Real-world effectiveness and safety of stereotactic body radiotherapy for liver metastases with different respiratory motion management techniques.

PURPOSE: Stereotactic body radiotherapy (SBRT) has been firmly established as a treatment choice for patients with oligometastases, as it has demonstrated both safety and efficacy by consistently achieving high rates of local control. Moreover, it offers potential survival benefits for carefully selected patients in real-world clinical settings. METHODS: Between January 2008 and May 2020, a total of 149 patients (with 414 liver metastases) received treatment. The Active Breathing Coordinator device was used for 68 patients, while respiratory gating was used for 65 and abdominal compression was used for 16 patients. The most common histological finding was colorectal adenocarcinoma, with 37.6% of patients having three or more metastases, and 18% having two metastases. The prescribed dose ranged from 36 to 60 Gy, delivered in 3-5 fractions. RESULTS: Local control rates at 2 and 3 years were 76.1% and 61.2%, respectively, with no instances of local recurrence after 3 years. Factors negatively impacting local control included colorectal histology, lower prescribed dose, and the occurrence of new liver metastases. The median overall survival from SBRT was 32 months, with the presence of metastases outside the liver and the development of new liver metastases after SBRT affecting survival. The median disease-free survival was 10 months. No substantial differences in both local control and survival were observed between the respiratory motion control techniques employed. Treatment tolerance was excellent, with only one patient experiencing acute grade IV thrombocytopenia and two patients suffering from ≥ grade II chronic toxicity. CONCLUSION: For radical management of single or multiple liver metastases, SBRT is an effective and well-tolerated treatment option. Regardless of the technology employed, experienced physicians can achieve similarly positive outcomes. However, additional studies are required to elucidate prognostic factors that can facilitate improved patient selection.

Therapeutic Epigenetic Reprogramming of Trained Immunity in Myeloid Cells.

Infiltrating and tissue-resident myeloid cells are essential regulators of innate and adaptive immunity. During inflammation, and in response to microbial products, these cells can adapt to microenvironmental conditions and acquire specialized functions, including phagocytosis and the production of proinflammatory cytokines. Such myeloid plasticity is driven, in part, by epigenetic dynamics that can sustain stable phenotypes after activation, and which may lead to maladaptive cell polarization states associated with inflammation and autoimmunity. Here, we review recent reports describing epigenetic mechanisms linked to such polarization states and innate immune memory (tolerance and training) in monocyte and macrophage lineages. We discuss how these mechanisms might be targeted to develop putative immunomodulatory tools that might be used to treat a variety of immune-mediated diseases.

Influence of root width and dentin wall thickness evaluated by endoscopy upon the outcome of periapical surgery. A cohort study.

BACKGROUND: An analysis was made of the correlation between root width, the thickness of the remaining dentinal wall as determined by endoscopy, and the outcome of periapical surgery. MATERIAL AND METHODS: A retrospective cohort study was carried out involving patients subjected to periapical surgery between 2017 and 2019 at the University of Valencia (Valencia, Spain). One year after surgery, cone-beam computed tomography (CBCT) was used to evaluate healing against the preoperative volumes. The maximum root width was measured on the postoperative CBCT scan at the apical section of the treated root. This measurement was transferred to the intraoperative endoscopic image, where the minimum root width, peripheral dentin thickness, and minimum dentin thickness were recorded. Root measurements, and the position (maxillary or mandibular) and type of tooth (roots of incisors, canines, premolars or molars) were further correlated to periapical surgery outcome. RESULTS: A total of 51 patients, comprising 52 teeth and 62 roots, were included in the study. The mean measurements were: maximum root width (4.13±0.84 mm), minimum root width (2.46±0.72 mm), peripheral dentin thickness (0.77±0.2 mm) and minimum dentin thickness (0.4±0.2 mm). The success rate was 82.2%. Premolar roots showed a greater minimum dentin thickness (0.58±0.25 mm) (p<0.003) than incisor roots. No significant association was found between the different measurements and the healing rate at one year, though the roots that failed to heal showed smaller minimum dentin thickness values than the roots that healed correctly. The position and type of tooth did not influence healing outcome. CONCLUSIONS: The root width and thickness of the remaining dentin wall did not significantly influence healing. However, the roots that failed to heal showed smaller minimum dentin thickness values than the roots that healed correctly.

