The Clinical Significance of MicroRNAs in Colorectal Cancer Signaling Pathways: A Review.

Colorectal carcinoma (colon and rectum) is currently considered among the most prevalent malignancies of Western societies. The pathogenesis and etiological mechanisms underlying colorectal cancer (CRC) development remain complex and heterogeneous. The homeostasis and function of normal human intestinal cells is highly regulated by microRNAs. Therefore, it is not surprising that mutations and inactivation of these molecules appear to be linked with progression of colorectal tumors. Recent studies have reported significant alterations of microRNA expression in adenomas and CRCs compared with adjacent normal tissues. This observed deviation has been proposed to correlate with the progression and survival of disease as well as with choice of optimal treatment and drug resistance. MicroRNAs can adopt either oncogenic or tumor-suppressive roles during regulation of pathways that drive carcinogenesis. Typically, oncogenic microRNAs termed oncomirs, target and silence endogenous tumor-suppressor genes. On the other hand, tumor-suppressive microRNAs are critical in downregulating genes associated with cell growth and malignant capabilities. By extensively evaluating robust studies, we have emphasized and distinguished a discrete set of microRNAs that can modulate tumor progression by silencing specific driver genes crucial in signaling pathways including Wnt/b-catenin, epidermal growth factor receptor, P53, mismatch repair DNA repair, and transforming-growth factor beta.

Bilateral palsy of the hypoglossal nerve following general anesthesia for emergency surgery. A case report.

INTRODUCTION AND IMPORTANCE: Hypoglossal nerve palsy is a rare condition usually associated with tumors, trauma, stroke or multiple sclerosis. It can be associated with other cranial nerve palsies while injury to this nerve typically affects a patient's articulation by causing lingual motility disturbance and swallowing difficulty. Bilateral isolated hypoglossal nerve palsy is an even more infrequent condition, which can occasionally be due to airway manipulation. CASE PRESENTATION: We describe a case of bilateral hypoglossal nerve damage following general anesthesia for emergency surgery, presenting with dysarthria, immobility of the tongue and dysphagia after extubation. The patient had a gradual recovery of all lost functions during the next four months. CLINICAL DISCUSSION: Bilateral hypoglossal nerve palsy is a very rare entity and tracheal tube malposition or prolonged but unnoticed tracheal cuff pressure especially in the face of low blood pressure, should be considered as possible causative mechanisms for this condition. This underlines the importance of careful positioning of the patient's head and neck during surgery as well as the meticulous and correct performance of routine maneuvers of airway management. CONCLUSION: Bilateral hypoglossal nerve palsy is a very rare entity. Diagnosis and management of twelfth nerve palsy require a multidisciplinary approach to achieve the best patient outcome.

Two-step treatment of a giant skull vault hemangioma: A rare case report and literature review.

Skull vault hemangiomas are benign vascular tumours of the calvaria that are usually asymptomatic or present as firm, painless lumps. We present a case of a 59-year-old female with a giant intraosseous calvarial hemangioma that was admitted in our department with a palpable mass over the left frontoparietal region, personality changes and impaired emotional and cognitive functions. The patient was treated with a two-step approach involving endovascular and surgical treatment, and suffered two rare, but recognized complications, a contrecoup intracerebral haemorrhage and valproate-induced stupor and parkinsonism. At the 6-month follow-up, the patient had complete recovery with a good neurological outcome.

Place of hyperthermic intraperitoneal chemotherapy in the armament against pancreatic adenocarcinoma: A survival, mortality and morbidity systematic review.

Pancreatic adenocarcinoma is one of the deadliest types of cancer worldwide, with a 5-year survival rate of 8% despite recent treatment advancements. The present systematic review aimed to investigate the role of hyperthermic intraperitoneal chemotherapy (HIPEC) following surgical resection for pancreatic adenocarcinoma, with or without peritoneal carcinomatosis. A systematic search of the MEDLINE and SCOPUS electronic databases was performed according to PRISMA guidelines. All possible relevant articles published between January 1980 and May 2019 were retrieved using multiple search terms associated with HIPEC and pancreatic adenocarcinoma. The initial search resulted in 1,244 reports, which condensed to 41 reports following screening of titles and abstracts, and subsequently to four reports following full-text thorough examination. The four reports included involved a prospective cohort study of HIPEC use in resectable pancreatic adenocarcinoma, and three retrospective studies of HIPEC use following cytoreductive surgery for peritoneal carcinomatosis due to pancreatic adenocarcinoma, resulting in a total of 47 patients. The overall survival ranged between 2 and 62 months, and the hospital mortality rate was 8.5%. Morbidity (34%) was mainly attributed to anastomotic leak or respiratory failure. Due to the small sample size and low quality of evidence of the included studies, no valid conclusions could be drawn. Therefore, further studies are required to justify the use of HIPEC as an adjuvant therapy in resectable pancreatic adenocarcinoma, while cytoreductive surgery and HIPEC in peritoneal carcinomatosis of pancreatic origin seems not only not useful but also unsafe at this level of evidence.

