.

First direct observation of muon antineutrino disappearance.

This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν(µ) production, accumulating an exposure of 1.71 × 10²° protons on target. In the Far Detector, 97 charged current ν(µ) events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm²| = [3.36(-0.40)(+0.46)(stat) ± 0.06(syst)] × 10⁻³ eV², sin²(2θ) = 0.86(-0.12)(+0.11)(stat) ± 0.01(syst). The MINOS ν(µ) and ν(µ) measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters.

Improved search for Muon-neutrino to electron-neutrino oscillations in MINOS.

We report the results of a search for ν(e) appearance in a ν(µ) beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2 × 10(20) protons on the NuMI target at Fermilab, we find that 2 sin(2) (θ(23))sin(2)(2θ(13))<0.12(0.20) at 90% confidence level for δ = 0 and the normal (inverted) neutrino mass hierarchy, with a best-fit of 2sin(2) (θ(23))sin(2)(2θ(13)) = 0.041(-0.031)(+0.047) (0.079(-0.053) (+0.071)). The θ(13) = 0 hypothesis is disfavored by the MINOS data at the 89% confidence level.

Search for Lorentz invariance and CPT violation with the MINOS far detector.

We searched for a sidereal modulation in the MINOS far detector neutrino rate. Such a signal would be a consequence of Lorentz and CPT violation as described by the standard-model extension framework. It also would be the first detection of a perturbative effect to conventional neutrino mass oscillations. We found no evidence for this sidereal signature, and the upper limits placed on the magnitudes of the Lorentz and CPT violating coefficients describing the theory are an improvement by factors of 20-510 over the current best limits found by using the MINOS near detector.

Search for muon-neutrino to electron-neutrino transitions in MINOS.

This Letter reports on a search for nu(mu) --> nu(e) transitions by the MINOS experiment based on a 3.14x10(20) protons-on-target exposure in the Fermilab NuMI beam. We observe 35 events in the Far Detector with a background of 27+/-5(stat)+/-2(syst) events predicted by the measurements in the Near Detector. If interpreted in terms of nu(mu) --> nu(e) oscillations, this 1.5sigma excess of events is consistent with sin2(2theta(13)) comparable to the CHOOZ limit when |Delta m2|=2.43x10(-3) eV2 and sin2(2theta(23))=1.0 are assumed.

Can intravenous conscious sedation with midazolam be effective at facilitating surgical dentistry in adolescent orthodontic patients? A service evaluation.

Background Surgical dentistry during orthodontic care often occurs in adolescence and may involve surgical removal or exposure of teeth. The invasive nature of treatment, combined with dental anxiety, means care can often be provided under general anaesthesia (GA). Best-practice guidelines however endorse conscious sedation as an alternative, where appropriate. Although a limited number of studies have shown safe and effective use of intravenous conscious sedation (IVCS) with midazolam in this cohort, robust evidence to support routine use is lacking. Aim To assess whether IVCS with midazolam can effectively facilitate surgical dentistry in adolescent orthodontic patients in primary care.Method A retrospective service evaluation was undertaken reviewing clinical records of adolescents (aged 12-15 years) undergoing surgical exposure and/or surgical removal of teeth under IVCS with midazolam.Results A total of 174 adolescents (mean age 14.2 years) attended for treatment between 2009 and 2015. Of these adolescents, 98.9% (N = 172) allowed cannulation, with all surgical dentistry completed during a single visit. Midazolam dose ranged from 2-7 mg with 79.1% of patients having good or excellent cooperation and three minor adverse events occurring.Conclusion This service evaluation shows IVCS with midazolam can effectively facilitate surgical orthodontics in carefully selected adolescents. There is however a distinct need to further explore potential for this technique to provide a viable alternative to GA.

Distribution of neurofilament antigens after axonal injury.