Endoscopic findings in periapical surgery. A cross-sectional study of 206 roots.

BACKGROUND: A study is made of the findings of high-magnification rigid endoscopy at the root end surface following apicoectomy of teeth subjected to periapical surgery. MATERIAL AND METHODS: A cross-sectional study was made of patients subjected to periapical surgery at the Unit of Oral Surgery and Implantology (University of Valencia, Valencia, Spain) between 2011 and 2019. Following apicoectomy, the root end surfaces were inspected, with the evaluation of untreated canals, isthmuses, craze lines, crack lines, opaque dentin and gaps. Likewise, an analysis was made of the association between patient age and the tooth type and restoration and the presence of craze lines, cracks, opaque dentin and gaps. RESULTS: The final sample consisted of 168 patients subjected to periapical surgery, with 177 operated teeth and 206 roots. Untreated canals were observed in 14 roots (6.8%). Isthmuses were identified in 74 roots (35.9%), particularly in the mesial root of the lower first molar (94.1%). In turn, craze lines were identified in 8.3% of the roots, cracks in 3.9%, and gaps in 53.4%. The prevalence of opaque dentin was 78.3%, with a greater presence in posterior teeth (90.3% in premolars and 86.2% in molars) than in anterior teeth (50.6%) (p<0.001). Patient age and tooth restoration showed no correlation to the studied parameters. CONCLUSIONS: Craze lines and crack lines were observed in less than 10% of the roots, though opaque dentin was identified in 73% of the roots, particularly in posterior teeth, and gaps were found in over half of the canals.

The type VI secretion system of Xanthomonas phaseoli pv. manihotis is involved in virulence and in vitro motility.

BACKGROUND: The type VI protein secretion system (T6SS) is important in diverse cellular processes in Gram-negative bacteria, including interactions with other bacteria and with eukaryotic hosts. In this study we analyze the evolution of the T6SS in the genus Xanthomonas and evaluate its importance of the T6SS for virulence and in vitro motility in Xanthomonas phaseoli pv. manihotis (Xpm), the causal agent of bacterial blight in cassava (Manihot esculenta). We delineate the organization of the T6SS gene clusters in Xanthomonas and then characterize proteins of this secretion system in Xpm strain CIO151. RESULTS: We describe the presence of three different clusters in the genus Xanthomonas that vary in their organization and degree of synteny between species. Using a gene knockout strategy, we also found that vgrG and hcp are required for maximal aggressiveness of Xpm on cassava plants while clpV is important for both motility and maximal aggressiveness. CONCLUSION: We characterized the T6SS in 15 different strains in Xanthomonas and our phylogenetic analyses suggest that the T6SS might have been acquired by a very ancient event of horizontal gene transfer and maintained through evolution, hinting at their importance for the adaptation of Xanthomonas to their hosts. Finally, we demonstrated that the T6SS of Xpm is functional, and significantly contributes to virulence and motility. This is the first experimental study that demonstrates the role of the T6SS in the Xpm-cassava interaction and the T6SS organization in the genus Xanthomonas.

Is periapical surgery follow-up with only two-dimensional radiographs reliable? A retrospective cohort type sensitivity study.

BACKGROUND: Two-dimensional (2D) radiographic techniques are commonly used for assessing lesion prognosis after endodontic surgery. The present retrospective cohort study analyzes the sensitivity and ability of different radiographic techniques in obtaining area and volume measurements of periapical lesions. MATERIAL AND METHODS: Preoperative and follow-up (6-48 months) periapical and panoramic radiographs (index test) and cone-beam computed tomography (CBCT) images (reference standard) were selected from an endodontic microsurgery database. Sensitivity was analyzed independently by two examiners. The areas of the 2D radiographic images and CBCT volumes were studied using Itk-Snap software and Romexis viewer. RESULTS: The sample comprised 105 patients and 105 teeth, with a mean follow-up of 21 months (range 6-48). Preoperatively, CBCT detected all the periapical areas, periapical radiography detected 67, and panoramic radiography detected 60. Postoperatively, of the 52 cases in which CBCT detected remains of the periapical area, periapical radiography detected 22, and panoramic radiography detected 17. The measurements of the areas obtained by the 2D methods, and the volumes obtained by CBCT, had to be transformed into linear measures for comparison purposes. The measurements were found to be significantly different in both the preoperative and the follow-up images. CONCLUSIONS:  Periapical radiography showed greater sensitivity than panoramic radiography, both preoperatively and at follow-up. The lesions measured with CBCT were larger, with significant differences than as evidenced by the periapical and panoramic radiographs.

