Lactate Profile Assessment-A Good Predictor of Prognosis in Patients with COVID-19 and Septic Shock Requiring Continuous Renal Therapy.

INTRODUCTION: Lactate is a useful prognostic marker, as its level increases in hypoxic tissue and/or during accelerated aerobic glycolysis due to excessive beta-adrenergic stimulation and decreased lactate clearance. The Surviving Sepsis Campaign Bundle 2018 Update suggests premeasurement of lactate within 2-4 h so that physicians perform, assist, administer, and introduce lactate-guided resuscitation to reduce mortality due to sepsis. METHODS: A total of 108 patients with septic shock who underwent continuous renal replacement therapy (CRRT) for acute kidney injury were enrolled in this observational study. Demographic, clinical, and laboratory data were collected, and patients were divided into two groups: survivors and non-survivors. RESULTS: Multivariate analysis demonstrated that lactate levels at 24 h after initiation of CRRT treatment, but not lactate levels at intensive care unit (ICU) admission, were associated with mortality. Lactate clearance was associated with lower mortality among the survivors (OR = 0.140) at 6 h after ICU admission and late mortality (OR = 0.260) after 24 h. The area under the ROC curves for mortality was 0.682 for initial lactate; 0.797 for lactate at 24 h; and 0.816 for lactate clearance at 24 h. CONCLUSIONS: Our result reinforces that the determination of lactate dynamics represents a good predictor for mortality, and serial lactate measurements may be more useful prognostic markers than initial lactate in patients with septic shock.

Code Stroke Alert: Focus on Emergency Department Time Targets and Impact on Door-to-Needle Time across Day and Night Shifts.

BACKGROUND AND OBJECTIVES: To minimize stroke-related deaths and maximize the likelihood of cerebral reperfusion, medical professionals developed the "code stroke" emergency protocol, which allows for the prompt evaluation of patients with acute ischemic stroke symptoms in pre-hospital care and the emergency department (ED). This research will outline our experience in implementing the stroke code protocol for acute ischemic stroke patients and its impact on door-to-needle time (DTN) in the ED. METHODS: Our study included patients with a "code stroke alert" upon arrival at the emergency department. The final sample of this study consisted of 258 patients eligible for intravenous (IV) thrombolysis with an onset-to-door time < 4.5 h. ED admissions were categorized into two distinct groups: "day shift" (from 8 a.m. to 8 p.m.) (n = 178) and "night shift" (from 8 p.m. to 8 a.m.) (n = 80) groups. RESULTS: An analysis of ED time targets showed an increased median during the day shift for onset-to-ED door time of 310 min (IQR, 190-340 min), for door-to-physician (emergency medicine doctor) time of 5 min (IQR, 3-9 min), for door-to-physician (emergency medicine doctor) time of 5 min (IQR, 3-9 min), and for door-to-physician (neurologist) time of 7 min (IQR, 5-10 min), also during the day shift. During the night shift, an increased median was found for door-to-CT time of 21 min (IQR, 16.75-23 min), for door-to-CT results of 40 min (IQR, 38-43 min), and for door-to-needle time of 57.5 min (IQR, 46.25-60 min). Astonishingly, only 17.83% (n = 46) of these patients received intravenous thrombolysis, and the proportion of patients with thrombolysis was significantly higher during the night shift (p = 0.044). A logistic regression analysis considering the door-to-needle time (minutes) as the dependent variable demonstrated that onset-to-ED time (p < 0.001) and door-to-physician (emergency medicine physicians) time (p = 0.021) are predictors for performing thrombolysis in our study. CONCLUSIONS: This study identified higher door-to-CT and door-to-emergency medicine physician times associated with an increased DTN, highlighting further opportunities to improve acute stroke care in the emergency department. Further, door-to-CT and door-to-CT results showed statistically significant increases during the night shift.

Risk Assessment of Venous Thromboembolism among Septic Shock Patients: Single versus Concurrent Insertion of Central Venous Catheters.

