The Histopathological Growth Pattern of Colorectal Liver Metastases Impacts Local Recurrence Risk and the Adequate Width of the Surgical Margin.

BACKGROUND: The histopathological growth pattern (HGP) of colorectal liver metastases (CLM) has been associated with prognosis. This study was designed to elucidate if the HGP is associated with local recurrence risk and impacts the adequate width of surgical margin. METHODS: All consecutive patients resected for CLM in 2018-2019 were considered. HGP was prospectively classified as follows: desmoplastic, pushing, and replacement. Surgical margin was classified as follows: R0 (margin ≥ 1 mm), R1vasc (0-mm margin, tumor detachment from intrahepatic vessels), and R1par (tumor exposure along transection plane). R0 resections were further distinguished in R0min (1-mm margin) and R0wide (> 1-mm margin). RESULTS: A total of 340 resection areas in 136 patients were analyzed (70 R0min, 143 R0wide, 31 R1vasc, 96 R1par). HGP was desmoplastic in 26 cases, pushing in 221, and replacement in 93. Thirty-six local recurrences occurred (11%, median follow-up 21 months): 1 after R0wide, 4 after R0min, 3 after R1vasc, and 28 after R1par resection. In R1par group, local recurrence rate was high independently of HGP (29%). In R1vasc and R0min groups, local recurrence risk was higher in the replacement group (R1vasc: 29% vs. 4% if pushing/desmoplastic; R0min: 11% vs. 4%). In R0wide group, local recurrence risk was low for all HGP ( < 1%). Independent predictors of local recurrence were replacement HGP (odds ratio = 1.654, P = 0.036), and R1par resection (odds ratio = 57.209, P < 0.001 vs. R0). CONCLUSIONS: Replacement HGP is associated with an increased risk of local recurrence. In these patients, a wide surgical margin should be pursued, because R1vasc and R0min resections could be insufficient. R1par resection is inadequate, independently of the HGP.

Comparative molecular analysis of bacterial species associated with periodontal disease.

Periodontal disease is an inflammatory disorder affecting the supporting teeth structures, including gingiva, periodontal ligament and alveolar bone, causing loss of connective tissue, reabsorption of alveolar bone and formation of periodontal pockets. The aim of this study is to find a correlation between bacterial growth and periodontal disease. Fifty-seven patients aged between 21 and 65 years, median age 46 years, were enrolled. According to gingival pocket depth, ranging from 3 to 7 mm, patients were divided into two groups: the first (30 patients, 53%) with deep pockets ³ 5 mm and the second (27 patients, 47%) less than 5 mm. The samples taken were processed for microbiological analysis by absolute quantitative real-time Taq-Man technique. Patients affected by periodontal disease were 32 (56%) and patients with gingival bleeding were 35 (61%). This data showed that the presence, the type and the bacterial load in gingival pockets were strongly correlated with gingival depth, periodontal disease and gingival bleeding. Quantitative microbiological analysis is a key point to improve patient compliance, allowing to choose the specific antibiotic treatment. avoiding antibiotic resistance and ensuring the successful outcome of therapy for periodontal disease.

Possible role of tocopherols in the modulation of host microRNA with potential antiviral activity in patients with hepatitis B virus-related persistent infection: a systematic review.

Hepatitis B virus (HBV) infection represents a serious global health problem and persistent HBV infection is associated with an increased risk of cirrhosis, hepatocellular carcinoma and liver failure. Recently, the study of the role of microRNA (miRNA) in the pathogenesis of HBV has gained considerable interest as well as new treatments against this pathogen have been approved. A few studies have investigated the antiviral activity of vitamin E (VE) in chronic HBV carriers. Herein, we review the possible role of tocopherols in the modulation of host miRNA with potential anti-HBV activity. A systematic research of the scientific literature was performed by searching the MEDLINE, Cochrane Library and EMBASE databases. The keywords used were 'HBV therapy', 'HBV treatment', 'VE antiviral effects', 'tocopherol antiviral activity', 'miRNA antiviral activity' and 'VE microRNA'. Reports describing the role of miRNA in the regulation of HBV life cycle, in vitro and in vivo available studies reporting the effects of VE on miRNA expression profiles and epigenetic networks, and clinical trials reporting the use of VE in patients with HBV-related chronic hepatitis were identified and examined. Based on the clinical results obtained in VE-treated chronic HBV carriers, we provide a reliable hypothesis for the possible role of this vitamin in the modulation of host miRNA profiles perturbed by this viral pathogen and in the regulation of some cellular miRNA with a suggested potential anti-HBV activity. This approach may contribute to the improvement of our understanding of pathogenetic mechanisms involved in HBV infection and increase the possibility of its management and treatment.