Two-step treatment of a giant skull vault hemangioma: A rare case report and literature review.

Skull vault hemangiomas are benign vascular tumours of the calvaria that are usually asymptomatic or present as firm, painless lumps. We present a case of a 59-year-old female with a giant intraosseous calvarial hemangioma that was admitted in our department with a palpable mass over the left frontoparietal region, personality changes and impaired emotional and cognitive functions. The patient was treated with a two-step approach involving endovascular and surgical treatment, and suffered two rare, but recognized complications, a contrecoup intracerebral haemorrhage and valproate-induced stupor and parkinsonism. At the 6-month follow-up, the patient had complete recovery with a good neurological outcome.

Jitter Remains Stable Throughout a Single Fiber EMG Session in Healthy and Myasthenic Muscles.

Fatigability is the hallmark of myasthenia gravis (MG). It is not clear, however, whether there is an analogous increase in jitter during the course of a single fiber electromyography (SFEMG) session. The individual jitter values of all potentials of 76 normal and 44 myasthenic orbicularis oculi muscles were assigned a rank number according to their temporal order in which they were collected and linear regression was performed to determine if the slope of the regression line was significantly different from zero. Control and MG subjects displayed rather flat linear regression lines with non-significant positive or negative slopes. Accordingly, ROC analysis yielded areas under the curve near 0.5. We conclude that there is no systematic jitter increase during the collection of 20 potential pairs in a typical SFEMG session.

Targeted prevention of road traffic deaths in Greece: a multifactorial 5-year census-based study.

BACKGROUND: Between 2012 and 2016, Greece suffered yearly more than 800 deaths from road traffic incidents (RTIs), holding one of the worst performances in the European Union for RTI-related deaths per population. Our primary aim is to identify risk factors associated with mortality to set a targeted policy framework on road safety. METHODS: This is a retrospective analysis of data collected prospectively from Traffic Police. A correlation of 29 factors with adult drivers' mortality was made, applying multivariate logistic regression models. At a second stage, a scoping literature review identified the best possible targeted prevention measures. RESULTS: A total of 93,019 drivers with a mean age of 42.2 ± 0.1 years were recorded, of which 2772 (3%) died. Age above 65 (aOR 3.1, p < 0.001), non-use of seatbelt (aOR 8.2, p < 0.001) or helmet (aOR 2.85, p < 0.001) and alcohol consumption (aOR 3.3 for cars, 4 for motorbikes, p < 0.001) were the driver-related parameters with the strongest correlation with a fatal outcome. Drivers' behavior with specific high-risk maneuvers increased odds of death 2-4 times, depending on vehicle type. One-lane, rural road network was the environmental factor with the most significant impact. Based on the results of the analyses, our scoping review identified and suggested 23 specific measures for the Greek government and policymakers to examine. CONCLUSION: Human-related factors were the parameters with the strongest impact on mortality after an RTI in Greece. These findings demonstrate an educational gap that must be primarily addressed with the introduction of missing road safety education in schools and an intensified and innovative population awareness campaign.

Identifying jitter outliers in single fiber electromyography: Comparison of four methods.

BACKGROUND: Little is known about how different outlier estimation methods affect cutoff limits for outliers in single fiber electromyography. METHODS: We compared in a prospective fashion the established 18th jitter value (18thjv) method to three, whole-distribution based, outlier detection methods: the interquartile range (IQR), the log-normal, and the Z-score method. The reference limits were probed in a normal cohort and in myasthenia gravis (MG) patients. RESULTS: Differences in outlier cutoff values between the different methods were in the range of 2 µs. The number of abnormal muscles according to the computed criteria was similar for all four methods in the control group. Classification metrics (sensitivity, specificity, Youden's statistic, and predictive values) were also similar among the different methods. In the MG group, however, the Z-score method failed to identify the abnormal jitter values. Accordingly, Kappa agreement was substantial to perfect (0.658 to 1) between the three methods (18thjv, IQR, and log-normal), but was equivalent to chance between the three methods and the Z-score in the MG group. CONCLUSIONS: The established 18thjv method proved largely robust when compared to whole-distribution based methods, and its use in clinical practice is justified. Simple estimation of outlier limits by adding two SDs to the mean of the data, leads to unacceptable deviations from the true cutoff values. Moreover, in a clinical scenario in which the final electrodiagnosis depends only on the number of outliers, it is meaningful to accept a tolerance zone of about 2 µs, which is the approximate variation range among the different methods.

