The prognostic role of epidermal growth factor receptor (EGFR) and HER2-neu remains controversial in patients with non-small
cell lung cancer (NSCLC). We studied the association between the mRNA ...expression of EGFR, HER2-neu, and survival in primary
tumor and matching nonmalignant tissues from 83 patients with NSCLC. Analysis was performed using a quantitative real-time
PCR system (Taqman). EGFR and HER2-neu mRNA expression was detectable in all (100%) specimens analyzed. Twenty-nine (34.9%)
patients had high HER2-neu expression, and 28 (33.7%) patients had high EGFR expression. A high HER2-neu and EGFR coexpression
was detectable in 14 (16.9%) patients. High HER2-neu expression was associated with inferior survival ( P = 0.004), whereas high EGFR expression showed a trend toward inferior survival ( P = 0.176). The impact of HER2-neu and EGFR coexpression on patients’ survival was additive ( P = 0.003). Multivariate analysis determined high HER2-neu expression ( P = 0.041), and high EGFR/HER2-neu coexpression ( P = 0.030) as significant and independent unfavorable prognostic factors. These findings indicate that HER2-neu and EGFR play
a crucial role in the biological behavior of NSCLCs. Testing of molecular marker coexpression (EGFR and HER2-neu) improves
the estimation of prognosis and appears to define low- and high-risk groups for treatment failure in curatively resected NSCLC.
A considerable percentage of morbidity and mortality after esophagectomy and gastric pull-up is due to leakage of the esophagogastrostomy, which is mainly caused by ischemia of the gastric fundus. ...Previous clinical studies demonstrated that impaired microcirculation of the gastric conduit almost recovers within the first 5 postoperative days. Therefore, this study was designed to improve gastric perfusion by laparoscopic ischemic conditioning of the stomach.
The study group consisted of 83 patients with 44 esophageal adenocarcinomas and 39 squamous cell carcinomas. A total of 51% received neoadjuvant radiochemotherapy. First, all patients underwent laparoscopic mobilization of the stomach including the cardia and preparation of the gastric conduit. After a mean delay of 4.3 days (range, 3-7 days), a conventional right-sided transthoracic en bloc esophagectomy was performed. Reconstruction was done by gastric pull-up and high intrathoracic esophagogastrostomy.
Three conversions (3.6%) to open surgery were necessary during laparoscopic mobilization of the stomach. The reoperation rate was 2.4% (one relaparoscopy for control of a bleeding of the stapler line, one rethoracotomy for chylothorax). Two patients showed circumscribed necroses of the upper part of the fundus after gastric pull-up into the chest. These necroses were resected for reconstruction by esophagogastrostomy. Five patients (6.0%) developed small anastomotic leakages with minor clinical symptoms; however, the gastric conduits were well vascularized. All leakages healed after endoscopic stenting. Major postoperative complications were observed in 13.3% of the patients and the 90-day mortality was 0%.
Laparoscopic ischemic conditioning of the gastric conduit is feasible and safe and may contribute to the reduction of postoperative morbidity and mortality after esophagectomy and gastric pull-up.
The evolution of surgical approach for esophageal cancer Gisbertz, Suzanne S.; Hagens, Eliza R.C.; Ruurda, Jelle P. ...
Annals of the New York Academy of Sciences,
December 2018, 2018-Dec, 2018-12-00, 20181201, Volume:
1434, Issue:
1
Journal Article
Peer reviewed
Open access
Esophageal surgery for esophageal cancer has been performed for over a century now. Minimally invasive esophagectomy (MIE) was first described in 1992, and it is now a standard approach in many ...countries. However, MIE is technically difficult and requires a long learning curve. It takes >100 cases to train for MIE with gastric tube reconstruction with an intrathoracic anastomosis. A possible option to overcome several challenges of MIE might be the use of a robotic system. A robot‐assisted MIE was first described in 2005, and long‐term results have shown its feasibility and safety. Over the years, different approaches for esophagectomy have been established. Our review discusses these developments and recent literature on open, minimally invasive and robotic esophageal surgery.