Phosphorylated and nonphosphorylated epitopes of neurofilament (NF) proteins are distributed in different regions of individual neurons. Immunocytochemical methods, with monoclonal antibodies directed against phosphorylated and nonphosphorylated NF, demonstrated nonphosphorylated NF in perikarya and proximal axonal segments of neurons in dorsal root ganglia, while phosphorylated NF proteins were present in axons of these cells. The distribution of these epitopes of NF were examined at various times following injury of axons in the rat sciatic nerve. Between one and 21 days after crush of the proximal nerve, phosphorylated NF were present in neuronal perikarya. We have compared patterns of perikaryal immunoreactivity at one time point (three weeks) following a more distal crush or complete transection of the sciatic nerve. At this time period, following transection/ligation, phosphorylated NF immunoreactivity was not present in perikarya, but abnormal staining was observed after nerve crush. These altered distributions of phosphorylated epitopes of NF are of interest because several recent reports have indicated that similar, but not identical, abnormal staining patterns occur in human neurological diseases, including Alzheimer's disease and Parkinson's disease. In accord with previous studies, this investigation indicates that one response of neurons to injury, or to disease, is an abnormal distribution of phosphorylated epitopes of NF proteins.

Coronary bypass grafting in the elderly. Single versus bilateral internal mammary artery grafts.

A surgical experience between October 1983 and December 1990, with 1467 consecutive patients 65 years of age and over, was used to compare patients receiving single internal mammary artery grafts (n = 736) with those receiving bilateral internal mammary artery grafts (n = 731). The mean age in the single-graft group was 73.2 years and 70.9 years in the bilateral-graft group (p < 0.001). Various clinical parameters were analyzed that revealed that the single-graft group had more women and more patients with unstable angina, a history of previous myocardial infarction, and emergency surgery (p < 0.05). There was no significant difference in cigarette smoking, hypertension, diabetes mellitus, hyperlipidemia, triple vessel coronary artery disease, left main coronary artery stenosis, or left ventricular function between the two groups. Hospital mortality for the single-graft group was 6.4% (47 patients) and 3.1% (23 patients) for the bilateral-graft group (p < 0.004). No significant difference was observed between the groups in the rate of reoperation for bleeding, sternal infection, respiratory failure, stroke, or perioperative infarction. Follow-up was obtained in 663 hospital survivors (96.4%) in the single-graft group and in 691 (97.7%) in the bilateral-graft group. Mean follow-up in the single-graft group was 42.5 months (range, 1 to 92.4 months) and 43.0 months (range, 1 to 90.3 months) in the bilateral-graft group. In the single-graft group, survival was 60.7% +/- 4.8% (+/- standard error of the mean) at 8 years (60 patients at risk); it was 67.9% +/- 8.1% (18 patients at risk) for the bilateral-graft group (p < 0.028). This comparative study demonstrates that bilateral internal mammary artery grafting can be accomplished in elderly patients with low operative risk and hospital morbidity. Moreover, patients in both groups had a reduction in cardiac events and significant functional improvement.

Morphology of pig retinal pigment epithelium maintained in organ culture.

Exoplants of porcine retinal pigment epithelium (RPE) attached to Bruch's membrane, choroid, and sclera were maintained in organ culture for up to four weeks. Four-millimeter round buttons of eye wall that contained RPE, choroid, and sclera were trephined from freshly enucleated pig eyes and incubated at 37 degrees C in Eagle's minimum essential medium with 10% fetal calf serum. The RPE cells remained as a monolayer for at least four weeks in organ culture, and individual RPE cells became taller and dome shaped. The RPE cells retained several prominent ultrastructural features, including apical microvilli, intracellular melanosomes and mitochondria, and intercellular tight junctions. Since the cellular substratum can exert important influences on cell behavior, the ability to maintain RPE cells attached to Bruch's membrane provides a new in vitro tool for studying the metabolic activity of this tissue and its response to external stimuli, including laser photocoagulation.

Structural proteins of the neonatal and adult lamina cribrosa.

Optic nerve heads from three premature infants and six adults were studied immunohistochemically to compare the extracellular proteins in the lamina cribrosa of young and old human eyes. In both age groups, antibodies to the basement membrane components laminin and collagen type IV were associated with blood vessels and laminar beam margins. In the adult eyes, interstitial collagen types I and III were heavily distributed within the laminar beams. Antibodies to fibrillin, the microfibrillar portion of elastin, labeled discrete, heavy bands oriented longitudinally within these beams. The beams of the neonatal lamina cribrosa contained much less interstitial collagen, with a predominance of collagen type III. Neonatal elastic tissue bands were less numerous and distinct within the laminar beams. These biochemical differences between the young and old lamina cribrosa may, in part, explain different clinical behaviors of the optic nerve head in congenital and adult glaucoma.