Background and Objectives: Thrombosis is a serious complication experienced by some hospitalized patients. While concurrent placement of two catheters (CVCs) in the same central vein offers several benefits in clinical settings, we aimed to investigate the role of this procedure in relation to the risk of thrombosis. Materials and Methods: Over a two-year retrospective analysis, we examined 114 patients with septic shock caused by a pulmonary infection, who underwent the insertion of one or more central lines into a central vein during their ICU stay. Logistic regression models were employed to assess the correlation between the Caprini risk score, the placement of two CVCs in the same vein, COVID-19 infection and the risk of venous thromboembolism (VTE). Results: In total, 53% of the patients underwent the concurrent insertion of two CVCs. The placement of two CVCs in the same vein appears to elevate the VTE risk by 2.5 times (95% CI: 1.03-6.12). Logistic regression analysis indicated that hemodialysis catheters amplify the VTE risk by nearly five times, even when accounting for a series of factors (95% CI: 1.86-12.31). Conclusions: Our study suggests that the elevated risk of VTE is likely associated with the insertion of the hemodialysis catheters rather than solely the presence of two concurrent catheters.

Lactate Levels and Clearance: Key Predictors of Prognosis for COVID-19 and Non-COVID-19 Septic Shock Patients in the Emergency Department.

BACKGROUND: This investigation assesses the prognostic value of lactate levels and their clearance in septic shock patients, particularly emphasizing the comparative analysis between COVID-19 and non-COVID-19 patients in the emergency department. This study aims to elucidate the unique prognostic implications of lactate dynamics in these distinct patient groups, thereby enhancing the management of septic shock. METHODS: An observational prospective study was conducted, enrolling 114 septic shock patients from the Emergency County Hospital Resita, Romania, categorizing them into COVID-19 and non-COVID-19 groups to examine their initial lactate levels, clearance rates, and their correlation with patient outcomes. RESULTS: This study identified significant differences in the initial lactate levels and clearance rates between the two groups, indicating higher initial lactate levels and slower clearance rates in COVID-19 patients. Survivors demonstrated significantly lower initial lactate levels (1.5 ± 0.4 mmol/L) and higher lactate clearance rates (33 ± 15%) compared to non-survivors (2.5 ± 0.5 mmol/L and 24 ± 9%, respectively; lactate levels p = 0.001, clearance rates p = 0.002). CONCLUSIONS: Lactate monitoring, particularly clearance rates, is crucial in the prognostic assessment of septic shock patients. These findings highlight the need for targeted interventions in COVID-19 patients to improve outcomes, underscoring lactate dynamics as a vital component of septic shock management in differing patient populations.

Special Issue: Emergency Medicine: Clinical Advances and Challenges in Diagnosis and Treatment.

The development of Emergency Medicine brings various challenges [...].

The Learning Experience of Romanian Medical Students During the Online Teaching Imposed by the COVID-19 Pandemic.

Introduction: The COVID-19 pandemic has disrupted many aspects of society, including medical education. In response to the pandemic, Romanian medical schools and universities have turned to online learning as a means of continuing instruction while maintaining social distancing protocols. While online learning in medical education was utilized prior to the pandemic, its widespread adoption has brought both challenges and opportunities to the field. The purpose of this study was to assess medical students' perception towards implementing E-learning during COVID 19 pandemic. Material and Methods: This cross-sectional multicentric study comprised 611 medical students from several medical university centers from Romania. A self-developed questionnaire was online applied between January and March 2021 and used for the evaluation and analysis of perceived changes in teaching before and during the COVID-19 pandemic. Results: Most students (n = 71.5%) considered that the pandemic had an overall negative impact on their professional development. A significant negative correlation (p < 0.01, for all), was observed between during COVID-19 pandemic and the level of medical training, motivation to learn, and level of self-confidence. Conclusion: The shift to online learning during the pandemic decreased the psychological and professional development of medical students, resulting in a low perception of self-confidence, motivation, and practical involvement. However, there are many benefits brought by the use of electronic technologies for medical education both in Romania and in the world. These benefits should be systematically evaluated, and effective strategies should be developed to permanently improve the e-learning methods of these students.

First Identification and Molecular Characterization of Trichinella britovi (Nematoda: Trichinellidae) from the Pine Marten (Martes martes Linnaeus, 1758) in Romania.