A new prognostic clinicopathological classification of pituitary adenomas: a multicentric case-control study of 410 patients with 8 years post-operative follow-up.

Pituitary adenomas are currently classified by histological, immunocytochemical and numerous ultrastructural characteristics lacking unequivocal prognostic correlations. We investigated the prognostic value of a new clinicopathological classification with grades based on invasion and proliferation. This retrospective multicentric case-control study comprised 410 patients who had surgery for a pituitary tumour with long-term follow-up. Using pituitary magnetic resonance imaging for diagnosis of cavernous or sphenoid sinus invasion, immunocytochemistry, markers of the cell cycle (Ki-67, mitoses) and p53, tumours were classified according to size (micro, macro and giant), type (PRL, GH, FSH/LH, ACTH and TSH) and grade (grade 1a: non-invasive, 1b: non-invasive and proliferative, 2a: invasive, 2b: invasive and proliferative, and 3: metastatic). The association between patient status at 8-year follow-up and age, sex, and classification was evaluated by two multivariate analyses assessing disease- or recurrence/progression-free status. At 8 years after surgery, 195 patients were disease-free (controls) and 215 patients were not (cases). In 125 of the cases the tumours had recurred or progressed. Analyses of disease-free and recurrence/progression-free status revealed the significant prognostic value (p < 0.001; p < 0.05) of age, tumour type, and grade across all tumour types and for each tumour type. Invasive and proliferative tumours (grade 2b) had a poor prognosis with an increased probability of tumour persistence or progression of 25- or 12-fold, respectively, as compared to non-invasive tumours (grade 1a). This new, easy to use clinicopathological classification of pituitary endocrine tumours has demonstrated its prognostic worth by strongly predicting the probability of post-operative complete remission or tumour progression and so could help clinicians choose the best post-operative therapy.

Systemic nickel allergy syndrome: nosologic framework and usefulness of diet regimen for diagnosis.

Systemic (gastrointestinal and skin) reactions to ingestion of nickel rich foods in patients with nickel allergic contact dermatitis characterize Systemic Nickel Allergy Syndrome (SNAS). The objective of the study was to describe the nosologic framework of the syndrome and to compare sensibility and specificity for SNAS diagnosis between two different low nickel diets - BraMa-Ni and the usually prescribed list of forbidden foods - along with patient adherence to diet. One hundred forty-five patients with suspected SNAS (by history and benefit from nickel dietary restrictions) were selected and orally challenged with nickel for a definite diagnosis. Specificity and sensibility of the diets were calculated in relation to the results of nickel challenges. The nosologic framework of SNAS was deduced from the clinical pictures of 98 patients with positive nickel challenge and characterized essentially by skin and gastrointestinal symptoms, whereas all other symptoms (dizziness, headache etc.) were never elicited by the oral nickel challenge. The specificity and sensibility of BraMa-Ni in detecting SNAS were significantly higher than the forbidden food list diet, with an excellent patient adherence. Therefore, BraMa-Ni diet can be prescribed for the treatment of the syndrome other than for the diagnosis, the gold standard of which remains the oral nickel challenge.

Impact of capsaicin on mast cell inflammation.

Mast cells are inflammatory cells, and they are prominent in inflammatory diseases such as allergy and asthma. Mast cells possess high-affinity receptors for IgE (FcERI) and the cross-linking of these receptors is essential to trigger the secretion of granules containing arachidonic acid metabolism (such as prostaglandin (PG) D2, leukotriene (LT) B4, and LTC4), histamine, cytokines, chemokines, and proteases, including mast cell-specific chymases and tryptases. Activation of mast cells provokes the secretion of cytokines and mediators that are responsible for the pathologic reaction of immediate hypersensitivity. Sensory nerve stimulation by irritants and other inflammatory mediators provokes the release of neuropeptides, causing an increase in vascular permeability, plasma extravasation and edema. Trigeminal nerve stimulation actives dura mast cells and increases vascular permeability, effects inhibited by capsaicin. Capsaicin causes release of sensory neuropeptide, catecholamines and vasodilation. Several studies have reported that capsaicin is effective in relief and prevention of migraine headaches, improves digestion, helps to prevent heart disease, and lowers blood cholesterol and blood pressure levels. The findings reported in these studies may have implications for the pathophysiology and possible therapy of neuroinflammatory disorders.