Minimally invasive esophagectomy (MIE) is technically difficult and requires a long learning curve. A possible option to overcome several challenges of MIE might be the use of a robotic system. A robot‐assisted MIE was first described in 2005, and long‐term results have shown its feasibility and safety. Our review discusses these developments and recent literature on open, minimally invasive and robotic esophageal surgery.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The aims of this study were to evaluate, using 3-dimensional superimposition techniques, the skeletal changes in Class II subjects with different vertical facial patterns treated with the Herbst ...appliance and to compare these skeletal changes to those of Class II controls treated with elastics.
Sixteen Herbst patients who met the inclusion criteria were divided into 2 equal groups based on vertical facial pattern as determined by the Frankfort mandibular plane angle (brachyfacial, ≤22°; mesofacial, 23°-29°) and had cone-beam computed tomographs taken before treatment, 8 weeks after Herbst appliance removal, and after subsequent fixed appliance treatment. Eleven Class II control patients treated with fixed appliances and elastics had cone-beam computed tomographs taken before and after treatment. Three-dimensional models were generated from the cone-beam computed tomography images, registered on the anterior cranial bases, and analyzed using color maps and point-to-point measurements.
There were minimal differences in treatment response between the 2 Herbst groups across all skeletal parameters measured. The Herbst subjects showed a greater inferior displacement of anterior nasal spine compared with the Class II controls (Herbst brachyfacial, −1.44 mm; Herbst mesofacial, −1.95 mm) with other maxillary changes being clinically insignificant. The Herbst subjects showed greater inferior displacement of B-point compared with the Class II controls (Herbst brachyfacial, −2.59 mm; Herbst mesofacial, −2.75 mm). There were no statistically significant differences in mean linear mandibular measurements. All groups showed a trend toward posterior displacement of the condyles and glenoid fossae from the start to the end of treatment, with no significant differences across the 3 groups. There were minimal differences in the changes in gonial angle and Frankfort mandibular plane angle across all groups.
Approximately 2 years after Herbst treatment, the Herbst subjects with different vertical facial patterns showed similar patterns of skeletal change compared with the Class II controls treated with elastics.
•Three-dimensional data allow accurate evaluation of skeletal changes with the Herbst appliance.•Differences in vertical facial pattern are proposed to modify treatment response.•Minimal differences in maxillary change were found in the Herbst groups vs the control.•Minimal differences in fossa remodeling were found in the Herbst groups vs the control.•Minimal differences in mandibular change were found in the Herbst groups vs the control.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
We sought to quantitatively and objectively evaluate histomorphologic tumor regression and establish a relevant prognostic regression classification system for esophageal cancer patients receiving ...neoadjuvant radiochemotherapy.
Eighty-five consecutive patients with localized esophageal cancers (cT2-4, Nx, M0) received standardized neoadjuvant radiochemotherapy (cisplatin, 5-fluorouracil, 36 Gy). Seventy-four (87%) patients were resected by transthoracic en bloc esophagectomy and 2-field lymphadenectomy. The entire tumor beds of the resected specimens were evaluated histomorphologically, and regression was categorized into grades I to IV based on the percentage of vital residual tumor cells (VRTCs). A major response was achieved when specimens contained either less than 10% VRTCs (grade III) or a pathologic complete remission (grade IV).
Complete resections (R0) were performed in 66 of 74 (89%) patients with 3-year survival rates of 54% +/- 7.05% for R0-resected cases and 0% for patients with incomplete resections or tumor progression during neoadjuvant therapy (P < 0.01). Minor histopathologic response was present in 44 (59.5%) and major histopathologic response in 30 (40.5%) tumors. Significantly different 3-year survival rates (38.8% +/- 8.1% for minor versus 70.7 +/- 10.1% for major response) were observed. Univariate survival analysis identified histomorphologic tumor regression (P < 0.004) and lymph node category (P < 0.01) as significant prognostic factors. Pathologic T category (P < 0.08), histologic type (P = 0.15), or grading (P = 0.33) had no significant impact on survival. Cox regression analysis identified dichotomized regression grades (minor and major histomorphologic regression, P < 0.028) and lymph node status (ypN0 and ypN1, P < 0.036) as significant independent prognostic parameters. A 2-parameter regression classification system that includes histomorphologic regression (major versus minor) and nodal status (ypN0 versus ypN1) was established (P < 0.001).