Primary headache subtypes and thyroid dysfunction: Is there any association? / Subtipos de cefaleia primária e disfunção tireoidiana: existe alguma associação?

ABSTRACT Background: Primary headaches, and particularly migraine and tension-type headache (TTH) as well as hypothyroidism are common medical conditions. To date, numerous studies have suggested a possible bidirectional relationship between migraine and hypothyroidism, although certain studies had contradictory results. Objective: To investigate whether there is any association between primary headache subtypes and thyroid disorders. Methods: A retrospective study of consecutive patients aged ≥18 years referred to the Headache Outpatient Clinic of Aeginition Hospital and diagnosed with primary headache and any thyroid disorder. Results: Out of 427 patients (males/females=76/351), 253 (59.3%) were diagnosed with migraine without aura, 53 (12.4%) with TTH, 49 (11.5%) with migraine with aura, 29 (6.8%) with medication-overuse headache, 23 (5.4%) with mixed-type headache (migraine with/without aura and TTH), nine (2.1%) with cluster headache, and 11 (2.6%) with other types of primary headaches. The prevalence of any type of thyroid disorder was 20.8% (89/427 patients). In the total sample, 27 patients (6.3%) reported hypothyroidism, 18 (4.2%) unspecified thyroidopathy, 14 (3.3%) thyroid nodules, 12 (2.8%) Hashimoto thyroiditis, 12 (2.8%) thyroidectomy, three (0.7%) thyroid goiter, and three (0.7%) hyperthyroidism. Further statistical analysis between categorical variables did not reveal any significant association between headache subtypes and thyroid dysfunction. Conclusions: No specific association was found between primary headache subtypes and specific thyroid disorder. However, a high prevalence of thyroid dysfunction in general and specifically hypothyroidism was demonstrated among patients with primary headaches, which lays the foundation for further clarification in prospective longitudinal studies.

RESUMO Introdução: Cefaleias primárias e, particularmente, enxaqueca e cefaleia do tipo tensional (CTT), bem como hipotiroidismo, constituem condições médicas comuns. Até o momento, vários estudos sugeriram uma possível relação bidirecional entre enxaqueca e hipotireoidismo, embora alguns estudos tenham resultados contraditórios. Objetivo: Investigar se existe associação entre subtipos de cefaleia primária e distúrbios da tireoide. Métodos: Estudo retrospectivo de pacientes consecutivos com idade ≥18 anos encaminhados ao Ambulatório de Cefaleia do Hospital Aeginition, com diagnóstico de cefaleia primária e qualquer distúrbio da tireoide. Resultados: De 427 pacientes (homens/mulheres=76/351), 253 pacientes (59,3%) foram diagnosticados com enxaqueca sem aura, 53 (12,4%) com CTT, 49 (11,5%) com enxaqueca com aura, 29 (6,8 %) com cefaleia por uso excessivo de medicamentos, 23 (5,4%) com cefaleia mista (enxaqueca com/sem aura e CTT), nove (2,1%) com cefaleia em salvas e 11 (2,6%) com outros tipos de cefaleias primárias. A prevalência de qualquer tipo de distúrbio tireoidiano foi de 20,8% (89/427 pacientes). Na amostra total, 27 pacientes (6,3%) relataram hipotireoidismo, 18 (4,2%) tireoidopatia não especificada, 14 (3,3%) nódulos de tireoide, 12 (2,8%) tireoidite de Hashimoto, 12 (2,8%) tireoidectomia, três (0,7%) bócio da tireoide e três (0,7%) hipertireoidismo. Uma análise estatística posterior entre as variáveis categóricas não revelou qualquer associação significativa entre os subtipos de cefaleia e disfunção tireoidiana. Conclusões: Não encontramos associação entre subtipos de cefaleia primária e distúrbio específico da tireoide. No entanto, foi observada prevalência elevada de disfunção tireoidiana em geral e especificamente hipotireoidismo entre pacientes com cefaleia primária, o que estabelece base para maiores esclarecimentos em estudos longitudinais prospectivos.

Salivary inflammatory markers in tension type headache and migraine: the SalHead cohort study.