Trichinella spp. are etiological zoonotic agents spread throughout the world and affect mammals, birds, and reptiles; they evolve via two cycles: domestic and sylvatic. Martes martes is a carnivorous nocturnal mammal from the family Mustelidae. In Romania, this host is widespread in all forests of the country. Martes martes has an extremely voracious appetite, feeding on fruit and also on a variety of small animals, including rodents such as mice and rats. The aim of this study was the identification and molecular characterization of Trichinella larvae isolated from the muscle tissue of Martes martes collected in different counties of Romania. The muscle samples were examined via artificial digestion, and the larvae were identified at the species level via multiplex PCR. The presence of larvae belonging to Trichinella britovi, a species frequently identified in wild carnivores in temperate zones, was observed. Although T. britovi has been already reported in several host species in Romania, this is the first time this species has been observed in a Martes martes specimen. This finding contributes to our knowledge about the host species involved in the maintenance of the Trichinella sylvatic cycle in Romania, and it confirms that this parasite is consistently present in the wild fauna of this country.

Epidemiology of Cryptosporidium Infection in Romania: A Review.

Since 1983, when the first report of a human Cryptosporidium spp. infection was published in Romania, and until now, many studies on cryptosporidiosis have been published in our country, but most of them are in the Romanian language and in national journals less accessible to international scientific databases. Although the infection was first recognized as a problem in children or immunocompromised people or more of a problem in low-income or underdeveloped global countries, we have shown in this review that it can also occur in people with normal immunological function and that the epidemiology of our country can provide a theoretical basis for the formulation of a Cryptosporidium spp. prevention strategy. In addition, 9.1% of healthy children and 73% of immunocompromised children were observed to have Cryptosporidium spp. infections. Higher rates have also been reported in immunocompromised adults (1.8-50%). Analyzing the prevalence of Cryptosporidium spp. infection in animals, we found values of 28.52% in cattle, 18% in buffalo calves, between 27.8 and 60.4% in pigs, 52.7% in dogs, and 29.4% in cats. Furthermore, in Romania, the burden of cryptosporidiosis, including acute infections and long-term sequelae, is currently unknown.

Emergency Department Time Targets for Interhospital Transfer of Patients with Acute Ischemic Stroke.

Background and objectives: Although the intravenous tissue plasminogen activator (rt-PA) has been shown to be effective in the treatment of acute ischemic stroke (AIS), only a small proportion of stroke patients receive this drug. The low administration rate is mainly due to the delayed presentation of patients to the emergency department (ED) or the lack of a stroke team/unit in most of the hospitals. Thus, the aim of this study is to analyze ED time targets and the rate of rt-PA intravenous administration after the initial admission of patients with AIS in an ED from a traditional healthcare center (without a neurologist or stroke team/unit). Methods: To analyze which factors influence the administration of rt-PA, we split the general sample (n = 202) into two groups: group No rt-PA (n = 137) and group rt-PA (n = 65). This is based on the performing or no intravenous thrombolysis. Results: Analyzing ED time targets for all samples, we found that the median onset-to-ED door time was 180 min (IQR, 120-217.5 min), door-to-physician time was 4 min (IQR, 3-7 min), door-to-CT time was 52 min (IQR, 48-55 min), and door-in-door-out time was 61 min (IQR, 59-65 min). ED time targets such as door-to-physician time (p = 0.245), door-to-CT time (p = 0.219), door-in-door-out time (p = 0.24), NIHSS at admission to the Neurology department (p = 0.405), or NIHSS after 24 h (p = 0.9) did not have a statistically significant effect on the administration or no rt-PA treatment in patients included in our study. Only the highest door-to-CT time was statistically significantly correlated with the death outcome. Conclusion: In our study, the iv rt-PA administration rate was 32.18%. A statistically significant correlation between the highest door-to-CT time and death outcome was found.

Beyond the Digital Competencies of Medical Students: Concerns over Integrating Data Science Basics into the Medical Curriculum.