Histomorphologic tumor regression and lymph node status (ypN) were significant prognostic parameters for patients with complete resections (R0) following neoadjuvant radiochemotherapy for esophageal cancer. A regression classification based on 2 parameters could lead to improved objective evaluation of the effectiveness of treatment protocols, accuracy of staging and restaging modalities, and molecular response prediction.
Alterations in the blood brain barrier and brain vasculature may be involved in neurodegeneration and neuroinflammation. We sought to determine if vascular remodeling characterized by angiogenic ...vessels or increased vascular density, occurred in pathologically confirmed Alzheimer’s disease (AD) postmortem human brain tissues. We examined brains of deceased, older catholic clergy from the Religious Order Study, a longitudinal clinical–pathological study of aging and AD. The hippocampus, midfrontal cortex, substantia nigra, globus pallidus and locus ceruleus were examined for integrin αvβ3 immunoreactivity, a marker of angiogenesis, and vascular densities. Activated microglia cell counts were also performed. All areas except the globus pallidus exhibited elevated αvβ3 immunoreactivity in AD cases compared with controls. Only in the hippocampus did the ongoing angiogenesis result in increased vascular density compared with controls. Vascular density was correlated with Aβ load in the hippocampus and αvβ3 reactivity was correlated with neurofibrillary tangles in the midfrontal cortex and in the substantia nigra. These data indicate that ongoing angiogenesis is present in brain regions affected by AD pathology and may be related to tissue injury.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca
2+
release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased ...metabolic demand. Mitochondria from female hearts exhibit lower mito-Ca
2+
and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca
2+
accumulation, thereby reducing ROS production and stress-induced intracellular Ca
2+
mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-Ca
2+
in female rat VCMs challenged with β-adrenergic agonist isoproterenol compared to males. Biochemical studies revealed decreased mitochondria Ca
2+
uniporter expression and increased supercomplex assembly in rat and human female ventricular tissues vs male. Importantly, western blot analysis showed higher expression levels of COX7RP, an estrogen-dependent supercomplex assembly factor in female heart tissues vs males. Furthermore, COX7RP was decreased in hearts from aged and ovariectomized female rats. COX7RP overexpression in male VCMs increased mitochondrial supercomplexes, reduced mito-ROS and spontaneous SR Ca
2+
release in response to ISO. Conversely, shRNA-mediated knockdown of COX7RP in female VCMs reduced supercomplexes and increased mito-ROS, promoting intracellular Ca
2+
mishandling. Compared to males, mitochondria in female VCMs exhibit higher ETC subunit incorporation into supercomplexes, supporting more efficient electron transport. Such organization coupled to lower levels of mito-Ca
2+
limits mito-ROS under stress conditions and lowers propensity to pro-arrhythmic spontaneous SR Ca
2+
release. We conclude that sexual dimorphism in mito-Ca
2+
handling and ETC organization may contribute to cardioprotection in healthy premenopausal females.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
IMPORTANCE No national standardized guidelines exist to date for venous thromboembolism (VTE) prophylaxis after pediatric trauma. While the risk of VTE after trauma is generally lower for children ...than for adults, the precise age at which the risk of VTE increases is not clear. OBJECTIVE To identify the age at which the risk of VTE after trauma increases from the low rate seen in children toward the higher rate seen in adults. DESIGN, SETTING, AND PARTICIPANTS Multivariable logistic regression models were used to estimate the association between age and the odds of VTE when adjusting for other VTE risk factors. Participants included 402 329 patients 21 years or younger who were admitted following traumatic injury between January 1, 2008, and December 31, 2010, at US trauma centers participating in the National Trauma Data Bank. MAIN OUTCOMES AND MEASURES Diagnosis of VTE as a complication during hospital admission. RESULTS Venous thromboembolism was diagnosed in 1655 patients (0.4%). Those having VTE were more severely injured compared with those not having VTE and more frequently required critical care, blood transfusion, central line placement, mechanical ventilation, and surgery. The risk of VTE was low among younger patients, occurring in 0.1% of patients 12 years or younger, but increased to 0.3% in patients aged 13 to 15 years and to 0.8% in patients 16 years or older. These findings remained when adjusting for other factors, with patients aged 13 to 15 years (adjusted odds ratio, 1.96, 95% CI 1.53-2.52; P < .001) and patients aged 16 to 21 years (adjusted odds ratio, 3.77; 95% CI, 3.00-4.75; P < .001) having a significantly higher odds of being diagnosed as having VTE compared with patients aged 0 to 12 years. These findings were consistent across the level of injury severity and the type of trauma center. CONCLUSIONS AND RELEVANCE The risk of VTE varies considerably across patient age and increases most dramatically at age 16 years, after a smaller increase at age 13 years. These findings can be used to guide future research into the development of standardized guidelines for VTE prophylaxis after pediatric trauma.