OBJECTIVE: To investigate the possible association between salivary CRP, IL-1ß, and IL-6 levels, depression/anxiety and migraine, and tension type headache (TTH) in saliva of these patients. METHOD: A longitudinal prospective study was conducted on 30 migraineurs, 30 TTH patients, and 30 age-matched healthy controls. Anxiety and depression were measured by using the Hamilton Anxiety Rating Scale (HAM-A), and the Beck Depression Inventory (BDI). Salivary IL-6, IL-1ß, and CRP were collected in distinct time points as A: headache-free period, B: during headache, C: 1 day after headache attack, and measured by using ELISA kits. RESULTS: No significant differences were found in time variation of CRP, IL-1ß, and IL-6 levels between migraine and TTH (p > 0.05). IL1-ß had the highest discriminative value (area under the curve = 0.924, p value < 0.001), and then CRP (area under the curve = 0.763, p value < 0.001) and IL-6 (area under the curve = 0.537, p value = 0.58). CRP and IL-6 were negatively correlated with HAM-A and BDI scores. CONCLUSION: IL1-ß had the highest discriminative value between headache patients and controls compared with CRP and IL-6. CRP and IL-6 were correlated with lower symptom scores of anxiety and depression prior or immediately after the headache period in patients groups.

Ocular flutter as presenting manifestation of pediatric MOG antibody-associated demyelination: A case report.

A 13-year-old girl presented with a 5-day history of oscillopsia. On examination, ocular flutter and mild cerebellar signs were found. Brain magnetic resonance imaging (MRI) revealed four periventricular and subcortical non-enhancing lesions. Cerebrospinal fluid (CSF) oligoclonal bands were negative. Neuroblastoma or other malignancies were not found. She responded well to a corticosteroid-intravenous immunoglobulin (IVIG) combination and remained symptom-free for 3 years until presenting again with isolated ocular flutter. Brain MRI at this time remained atypical for classic multiple sclerosis (MS) with a predominance of juxtacortical demyelinating lesions. CSF was positive for oligoclonal bands. Serum myelin oligodendrocyte glycoprotein (MOG) antibodies were present. Ocular flutter can be the presenting feature of MOG antibody-associated pediatric demyelination.

Three new case reports of Arteriovenous malformation-related Amyotrophic Lateral Sclerosis.

Despite recent advances in genetics, in most cases of Amyotrophic Lateral Sclerosis (ALS) no etiological factor can be identified. Cerebral Arteriovenous Malformations (AVMs) have been associated with ALS development in a few studies, but the nature of this connection is unclear. We report here 3 additional cases of young adults, who had undergone repeated embolizations for complex AVMs, and who then developed, after many years, ALS symptoms and signs. In two of these cases Vascular Endothelial Growth Factor (VEGF) levels were found to be extremely high, in contrast to previous reports. Our 3 cases, together with the previously reported ones, suggest that a subgroup of patients with AVMs, with a particular profile of a complex nidus with repeated embolization procedures, are at increased risk of developing ALS. The reason for this association is unclear, but may relate to dysregulation of secreted vascular factors, as suggested by our VEGF results, or more broadly to the neurovascular hypothesis of ALS. Alternatively, a transneuronal type of neurodegeneration may be involved.

Trauma system in Greece: Quo Vadis?

INTRODUCTION: Implementation of trauma systems has markedly assisted in improving outcomes of the injured patient. However, differences exist internationally as diverse social factors, economic conditions and national particularities are placing obstacles. The purpose of this paper is to critically evaluate the current Greek trauma system, provide a comprehensive review and suggest key actions. METHODS: An exhaustive search of the - scarce on this subject - English and Greek literature was carried out to analyze all the main components of the Greek trauma system, according to American College of Surgeons' criteria, as well as the WHO Trauma Systems Maturity Index. RESULTS: Regarding prevention, efforts are in the right direction lowering the road traffic incidents-related death rate, however rural and insular regions remain behind. Hellenic Emergency Medical Service (EKAB) has well-defined communications and emergency phone line but faces problems with educating people on how to use it properly. In addition, equal and systematic training of ambulance personnel is a challenge, with the lack of pre-hospital registry and EMS quality assessment posing a question on where the related services are currently standing. Redistribution of facilities' roles with the establishment of the first formal trauma centre in the existing infrastructure would facilitate the development of a national registry and introduction of the trauma surgeon subspecialty with proper training potential. Definite rehabilitation institutional protocols that include both inpatient and outpatient care are needed. Disaster preparedness entails an extensive national plan and regular drills, mainly at the pre-hospital level. The lack, however, of any accompanying quality assurance programs hampers the effort to yield the desirable results. CONCLUSION: Despite recent economic crisis in Greece, actions solving logistics and organising issues may offer a well-defined, integrated trauma system without uncontrollably raising the costs. Political will is needed for reforms that use pre-existing infrastructure and working power in a more efficient way, with a first line priority being the establishment of the first major trauma centre that could function as the cornerstone for the building of the Greek trauma system.