Introduction. Data science is becoming increasingly prominent in the medical profession, in the face of the COVID-19 pandemic, presenting additional challenges and opportunities for medical education. We retrospectively appraised the existing biomedical informatics (BMI) and biostatistics courses taught to students enrolled in a six-year medical program. Methods. An anonymous cross-sectional survey was conducted among 121 students in their fourth year, with regard to the courses they previously attended, in contrast with the ongoing emergency medicine (EM) course during the first semester of the academic year 2020−2021, when all activities went online. The questionnaire included opinion items about courses and self-assessed knowledge, and questions probing into the respondents' familiarity with the basics of data science. Results. Appreciation of the EM course was high, with a median (IQR) score of 9 (7−10) on a scale from 1 to 10. The overall scores for the BMI and biostatistics were 7 (5−9) and 8 (5−9), respectively. These latter scores were strongly correlated (Spearman correlation coefficient R = 0.869, p < 0.001). We found no correlation between measured and self-assessed knowledge of data science (R = 0.107, p = 0.246), but the latter was fairly and significantly correlated with the perceived usefulness of the courses. Conclusions. The keystone of this different perception of EM versus data science was the courses' apparent value to the medical profession. The following conclusions could be drawn: (a) objective assessments of residual knowledge of the basics of data science do not necessarily correlate with the students' subjective appraisal and opinion of the field or courses; (b) medical students need to see the explicit connection between interdisciplinary or complementary courses and the medical profession; and (c) courses on information technology and data science would better suit a distributed approach across the medical curriculum.

A rare encounter with two cases of Budd­Chiari syndrome in the Emergency Department: A case report.

Budd-Chiari syndrome (BCS) is a rare disorder clinically characterized by abdominal pain, hepatomegaly and ascites. The condition is often related to thrombosis of the hepatic veins or the terminal portion of the inferior vena cava. A myeloproliferative disorder is the most identified underlying prothrombotic risk factor, although almost one-half of affected patients are now recognized as having multiple underlying prothrombotic risk factors. Doppler ultrasound may be enough to confirm the diagnosis of BCS; however, computed tomography or magnetic resonance imaging is often employed. Anticoagulant therapy is the cornerstone of BCS treatment, but most patients also need additional treatment strategies. Most patients with BCS are now treated by endovascular intervention, which has improved survival rate in those afflicted by this disease. The long-term course of the disease can be complicated by progression or recurrence of the underlying myeloproliferative disorder. The present study reports the cases of two patients with BCS with the aim of alerting healthcare workers in Emergency Departments of this less common diagnosis in patients presenting with frequent complaints of abdominal pain.

Risk Factors, Characteristics, and Outcome in Non-Ventilated Patients with Spontaneous Pneumothorax or Pneumomediastinum Associated with SARS-CoV-2 Infection.

BACKGROUND AND OBJECTIVES: Spontaneous pneumothorax (SP) and spontaneous pneumomediastinum (SPM) have frequently been cited as complications associated with coronavirus disease 2019 (COVID-19) pneumonia, with especially poor prognosis in mechanically ventilated patients. The current literature is controversial regarding the potential risk factors for developing SP or SPM (SP-SPM) in non-ventilated COVID-19 patients. Our research addressed a twofold objective: (a) to investigate the characteristics of patients with SP-SPM (both with and without COVID-19) and compare them to patients with sole COVID-19; (b) to quantify the risk of in-hospital mortality associated with SP-SPM and COVID-19. PATIENTS AND METHODS: A retrospective case-control study was conducted in the emergency departments (ED) of two tertiary hospitals in Timisoara, Romania, over one year (1st April 2020‒31st March 2021; 64,845 records in total) and 70 cases of SP-SPM were identified (both SARS-CoV-2 positives and negatives). The control group comprised COVID-19 patients with no SP-SPM, included at a 2:1 ratio. Logistic regression was employed to quantify the in-hospital mortality risk associated with age, SP-SPM, and COVID-19. RESULTS: SP-SPM and COVID-19 were connected with prolonged hospitalization, a higher percentage of intensive care admission, and a higher mortality. SP-SPM increased the odds of death by almost four times in patients of the same age, gender, smoking status, and SARS-CoV-2 infection: OR = 3.758, 95% CI (1.443-9.792). Each additional year of age added 9.4% to the mortality risk: OR = 1.094, 95% CI (1.054-1.135). CONCLUSION: ED physicians should acknowledge these potential risks when attending COVID-19 patients with SP-SPM.

Using 360-degree video for teaching emergency medicine during and beyond the COVID-19 pandemic.