Bilateral internal mammary artery grafting in women: a 21-year experience.

BACKGROUND: Coronary artery bypass grafting traditionally has carried a higher mortality rate in women than in men. It remains the leading cause of death in women despite major advances in diagnosis and treatment over the past 2 decades. METHODS: A retrospective analysis was conducted to identify risk factors that adversely influence hospital mortality, morbidity, and long-term clinical results in women undergoing bilateral internal mammary artery grafting. From January 1972 through October 1994, 327 consecutive women received bilateral internal mammary artery grafts and supplemental vein grafts. Patient age ranged from 32 to 84 years (mean, 65.7 years). There were 262 patients (80.1%) with three-vessel disease; 71 (21.7%) had substantial (> 50%) stenosis of the left main coronary artery, 65 (19.9%) had a moderately reduced (0.30 to 0.50) ejection fraction, and 11 (3.4%) had a severely reduced (< 0.30) ejection fraction. Preoperatively, 316 patients (96.6%) were in New York Heart Association class III or IV. RESULTS: There were 1,016 coronary artery grafts (mean, 3.1 per patient). The overall hospital mortality rate was 3.4% (11 of 327). Postoperative complications included myocardial infarction in 18 patients (5.5%), stroke in 5 (1.5%), pulmonary insufficiency in 11 (3.4%), reoperation for bleeding in 7 (2.1%), and sternal infection in 8 (2.4%). Independent predictors of operative death were postoperative cardiac arrest (p < 0.001), use of intraaortic balloon pump (p < 0.001), and reoperation for bleeding (p < 0.050). Follow-up was completed on 316 hospital survivors (100%) and ranged from 6 months to 21 years (mean, 5.1 years). Actuarial survival (mean +/- standard error of the mean) was 90.5% +/- 1.9% at 5 years and 65.6% +/- 6.1% at 10 years. At follow-up, 252 patients (94.0%) were asymptomatic in New York Heart Association class I, and 12 (4.5%) were in class II. CONCLUSIONS: This longitudinal study demonstrates that bilateral internal mammary artery grafting, though technically demanding, can be achieved in women with low hospital mortality and morbidity rates. Patients experienced reduced late cardiac events, excellent functional improvement, and enhanced long-term survival.

Twelve-year experience with bilateral internal mammary artery grafts.

A 12 1/2-year experience with 227 patients who underwent coronary revascularization with bilateral internal mammary artery (IMA) and supplemental saphenous vein grafts is presented. There were 725 coronary grafts performed (3.2 per patient). Forty-four IMA grafts were sequential. In 42 patients, the right IMA was placed through the transverse sinus to revascularize the circumflex artery. Operative mortality was 4% (9 of 227 patients). Postoperative complications included sternal infection (4 patients), reexploration for bleeding (5), and diaphragmatic dysfunction (10). Postoperative arteriography in 30 patients (mean interval, 4 1/4 years) revealed that 92% (34/37) of the left IMA and 87% (26/30) of the right IMA grafts were patent. Late follow-up was complete in 207 surviving patients. Eighteen late deaths (9 cardiac and 9 noncardiac) occurred. Actuarial survival was 83% at 10 years after operation. Of 68 patients followed from 8 to 12 1/2 years (mean interval, 10 1/2 years), 69% were asymptomatic, and 28% were in New York Heart Association Functional Class II. We conclude that bilateral IMA grafting can be accomplished with low operative risk and provides excellent long-term results.

Bilateral internal mammary artery grafts in reoperative and primary coronary bypass surgery.

Bilateral internal mammary artery grafting is recognized as a preferred method of myocardial revascularization. However, its efficacy in coronary bypass reoperation has not been clearly established. From January 1982 through June 1989, 88 patients underwent coronary bypass reoperation with bilateral internal mammary artery grafts. Results were compared with those for a subset of 88 patients receiving primary revascularization with bilateral internal mammary artery grafts who were computer matched for sex, age, left ventricular function, anginal classification, and left main coronary artery disease. In each group, 62.5% (55 patients) had unstable angina, 43.2% (38 patients) had reduced ejection fraction, and 21.6% (19 patients) in the reoperation group and 20.5% (18 patients) in the reference group had left main coronary artery disease. Hospital mortality for the reoperation group was 6.8% (6 patients) and for the reference group, 3.4% (3 patients). No significant difference was found in the incidence of reoperation for bleeding, sternal infection, or stroke in the two groups. The incidence of respiratory insufficiency in the reoperation group was 13.6% (12 patients) and in the reference group, 3.4% (3 patients) (p less than 0.015). Recurrent angina occurred in 13.7% (10 patients) of patients in the reoperation group and 13.3% (10 patients) in the reference group. The long-term survival at 5 years for the reoperation group was 85.3% +/- 5.6% (+/- standard error of the mean) and for the reference group, 91.6% +/- 3.1%. No significant difference was found in the equality of survival distribution for the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Seventeen-year experience with bilateral internal mammary artery grafts.