Clinical management of patients with thymic epithelial tumors: the recommendations endorsed by the Italian Association of Medical Oncology (AIOM).

The Italian Association of Medical Oncology recommendations on thymic epithelial tumors, which have been drawn up for the first time in 2020 through an evidence-based approach, report indications on all the main aspects of clinical management of this group of rare diseases, from diagnosis and staging, to new available systemic treatments, such as targeted therapies and immunotherapies. A summary of key recommendations is presented here and complete recommendations are reported as Supplementary Materials, available at https://doi.org/10.1016/j.esmoop.2021.100188.

Sinusal localization of nodal micrometastases is a prognostic factor in breast cancer.

BACKGROUND: Breast cancer micrometastases are frequently found during pathological examination of sentinel lymph nodes and complete axillary lymph node dissection. Despite this, their clinical relevance is still debated. The aim of this study is to investigate features that affect disease-free survival (DFS) and overall survival (OS) in patients with nodal micrometastases from breast cancer. MATERIAL AND METHODS: We retrospectively investigated the outcome of 122 patients with nodal micrometastases from breast cancer followed up for 60 months. RESULTS: At univariate analysis, worse DFS was related to features of primary tumor (multifocality P = 0.002; size >2 cm, P = 0.022; grade P = 0.022; absence of estrogen P < 0.001 and progesterone P < 0.001 receptors; HER-2 overexpression P = 0.006; vascular invasion P = 0.039; proliferative fraction > or =20% P = 0.034) and micrometastases (sinusal localization P = 0.010). Among the above-mentioned features, two were strongly associated with worse DFS in the multivariate model, i.e. negative receptorial status [hazard ratio (HR) = 11.24, 95% confidence interval (CI) 4.06-31.09; P < 0.001] and sinusal localization of micrometastasis (HR = 3.66, 1.18-11.36; P = 0.025). The OS was influenced by multifocality (P < 0.001) and receptor status (P = 0.005). CONCLUSION: Our results indicate that in patients affected by breast cancer, in addition to the well-known pathological features of primary tumor, sinusal localization of micrometastasis strongly impacts on the prognosis.

[About a simple method to prevent accidents caused by changes in positioning in surgery: The transparent head drape]. / Le champ de tête transparent. Un moyen simple de prévention des accidents liés au changement d'installation en chirurgie plastique.

Surgical drapes are a physical barrier between the surgical team's sterile working space (the operating field) and the non-sterile environment of the anaesthesia team and the nursing team within the operating theatre. Once the patient's position has been checked and the skin preparation has been done, they are put in place. They are usually opaque, leaving visible just the areas where the surgical and anaesthesia teams will be working. When the patient's position is changed perioperatively, malpositions may be unnoticed and cause complications. Using a transparent head drape allows one to check the position of the head and upper limbs at all times, thus reducing the risk of complications. It is a simple, easy, economic, non-restrictive method which will produce an improvement in the quality of patient care.

Primary resistance to cetuximab therapy in EGFR FISH-positive colorectal cancer patients.

The impact of KRAS mutations on cetuximab sensitivity in epidermal growth factor receptor fluorescence in situ hybridisation-positive (EGFR FISH+) metastatic colorectal cancer patients (mCRC) has not been previously investigated. In the present study, we analysed KRAS, BRAF, PI3KCA, MET, and IGF1R in 85 mCRC treated with cetuximab-based therapy in whom EGFR status was known. KRAS mutations (52.5%) negatively affected response only in EGFR FISH+ patients. EGFR FISH+/KRAS mutated had a significantly lower response rate (P=0.04) than EGFR FISH+/KRAS wild type patients. Four EGFR FISH+ patients with KRAS mutations responded to cetuximab therapy. BRAF was mutated in 5.0% of patients and none responded to the therapy. PI3KCA mutations (17.7%) were not associated to cetuximab sensitivity. Patients overexpressing IGF1R (74.3%) had significantly longer survival than patients with low IGF1R expression (P=0.006), with no difference in response rate. IGF1R gene amplification was not detected, and only two (2.6%) patients, both responders, had MET gene amplification. In conclusion, KRAS mutations are associated with cetuximab failure in EGFR FISH+ mCRC, even if it does not preclude response. The rarity of MET and IGF1R gene amplification suggests a marginal role in primary resistance. The potential prognostic implication of IGF1R expression merits further evaluation.