OBJECTIVE: During the COVID-19 pandemic, emergency medicine (EM) teachers had to employ innovative methods to ensure the continuity of the education process. The purpose of this study was to explore the adequacy of the 360-degree video (video 360) technology in EM education in the context of: (a) students' attitudes towards the video 360; (b) students' academic performance in their required examination at the end of the EM course compared to the assessment results of students from the previous academic year. METHODS: A mixed-method research project enrolled the fourth-year medical students who attended the required EM course during the first semester of the academic year 2020-2021 when all activities with undergraduate students went online and teaching scenarios recorded in the video 360 format were employed. Data collection was two-fold: (a) anonymous questionnaires, complemented with basic YouTube analytics; (b) multiple-choice questionnaires (MCQ) and oral examination, contrasting the results with those in 2019-2020. Data analysis used descriptive statistics and non-parametric methods. RESULTS: Seventy-nine students (53 females and 26 males) participated in the project and all completed the EM course. Students' interest in and their acceptance of the video 360 technology were high (total scoring in the upper 20% of the respective scales), with consistently good performance in two parallel, independent, interview-based oral/practical evaluations (Spearman correlation coefficient R = 0.665, p < .001). The majority scored over 90% in the summative MCQ, with higher values compared to their colleagues' during the previous academic year (with on-site teaching): scoring percentages with mean ± standard deviation of 92.52 ± 4.57 and 76.67 ± 18.77, respectively. CONCLUSION: Our project showed that the video 360 scenarios were effective in teaching EM. In the long term, employing this accessible and inexpensive educational approach would add value to on-site training by enriching the exposure to a specific ED environment.KEY MESSAGESMedical students valued the 360-degree video scenarios as contributing substantially to their EM knowledge and preparedness.Examination results confirmed the 360-degree video scenarios as viable in EM teaching.The 360-degree video technology would be a sustainable solution for hybrid medical teaching in the long term.

Case Report: Massive Spontaneous Pneumothorax-A Rare Form of Presentation for Severe COVID-19 Pneumonia.

Background and Objectives: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a viral disease that is spreading worldwide and became a pandemic. Although most of the time, the symptoms of the infection are flu like, a percentage of patients develop severe forms, along with severe complications. Many of them are known among front-line health workers, but the number of uncommon presentations and complications has increased. This case report aims to alert healthcare workers on less common forms of presentation, and to introduce this differential diagnosis in the evaluation of patients with COVID-19, given the increasing occurrence of pneumothorax in patients who are not mechanical ventilated. Case presentation: A 57-year-old female patient came to the Emergency Department (ED) by ambulance, with acute respiratory failure. She had SpO2 = 43% on room air at home, and 86% on admission in ED after oxygen delivery (on a reservoir mask). SARS-CoV-2 infection was suspected based on symptoms that started three days ago (fever, dry cough, dyspnea, and fatigability). Blood was taken for lab tests, pharyngeal and nasal swabs for the reverse transcription-PCR (RT-PCR) test, and native computed tomography (CT) was scheduled. The thoracic CT scan showed massive right pneumothorax, partially collapsed lung, multiple bilateral lung infiltrates with a ground glass aspect and the RT-PCR test came back positive for SARS-CoV-2 infection. Despite the prompt diagnosis and treatment of pneumothorax (thoracostomy was performed and the drain tube was placed), the patient died after a long hospitalization in the intensive care unit. Conclusion: Secondary spontaneous pneumothorax (SSP), as a complication in severe forms of COVID-19 pneumonia, especially in female patients without risk factors is rare, and early diagnosis and treatment are essential for increasing the survival chances of these patients.

Contribution of the cyto-histopathological diagnosis and ultrastructural parameters to the evaluation of maxillary cysts - a 10-year multidisciplinary approach.

Diagnostic and treatment plans in cystic jawbone tumors are often difficult to address. The etiopathogenic links involved in cell-matrix differentiation disorders are complex. Quantification of the inflammatory process in the evolution of cystic odontogenic lesions highlights a particular reactivity of the host, especially age-dependent and the endodontic-periodontal space interrelation, drawing attention to the difficulties of etiopathogenic, evolution, prognostic and treatment of these lesions. Difficulties in histopathological (HP) diagnosis are reported by the lack of morphofunctional integration of dental tissues, both topographically and evolutionarily, especially when odontogenic epithelial remains in the cystic wall, reactive bone condition, appearance and condition of the reactive epithelium are overlooked. In this study, we developed an interdisciplinary approach for the dynamics of tissue morphology found in the walls of maxillary cysts. Failure to recognize the tissues that form the cystic lesion leads to misinterpretations of pathology and to the wrong classification in the group of maxillary cysts. We analyzed by different techniques 564 biopsy fragments from maxillary cystic lesions, most of which are clinically classified as inflammatory or odontogenic ones. From our experience, we reevaluated the lesions with cystic changes and completed the diagnosis in 10-12% of cases. The most common maxillary cystic lesion encountered by us was the root cyst, an inflammatory dental cyst, which has been over diagnosed clinically, radiologically and histopathologically. Recognition and selection of embryonic remnants from odontogenesis is crucial for the HP diagnosis of maxillary cysts, allowing the clinician to monitor treatment or to develop evolutionary-prognostic perspectives of odontogenic cystic lesions.