Methods of antibody detection are used to assess exposure or immunity to a pathogen. Here, we present Ig-MS, a novel serological readout that captures the immunoglobulin (Ig) repertoire at molecular ...resolution, including entire variable regions in Ig light and heavy chains. Ig-MS uses recent advances in protein mass spectrometry (MS) for multiparametric readout of antibodies, with new metrics like Ion Titer (IT) and Degree of Clonality (DoC) capturing the heterogeneity and relative abundance of individual clones without sequencing of B cells. We applied Ig-MS to plasma from subjects with severe and mild COVID-19 and immunized subjects after two vaccine doses, using the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 as the bait for antibody capture. Importantly, we report a new data type for human serology, that could use other antigens of interest to gauge immune responses to vaccination, pathogens, or autoimmune disorders.
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IJS, KILJ, NUK, PNG, UL, UM
Quantitative analysis of enamel on debonded orthodontic brackets Cochrane, Nathan J.; Lo, Thomas W.G.; Adams, Geoffrey G. ...
American journal of orthodontics and dentofacial orthopedics,
September 2017, 2017-Sep, 2017-09-00, 20170901, Volume:
152, Issue:
3
Journal Article
Peer reviewed
Iatrogenic damage to the tooth surface in the form of enamel tearouts can occur during removal of fixed orthodontic appliances. The aim of this study was to assess debonded metal and ceramic brackets ...attached with a variety of bonding materials to determine how frequently this type of damage occurs.
Eighty-one patients close to finishing fixed orthodontic treatment were recruited. They had metal brackets bonded with composite resin and a 2-step etch-and-bond technique or ceramic brackets bonded with composite resin and a 2-step etch-and- bond technique, and composite resin with a self-etching primer or resin-modified glass ionomer cement. Debonded brackets were examined by backscattered scanning electron microscopy with energy dispersive x-ray spectroscopy to determine the presence and area of enamel on the base pad.
Of the 486 brackets collected, 26.1% exhibited enamel on the bonding material on the bracket base pad. The incidences of enamel tearouts for each group were metal brackets, 13.3%; ceramic brackets, 30.2%; composite resin with self-etching primer, 38.2%; and resin-modified glass ionomer cement, 21.2%. The percentage of the bracket base pad covered in enamel was highly variable, ranging from 0% to 46.1%.
Enamel damage regularly occurred during the debonding process with the degree of damage being highly variable. Damage occurred more frequently when ceramic brackets were used (31.9%) compared with metal brackets (13.3%). Removal of ceramic brackets bonded with resin-modified glass ionomer cement resulted in less damage compared with the resin bonding systems.
•Enamel damage was more frequent with ceramic bracket removal than metal brackets.•Damage was less when ceramic brackets were attached with RMGIC than composite resin.•Ceramic bracket fracture was greatest with 2-step etch-and-bond composite resin.•The most common bond failure site was the bracket-bonding material interface.•Maxillary lateral incisors had a greater risk of damage than central incisors and canines.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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