Combined endoscopic approach in the treatment of benign broncho-oesophageal fistula.

The treatment of benign broncho-oesophageal fistula is usually surgical but sometimes other methods of treatment are preferred. The case history is described of an adult in poor general condition in which an endoscopic approach combined with the use of fibrin glue on the bronchial side and metallic clips on the oesophageal side was used to close the fistula.

[18F]FDG-PET/CT texture analysis in thyroid incidentalomas: preliminary results.

BACKGROUND: significance of incidental thyroid 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) uptake on positron emission tomography/computed tomography (PET/CT) scans remains controversial. We aimed to evaluate the ability of [18F]FDG-PET/CT texture analysis to predict final diagnosis in thyroid incidentaloma. METHODS: We retrospectively evaluated medical records of all patients who performed a [18F]FDG-PET/CT from January 2012 to October 2016. Those patients who presented a thyroid incidentaloma described in the medical records and performed a fine needle aspiration in our institution were considered for the analysis. Cytological and/or histological results were used as reference standard to define the final diagnosis. In case of negative cytology, the nodule was considered benign. In case of non-diagnostic or inconclusive results ultrasound, follow-up and further cytology/histology were used as final diagnosis. For suspected or positive cytological result, histology was used as reference standard. PET images were segmented using a General Electric AW workstation running PET VCAR software (GE Healthcare, Waukesha, WI, USA) settled with a threshold of 40% SUVmax. LifeX software (http://www.lifexsoft.org) was used to perform texture analysis. Statistical analysis was performed with R package (https://www.r-project.org). RESULTS: We identified 55 patients with incidental thyroid [18F]FDG uptake. Five patients were excluded from the analysis because a final diagnosis was not available. Thirty-two out of 50 patients had benign nodules while in 18/50 cases a malignancy (primary thyroid cancer = 15, metastases = 3) was diagnosed. Conventional PET parameters and histogram-based features were calculated for all 50 patients, while other matrices-based features were available for 28/50 patients. SUVmax and skewness resulted significantly different in benign and malignant nodules (p = 0.01 and = 0.02, respectively). Using ROC analysis, seven features were identified as potential predictors. Among all the textural features tested, skewness showed the best area under the curve (= 0.66). SUV-based parameters resulted in the highest specificity while MTV, TLG, skewness and kurtosis, as well as correlationGLCM resulted better in sensitivity. CONCLUSIONS: [18F]FDG-PET/CT texture analysis seems to be a promising approach to stratify the patients with thyroid incidentaloma identified on PET scans, with respect to the risk of the diagnosis of a malignant thyroid nodule and thus, could refine the selection of the patients to be referred for cytology.

[A new human machine interface in neurosurgery: The Leap Motion(®). Technical note regarding a new touchless interface]. / Un nouvel interface homme machine en neurochirurgie : le Leap Motion(®). Note technique sur une nouvelle interface homme machine sans contact.

Currently, cross-sectional imaging viewing is used in routine practice whereas the surgical procedure requires physical contact with an interface (mouse or touch-sensitive screen). This type of contact results in a risk of lack of aseptic control and causes loss of time. The recent appearance of devices such as the Leap Motion(®) (Leap Motion society, San Francisco, USA) a sensor which enables to interact with the computer without any physical contact is of major interest in the field of surgery. However, its configuration and ergonomics produce key challenges in order to adapt to the practitioner's requirements, the imaging software as well as the surgical environment. This article aims to suggest an easy configuration of the Leap Motion(®) in neurosurgery on a PC for an optimized utilization with Carestream(®) Vue PACS v11.3.4 (Carestream Health, Inc., Rochester, USA) using a plug-in (to download at: https://drive.google.com/?usp=chrome_app#folders/0B_F4eBeBQc3ybElEeEhqME5DQkU) and a video tutorial (https://www.youtube.com/watch?v=yVPTgxg-SIk).