Retroperitoneal soft-tissue sarcomas: Radiotherapy experience from a tertiary cancer center and review of current evidence.

BACKGROUND: Surgery remains to be the main therapeutic approach for retroperitoneal sarcomas (RPS) although evidence supports that complementary radiotherapy increases local-control and survival. We present a multidisciplinary management and experience of a tertiary cancer center in the treatment of RPS and analyze current evidence of radiotherapy efficacy. PATIENTS AND METHODS: We retrospectively reviewed 19 patients with primary or relapsed RPS treated between November 2009 and October 2018. Multidisciplinary approach comprised complete resection in 15 patients (79%) achieving resection R0 in 11 patients (58%), R1 in 4 patients (21%) and R2 in 2 patients (10%). Seven patients (37%) underwent a preoperative radiation (PRORT), 10 patients (53%), post-operative radiation (PORT) and 2 patients (10%), received radiotherapy exclusively. Ten patients (53%) received adjuvant chemotherapy. RESULTS: With a median follow-up of 24 months (2-114 months), actuarial rates of loco-regional relapse free survival (LRFS) at 1, 2 and 3 years were 77%, 77% and 67%, respectively. Actuarial rates of distant-metastases-free survival (DMFS), disease-free survival (DFS) and overall survival (OS) at 1, 2 and 3 years were 100%, 100% and 80% for DMFS; 94%, 77% and 67% for DFS and 100%, 91% and 91% for OS, respectively. Only surgical margins (negative vs. positive) showed significance for 3y-LRFS: 100% vs. 34.3%, p = 0.018. Treatment tolerance was acceptable with no acute or late toxicity higher than grade 2. CONCLUSIONS: Complementary radiotherapy appears to be useful and well tolerated for the multidisciplinary management of RPS. Presence of positive surgical margins seems to be the most relevant prognostic factor through the follow-up.

BET Proteins: An Approach to Future Therapies in Transplantation.

In order to develop new efficient therapies for organ transplantation, it is essential to acquire a comprehensive knowledge of the molecular mechanisms and processes, such as immune activation, chronic inflammation, and fibrosis, which lead to rejection and long-term graft loss. Recent efforts have shed some light on the epigenetic regulation associated with these processes. In this context, the bromo and extraterminal (BET) family of bromodomain proteins (BRD2, BRD3, BRD4, and BRDT) have emerged as major epigenetic players, connecting chromatin structure with gene expression changes. These proteins recognize acetylated lysines in histones and master transcription factors to recruit regulatory complex and, finally, modify the transcriptional program. Recent studies indicate that BET proteins are essential in the NF-kB-mediated inflammatory response, during the activation and differentiation of Th17-immune cells, and in profibrotic processes. Here, we review this new body of data and highlight the efficiency of BET inhibitors in several models of diseases. The promising results obtained from these preclinical models indicate that it may be time to translate these outcomes to the transplantation field, where epigenetics will be of increasing value in the coming years.

Plasma levels of trastuzumab in gastric cancer: Case report.

Introduction The use of trastuzumab with a fluoropyrimidine and platinum compound is currently the standard first-line treatment of patients with metastatic HER2-positive gastric cancer, but it appears that serum levels of trastuzumab determine the clinical effectiveness of this treatment, affecting progression-free survival and overall survival. Case report We report the case of a patient with metastatic HER2-positivegastric cancer, receiving XELOX (fluoropyrimidine and oxaliplatin) plus trastuzumab at standard doses, who presented sub-therapeutic serum levels during the first two treatment cycles and rapid disease progression (progression-free survival = 5.6 months). Discussion This case reveals a possible cause of poor effectiveness of trastuzumab treatment for metastatic gastric cancer in some patients, namely low circulating levels of the drug. It highlights the importance of monitoring as a possible tool for individual dose adjustment to optimize this therapy.