An update of neurological manifestations of vasculitides and connective tissue diseases: a literature review / Atualização das manifestações neurológicas das vasculitides e das doenças do tecido conjuntivo: revisão de literatura

Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms.

As vasculites são um grupo heterogêneo de doenças autoimunes primárias ou secundárias a uma grande variedade de doenças infecciosas sistêmicas, malignas ou do tecido conjuntivo. Estas últimas são as que ocorrem com mais frequência, porém os mecanismos patogênicos ainda não foram plenamente determinados. Diversas e frequentes complicações do sistema nervoso central e periférico ocorrem nas vasculites e doenças do tecido conjuntivo. Em muitos casos, os distúrbios neurológicos têm evolução clínica atípica ou mesmo início precoce, ao que todos os profissionais de saúde devem estar cientes. O objetivo desta breve revisão foi atualizar os principais distúrbios neurológicos da vasculite comum e das doenças do tecido conjuntivo, visando ao diagnóstico e ao tratamento corretos, com ênfase nos mecanismos fisiopatológicos.

An update of neurological manifestations of vasculitides and connective tissue diseases: a literature review.

Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms.

Migraine and tension-type headache triggers in a Greek population / Fatores desencadeantes de enxaqueca e de cefaleia tipo tensional em uma população grega

Migraine and tension type headache are the two most common primary headaches. The purpose of this study was to detect differences in clinical characteristics and headache triggers and in a Greek cohort of 51 migraineurs and 12 patients with tension-type headache. (TTH) Migraine patients had a significantly lower age at headache onset and frequency, higher mean visual analogue scale (VAS) and greater maximum duration of headache episodes compared to TTH patients. They did not differ from (TTH) patients in quality of headache, laterality of pain, way of headache installation and progression and temporal pattern of headaches. Nausea, vomiting and phonophobia were more frequent in migraine. Triggering of headaches by dietary factors was associated with migraine, whereas there was no difference between the two groups in any of the other headache triggers. Stress, both physical and psychological, were particularly common in both patient groups.

Enxaqueca e cefaleia tipo tensional são as duas cefaleias primárias mais frequentes. O propósito deste estudo foi avaliar as diferenças e características dos fatores desencadeantes destas cefaleias numa coorte grega de 51 pacientes com enxaqueca e 12 com cefaleia tipo tensional. Pacientes com enxaqueca tinham uma idade significativamente menor por ocasião do início da cefaleia e maior frequência, maiores valores de (VAS) e maior duração dos episódios em comparação com os pacientes com (CTT). Não houve diferença entre os pacientes com enxaqueca e (CTT) com relação à qualidade e lateralidade da dor, na forma de instalação e progressão, e no padrão temporal das cefaleias. Náuseas, vômitos e fonofobia foram mais frequentes em enxaqueca. Fatores desencadeantes na dieta estavam associados à enxaqueca, enquanto não houve diferença entre os dois grupos para outros fatores desencadeantes. Estresse físico e psicológico foram particularmente prevalentes em ambos os grupos de pacientes.

Laparoscopic versus open mesh repair for recurrent inguinal hernia: a meta-analysis of outcomes.

BACKGROUND: The objective of this study was to examine the outcomes of comparisons between laparoscopic and open mesh repairs in the setting of recurrent inguinal hernia. METHODS: The electronic databases MEDLINE, Embase, Pubmed, and the Cochrane Library were used to search for articles from 1990 to 2008. The present meta-analysis pooled the effects of outcomes of a total of 1,542 patients enrolled into 5 randomized controlled trials and 7 comparative studies, using classic and modern meta-analytic methods. RESULTS: Significantly fewer cases of hematoma/seroma formation were observed in the laparoscopic group in comparison with the Lichtenstein group (odds ratio, .38; .15-.96; P = .04). A matter of great importance is the higher relative risk of overall recurrence in the transabdominal preperitoneal group compared with the totally extraperitoneal group (relative risk, 3.25; 1.32-7.9; P = .01). CONCLUSIONS: Laparoscopic versus open mesh repair for recurrent inguinal hernia was equivalent in most of the analyzed outcomes.