Progesterone receptor expression in orbital cavernous hemangiomas.

Orbital cavernous hemangiomas (OCH) have thick and highly cellular vascular walls. Ultrastructural studies have demonstrated the smooth muscle nature of these cells. Vascular neoplasms can modify their morphological and clinical features under hormonal stimulation. The purpose of the present study was to investigate the presence of smooth muscle markers and sex steroid receptors in 12 cases of OCH. Orbital cases were compared with cutaneous hemangiomas and subcutaneous angioleiomyomas. Smooth muscle actin (SMA) and desmin were localized in spindle cells of the vascular walls of all 12 cases studied. OCH showed immunohistochemical positivity with progesterone receptor (PR) antibody both in smooth muscular and in endothelial cells. For comparison, sex steroid receptors were studied in 10 cases of cutaneous cavernous hemangioma and in 10 cases of subcutaneous angioleiomyoma. PR was found in smooth muscle and endothelial cells of 6 out of 10 cases of subcutaneous angioleiomyoma and in none of the cases of cutaneous cavernous hemangioma. No positivity was obtained with estrogen receptor (ER) antibody in any of the cases tested. The present data suggest that OCH share morphological and immunohistochemical features with subcutaneous angioleiomyomas. Furthermore, immunohistochemical positivity with PR antibody indicates that OCH have to be added to the list of mesenchymal lesions that express sex steroid receptors.

Identification of mitochondria in liver biopsies. A study by immunohistochemistry, immunogold and Western blot analysis.

Hepatocytes are rich in mitochondria, which play an important role in hepatic metabolism. In certain pathologic conditions (most often alcoholic liver disease) mitochondria became enlarged; nevertheless, even in these conditions they are hardly detectable on light microscopy. Recently an antimitochondrial antibody (mAM), which recognizes a 60-kDa protein, has been characterized. The purpose of the present study was to study immunoreactivity of this antibody in a series of liver biopsies. We studied 146 liver biopsies using an mAM. In 8 cases an ultrastructural study was also done, and in 2 cases Western blot analysis was performed. Cases were divided as follows: alcoholic liver disease (ALD, 31); steatosis (8); nonalcoholic steatohepatitis (NASH, 1); hepatitis C virus (HCV)-related hepatitis (83); hepatitis B virus (HBV)-related hepatitis (6); primary biliary cirrhosis (1); sclerosing cholangitis (1); haemosiderosis (1); sarcoidosis (1); alpha-1-antitrypsin deficiency (1); nonspecific findings (12). All the patients were investigated for alcohol or drug abuse, pharmacological treatment, hyperlipidaemia, hypercholesterolaemia and diabetes. Immunoreactivity was diffuse in cases of ALD, NASH and steatosis, and in patients with drug abuse. Electron microscopic immunogold and Western blot analysis confirmed that in the conditions examined the protein recognized by the mAM showed greater expression. Immunohistochemical staining was helpful in demonstrating a toxic or a metabolic insult even in cases in which the histological picture was blurred by viral infection.

Correlation between histologic staging, hepatitis C virus genotypes and clinical features in HCV chronic hepatitis: evidence of a new pattern.