Diagnosis of endolymphatic hydrops by means of 3T magnetic resonance imaging after intratympanic administration of gadolinium. / Diagnóstico del hidrops endolinfático mediante resonancia magnética de 3T tras administración de gadolinio intratimpánico.

OBJECTIVE: To detect and graduate endolymphatic hydrops or endolymphatic space dilations in patients with suspected Meniere's disease or immune-mediated inner ear disease by magnetic resonance imaging. MATERIAL AND METHODS: A prospective study was performed including all the patients with clinical suspicion of Meniere's disease or immune-mediated inner ear disease treated at the Otolaryngology department during a one year period. In all cases, magnetic resonance imaging (MRI) was performed in a 3T scanner. IR sequence was performed after 24 to 28h prior intratimpanic injection of gadolinium on both ears. Two neurorradiologist graduated endolymphatic space volume as agreed on normal, moderate and significant in the obtained images. RESULTS: The presence of hydrops was documented by MRI in six patients with definite or probable Meniere's disease. In two of the four cases without vertigo hydrops was not demonstrated. In the other two cases with a high clinical suspicion of immune-mediated disease but with negative autoimmune tests hydrops was proved. There was only disagreement on cochlear hydrops presence on two patients. CONCLUSION: The detection of endolymphatic hydrops in patients with definite or probable Meniere's disease served to confirm the final diagnosis. Moreover, hydrops was detected in patients with suspected immune-mediated inner ear disease, which could have an impact on the diagnosis and treatment of these patients. Therefore, we suggest that this test could be included for the diagnosis of these inner ear diseases.

Nontraumatic head and neck injuries: a clinical approach. Part 2. / Urgencias no traumáticas de cabeza y cuello: aproximación desde la clínica. Parte 2.

Nontraumatic emergencies of the head and neck represent a challenge in the field of neuroradiology for two reasons. As explained in the first part of this update, these entities affect an area where the thorax joins the cranial cavity and can thus compromise both structures; second, they are uncommon, so they are not well known. Maintaining the same approach as in the first part, focusing on the clinical presentations in the emergency department rather than on the anatomic regions affected, we will study the entities that present with two patterns: those that present with a combination of cervical numbness, dysphagia, and dyspnea and those that present with acute sensory deficits. In the latter group, we will specifically focus on visual deficits, because this is the most common symptom that calls for urgent imaging studies.

Nontraumatic head and neck emergencies: a clinical approach. Part 1: cervicofacial swelling, dysphagia, and dyspnea. / Urgencias no traumáticas de cabeza y cuello. Aproximación desde la clínica. Parte 1: tumefacción cervicofacial, disfagia y disnea.

Nontraumatic emergencies of the head and neck represent a challenge in the field of neuroradiology for two reasons: first, they affect an area where the thorax joins the cranial cavity and can thus compromise both structures; second, they are uncommon, so they are not well known. Various publications focus on nontraumatic emergencies of the head and neck from the viewpoints of anatomic location or of particular diseases. However, these are not the most helpful viewpoints for dealing with patients in the emergency department, who present with particular signs and symptoms. We propose an analysis starting from the four most common clinical presentations of patients who come to the emergency department for nontraumatic head and neck emergencies: cervical swelling, dysphagia, dyspnea, and loss of vision. Starting from these entities, we develop an approach to the radiologic management and diagnosis of these patients.

Methylation of NKG2D ligands contributes to immune system evasion in acute myeloid leukemia.

Engagement of the activating receptor NKG2D (natural killer group 2 member D) with its ligands (NKG2DL) major histocompatibility complex class I related-A and -B (MICA/B), UL-16 binding protein families (ULBPs 1-6) is important to ensure the innate immunity to tumor cells. However, these cells have developed strategies to downregulate NKG2DL expression and avoid immune recognition. We demonstrate that DNA methylation can contribute to the absence of NKG2DL expression during tumor progression. We analyzed the DNA methylation profiles for each NKG2DL by pyrosequencing in acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), hepatocellular carcinoma (HC), breast cancer and colon cancer cell lines. High levels of DNA methylation for NKG2DL were found in some tumor cell lines, mainly in AML cells. This hypermethylation was correlated with the absence of transcription for NKG2DL. Higher DNA methylation levels for MICA, ULBP1 and ULBP2 were observed in AML patients (n=60) compared with healthy donors (n=25). However, no DNA methylation for NKG2DL was found in colon cancer patients (n=44). Treatment with demethylating agents (5-azacytidine and 5-aza-2'-deoxycytidine) restored the expression of NKG2DL on the cell surface of AML cells, leading to an enhanced recognition by NKG2D-expressing cells. Our data suggest that NKG2DL may be aberrantly silenced by DNA methylation as a consequence of tumor development in AML patients.