The internal mammary artery (IMA) is being recognized as the conduit of choice for myocardial revascularization. From January 1972 through June 1988, 1,087 patients received bilateral IMA and supplemental vein grafts. There were 917 men (84.4%) and 170 women (15.6%) with a mean age of 62.4 years (range, 29 to 84 years). Three hundred ninety-four patients (36.2%) had unstable angina, and 194 (17.8%) had left main coronary artery stenosis greater than 50%. In all, 3,741 coronary grafts were performed, with a mean of 3.4 per patient. Hospital mortality was 2.7% (29 patients). Hospital complications included reoperation for bleeding, 19 patients (1.7%); sternal infection, 16 patients (1.5%); respiratory failure, 35 patients (3.2%); perioperative myocardial infarction, 22 patients (2.0%); and stroke, 20 patients (1.8%). Post-operative arteriography in 53 patients (mean postoperative time, 53.0 months) showed that 92.1% (58/63) of the left IMA and 84.9% (45/53) of the right IMA grafts were patent. Follow-up was completed on 1,058 hospital survivors. There were 82 late deaths (7.8%). The actuarial survival for patients discharged from the hospital was 80.0 +/- 3.2% (plus or minus standard error of the mean) at 10 years and 60.0% +/- 5.0% at 15 years. At follow-up, 866 patients (90.3%) were asymptomatic and in New York Heart Association class I and 68 (7.1%) were in class II. This longitudinal analysis demonstrates that bilateral IMA grafting has a low operative risk and provides excellent long-term functional improvement and survival.

Hemispheric lateralization for speech perception in stutterers.

Sixteen adult, right-handed, moderate-to-severe atutterers (12 males, 4 females) and 20 nonstuttering controls (10 males, 10 females) were given a dichotic nonsense-syllable test to determine hemispheric lateralization for speech. Both male and female stutterers evidenced right-ear advantages in syllable identification similar in magnitude to those found for normals. These data confirm other reports of no difference in cerebral speech lateralization for stutterers and nonstutterers and, therefore, lend no support to theories that relate stuttering to abnormalities in cerebral lateralization. Acknowledgments. This study was conducted while the authors were at the University of Connecticut, Storrs. The assistance of Dr. R. L. Webster, the staff of the Institute for Behavioral Research, and the Departments of Psychology and Linguistics at the University of Connecticut is gratefully acknowledged.

Hemispheric specialization for speech perception in four-year-old children from low and middle socio-economic classes.

Four-year-old male and female children from low and middle socio-economic class (SEC) were presented a dichotic syllable task. Both low and middle SEC males evidenced significant right-ear advantages. Neither low nor middle SEC females evidenced a significant right-ear advantage. The similar ear advantage in the low and middle SEC populations replicates a previous study with six-year-olds and suggests that the variations in rearing conditions which occur in low and middle SEC classes does not affect hemispheric lateralization for speech perception.

Perception of temporal order in vowel sequences with and without formant transitions.

Temporal-order perception of phoneme segments in running speech is much superior to temporal-order perception in repeating vowel sequences. The more rapid rates possible in running speech may be due largely to the presence of formant transitions. In a series of five experiments we observed that many temporal-order misjudgements of repeating vowels can be explained in terms of auditory stream segregation, triggered for the most part by discontinuities in first-formant frequencies of adjacent vowels. Streaming, however, can be suppressed by formant transitions appropriate for the perception of stop consonants and by continuous transitions resembling those in coarticulated vowels. At rapid sequence rates, when the constraints of auditory streaming are removed, correct temporal-order identification is limited by linguistic transformations of vowels into other phoneme segments.