Genome heterogeneity may be related to the wide variability of clinical and pathological features in hepatitis C virus (HCV)-related chronic liver disease. This paper addresses the possible association between HCV subtypes and clinical and histological features of chronically infected patients. Sixty-eight consecutive liver biopsies of chronic hepatitis constituted the basis of the study. HCV genotyping was performed on frozen tissue. Grading of necroinflammatory activity and staging of fibrosis were histologically assessed. Serologic HCV-RNA and liver function were assessed at the same time. All information was compared with clinical data including age, sex, HCV serology, and probable data and route of infection. Two cases were excluded as inadequate tissue was available. Five cases were negative to HCV-RNA in both serum and tissue. In 61 cases HCV RNA was present at the same time in serum and liver tissue. Forty-four patients were men (72%) and 17 (28%) were women. Two peaks of age were observed: 1 in the 4th decade of life, the 2nd in the 7th. The 2 groups had different HCV genotypes. Patients with genotypes 1b (mean age 50.7 years), 2c (mean age 61.3 years), and a subgroup of coinfections (mean age 60 years) were older than patients with genotypes 1a (mean age 35.5 years), 3 (mean age 36 years), and a subgroup of coinfections (mean age 33 years). Patients with genotypes 1b, 2, or 2c and a subgroup of coinfections more frequently had a history of blood transfusion and or surgical intervention dating up to 49 years previously. Patients with HCV 1a, 3, and a subgroup of coinfections frequently admitted a period of intravenous drug abuse. Patients with advanced liver disease, i.e., severe fibrosis and cirrhosis, showed the same 2 peaks of incidence: in the 4th and 7th decades of life, the first group mainly comprising patients with HCV types 1a and 3, the second, patients with HCV types 1b and 2c. Both these groups shared a clinical history of a long-standing infection. Two profiles of patients emerged. The largest group was composed of elderly patients, infected by HCV genotypes 1b or 2c, with a history of blood transfusion and/or surgery, presenting an advanced stage of liver disease (namely, severe fibrosis or cirrhosis). The second group was composed of younger patients, mainly in the 4th decade of life, infected by HCV types 3 or 1a, often presenting with chronic hepatitis in the stage of severe fibrosis or cirrhosis. The latter could be the profile of HCV infection in the near future.

Bioprosthetic valve endocarditis: factors affecting bad outcome.

Prosthetic valve endocarditis (PVE) remains an uncommon but serious complication of cardiac valve replacement. We analysed several risk factors (active or healed, early or late endocarditis, congestive heart failure, arterial emboli etc.) in order to identify the factors which may predict bad outcome. The overall mortality rate was 46.8% (15/32 patients). There was a significantly higher mortality rate in patients with early endocarditis (80%) than in those with late endocarditis (38%) (p less than 0.01). In the group of patients who underwent reoperation, the mortality rate was higher in those with active endocarditis (70%) than in those with healed endocarditis (28.5%) (p less than 0.05). We believe that combined medical and surgical treatment is the best management for bioprosthetic valve endocarditis, with the institution of appropriate preoperative antibiotic therapy, to attempt to achieve sterilization.

Aortic valve replacement through a minimally invasive approach.

Minimally invasive cardiac surgery is rapidly gaining interest because of fast recovery, reduced morbidity, shorter hospital stay, lower costs, and better cosmetic results. Aortic valve surgery can be performed through a small (10- to 12-cm) transverse sternal incision, and femoro-femoral cannulation is used for cardiopulmonary bypass. Exposure of the ascending aorta is satisfactory. From 1 March through 30 September 1996, 7 patients underwent aortic valve replacement through this approach. The mean age of the 5 women and 2 men was 58.8 years. We used this technique mainly in patients with chronic obstructive pulmonary disease, diabetes, or obesity, in the absence of coronary artery disease. There was no mortality, nor was there reoperation for bleeding, stroke, or wound infection. All patients were extubated after 2 hours in intensive care and were discharged on the 4th postoperative day. Additional cases are needed to properly assess the correct indication and surgical technique.

Carotid endarterectomy and myocardial revascularization. A single stage procedure.

Carotid endarterectomy (CEA) and myocardial revascularization can be performed in a single procedure, performing CEA before or during cardio-pulmonary by-pass (CPB), or using a double stage approach. Over a 4 year period, 17 patients underwent CEA and coronary artery by-pass (CAB) with a single stage procedure. Fourteen patients (82.3%) were male, 3 (17.6%) were female. The mean age was 66.3 +/- 7.07. One patient (5.8%) had a previous neurological event (stroke); 5 patients (29.4%) had a previous transient ischemic attacks (TIA). The indications for the combined operations were CAD associated to unilateral internal carotid stenosis greater than 70% or 50% when symptomatic. In all patients CEA was performed after median sternotomy and heparinization, during CPB, with moderate hypotermia (30%C), performing CEA successively. One patient (5.8%) died of acute heart failure secondary to mediastinits. Minor neurological complications were present in 2 patients (11.7%) with signs of cerebral oedema. Myocardial infarction and late neurological deficit did not occur in any patient. We conclude that it is important, in the preoperative assessment of every patients with CAD, the screening for concomitant carotid vascular diseases, in order to avoid neurological complications during CPB, treating the two different diseases with a single stage approach, if carotid stenosis is greater than 70% or greater than 50% when symptomatic.