Real world comparison of the MGuard Stent versus the bare metal stent for ST elevation myocardial infarction (the REWARD-MI study).

AIM: The MGuard Stent (MGS) was designed to prevent distal embolization of thrombus and has been shown to improve microcirculation in ST-elevation myocardial infarction (STEMI). However, there are no real world data comparing it with the bare metal stent (BMS). The aim of this study is to determine the efficacy and safety of the MGS in STEMI in the real world compared to the BMS. METHODS AND RESULTS: In total, 262 patients were included from a single centre, of which 35.9% had an MGS implanted. Two groups of 79 patients were established after propensity score matching, and they were similar in terms of baseline and periprocedural variables. The mean follow-up was 321 ± 12.94 days. There was no difference in mortality (7.6% in both groups), major adverse cardiac events (20.3% vs. 12.7%, P = 0.198), non-cardiac mortality, or non-fatal myocardial infarction (6.3% in both groups). Target lesion revascularization (TLR) was significantly higher in the MGS group (11.4% (9) vs. 1.3% (1) P < 0.01; RR 10.02 [1.23-81.16]). CONCLUSION: Our study is the first to compare the MGS with the BMS in STEMI in the real world, and it also appears to confirm that although the MGS is a safe device in STEMI that is not associated with increased mortality, it is associated with a higher long-term TLR rate. © 2014 Wiley Periodicals, Inc.

Dispersion assessment in the location of facial landmarks on photographs.

The morphological assessment of facial features using photographs has played an important role in forensic anthropology. The analysis of anthropometric landmarks for determining facial dimensions and angles has been considered in diverse forensic areas. Hence, the quantification of the error associated to the location of facial landmarks seems to be necessary when photographs become a key element of the forensic procedure. In this work, we statistically evaluate the inter- and intra-observer dispersions related to the facial landmark identification on photographs. In the inter-observer experiment, a set of 18 facial landmarks was provided to 39 operators. They were requested to mark only those that they could precisely place on 10 photographs with different poses (frontal, oblique, and lateral views). The frequency of landmark location was studied together with their dispersion. Regarding the intra-observer evaluation, three participants identified 13 facial points on five photographs classified in the frontal and oblique views. Each landmark location was repeated five times at intervals of at least 24 h. The frequency results reveal that glabella, nasion, subnasale, labiale superius, and pogonion obtained the highest location frequency in the three image categories. On the contrary, the lowest rate corresponds to labiale inferius and menton. Meanwhile, zygia, gonia, and gnathion were significantly more difficult to locate than other facial landmarks. They produced a significant effect on the dispersion depending on the pose of the image where they were placed, regardless of the type of observer that positioned them. In particular, zygia and gonia presented a statistically greater variation in the three image poses, while the location of gnathion is less precise in oblique view photographs. Hence, our findings suggest that the latter landmarks tend to be highly variable when determining their exact position.

Ground truth data generation for skull-face overlay.

Objective and unbiased validation studies over a significant number of cases are required to get a more solid picture on craniofacial superimposition reliability. It will not be possible to compare the performance of existing and upcoming methods for craniofacial superimposition without a common forensic database available for the research community. Skull-face overlay is a key task within craniofacial superimposition that has a direct influence on the subsequent task devoted to evaluate the skull-face relationships. In this work, we present the procedure to create for the first time such a dataset. We have also created a database with 19 skull-face overlay cases for which we are trying to overcome legal issues that allow us to make it public. The quantitative analysis made in the segmentation and registration stages, together with the visual assessment of the 19 face-to-face overlays, allows us to conclude that the results can be considered as a gold standard. With such a ground truth dataset, a new horizon is opened for the development of new automatic methods whose performance could be now objectively measured and compared against previous and future proposals. Additionally, other uses are expected to be explored to better understand the visual evaluation process of craniofacial relationships in craniofacial identification. It could be very useful also as a starting point for further studies on the prediction of the resulting facial morphology after corrective or reconstructive interventionism in maxillofacial surgery.

Molecular and phenotypic characterization of Agrobacterium species from vineyards allows identification of typical Agrobacterium vitis and atypical biovar 1 strains.

AIM: To molecularly and phenotypically characterize a selection of Agrobacterium-like isolates from grapevine canes, crowns, soil and tumours in plants grown under cold conditions. METHODS AND RESULTS: Most of the strains were biovar 3 (Agrobacterium vitis), and the remaining were atypical biovar 1 (Agrobacterium tumefaciens). All of them were tumourigenic on grapevine plants but differences in other hosts were observed. Chromosomal and plasmid-borne traits were analysed by gene amplification with four primer sets. Detection of the pectin enzyme hydrolase gene clearly distinguished A. vitis from the atypical A. tumefaciens. Regarding the virulence sensor gene, limited host range tumour-inducing plasmids were found in the atypical isolates. About opine utilization, most A. vitis and some A. tumefaciens contained octopine/cucumopine plasmids, but the nopaline-type was only detected in one A. tumefaciens. CONCLUSIONS: The A. vitis strains were molecularly and phenotypically more homogeneous than those of A. tumefaciens, the latter displaying some typical A. vitis characteristics, suggesting an adaptation to life in grapevine. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this work will help to improve detection procedures of the pathogen, and demonstrate the pathogen diversity in cold vineyards, laying the groundwork for epidemiological studies and development of control strategies of the crown and cane gall disease.

Asymptomatic carotid stenosis and cognitive improvement using transcervical stenting with protective flow reversal technique.

OBJECTIVES: The relationship between carotid artery stenosis and cognitive function in individuals without a history of stroke is not clear. The possible pathomechanisms of cognitive impairment include silent embolization and hypoperfusion. In this study the aim was to assess cognitive changes after transcervical carotid artery stenting with proximal cerebral protection by flow reversal in patients with asymptomatic carotid stenosis, a novel technique that has been proved to decrease the number intraoperative emboli. METHODS: 25 consecutive patients were assessed, of which 22 were men (88%) mean age of 74 years with severe asymptomatic carotid stenosis who underwent revascularization by carotid artery stenting (CAS) with flow reversal. Patients were evaluated 1 day before and 6 months after the procedure using a standardized neuropsychological battery. Test scores were adjusted according to age, sex, education level and were standardized (0-100). The mean of all the cognitive function scores yielded the global cognitive score (GCS). RESULTS: There were no neurological complications during the procedure or during hospitalization in any patient. No deaths or cardiac complications occurred in any patient. The pre-procedure neuropsychological study showed cognitive impairment in: information processing speed in 15 patients (62.5%), visuospatial function in 14 (56.0%), memory in 18 (72.0%), executive functions in 14 (56.0%), language in three (12.0%), attention in 10 (40.0%), and global cognitive performance in eight (32.0%). Comparison of these scores with those obtained 6-month post-procedure showed significant improvement in GCS in all patients (p = .002), with a particularly marked gain in information processing speed (p = .018). Although significant improvement was not found for the remaining cognitive functions assessed, some gain was documented, and there was no deterioration. CONCLUSIONS: Revascularization by transcervical CAS with flow reversal for cerebral protection results in improved neurocognitive performance in asymptomatic elderly patients with severe carotid artery stenosis.

Perineural spread in head and neck tumors.

Perineural spread is the dissemination of some types of head and neck tumors along nervous structures. Perineural spread has negative repercussions on treatment because it requires more extensive resection and larger fields of irradiation. Moreover, perineural spread is associated with increased local recurrence, and it is considered an independent indicator of poor prognosis in the TNM classification for tumor staging. However, perineural spread often goes undetected on imaging studies. In this update, we review the concept of perineural spread, its pathogenesis, and the main pathways and connections among the facial nerves, which are essential to understand this process. Furthermore, we discuss the appropriate techniques for imaging studies, and we describe and illustrate the typical imaging signs that help identify perineural spread on CT and MRI. Finally, we discuss the differential diagnosis with other entities.