Invasive pulmonary infection due to Thermoascus crustaceus in a kidney transplant recipient.

The first case of invasive pulmonary infection due to the thermophilic fungus Thermoascus crustaceus in a kidney transplant recipient is described. For the identification of the fungal isolate, morphological aspects and molecular analysis have been used. The case report emphasizes this fungal species as an opportunistic human pathogen and underlines the importance of an accurate laboratory diagnosis for the correct management of the patient.

Correlations between bone turnover markers, serum magnesium and bone mass density in postmenopausal osteoporosis.

INTRODUCTION: Bone mass density (BMD) is still the gold standard for the diagnosis of osteoporosis, but bone turnover markers (BTMs) can provide helpful information regarding the bone remodeling process. The aim of this study was to determine the correlations between BMD and serum levels of BTMs (tartrate-resistant acid phosphatase-5b [TRAP-5b]), bone-specific alkaline phosphatase (BSAP), estradiol (E2), and magnesium (Mg[2+]) ion concentrations in postmenopausal osteoporotic women as compared to healthy postmenopausal subjects. MATERIALS AND METHODS: The study included 132 women with postmenopausal osteoporosis and 81 healthy postmenopausal women without osteoporosis. Dual-energy X-ray absorptiometry scan assessed BMD at different skeleton sites. Serum levels of E2, BSAP, and TRAP-5b were measured by enzyme linked immunosorbent assay. Serum levels of Mg(2+) were determined using the colorimetric spectrometry technique. RESULTS: Serum levels of BTMs were significantly higher in osteoporotic women than in controls. BSAP has a moderate sensitivity (76.5%) and specificity (84.3%) (cutoff point 21.27 U/L). At a cutoff point of 3.45 U/L, TRAP-5b presented a sensitivity of 86.3% and a higher specificity of 90.6%. Osteoporotic patients showed significantly lower concentrations of serum Mg(2+) than the control group. Mg(2+) levels correlated positively with BMD values (r=0.747, P<0.0001). Furthermore, Mg(2+) concentrations correlated positively with E2 levels (r=0.684, P<0.0001). Spine BMD correlated negatively with BSAP levels (r=-0.36, P<0.0001). CONCLUSION: Our study showed that BMD correlates negatively with BTMs and positively with E2 and Mg(2+) levels. TRAP-5b presents a good specificity in identifying patients with postmenopausal osteoporosis.

Disodium Cromolyn and Anti-podoplanin Antibodies Strongly Inhibit Growth of BHK 21/C13-derived Fibrosarcoma in a Chick Embryo Chorioallantoic Membrane Model.

AIM: To characterize baby hamster kidney fibroblast (BHK 21/C13) cells and test the effects of antibodies against podoplanin and disodium cromolyn on BHK 21/C13 cell line-derived tumors grown on chick embryo chorioallantoic membrane (CAM). MATERIAL AND METHODS: BHK 21/C13 cell-derived fibrosarcomas developed in hamsters were implanted on CAM and treated with anti-podoplanin antibodies and disodium cromolyn. BHK 21/C13 cell immunophenotype was assessed. RESULTS: Fibrosarcoma cells were positive for vimentin, CD117, smooth muscle actin, vascular endothelial growth factor epidermal growth factor receptor, homebox prospero gene 1 and negative for platelet-derived growth factor B, neuron-specific enolase, S100, CD34, Ewing sarcoma and podoplanin. CAM-grown fibrosarcomas were highly sensitive to disodium cromolyn and anti-podoplanin antibodies. CONCLUSION: Immunophenotyping BHK 21/C13 cells and their response to drugs represent the first step in revealing cell line utility and a reliable tool for experimental cancer research.

The Mesenchymal-Epithelial and Epithelial-Mesenchymal Cellular Plasticity of Liver Metastases with Digestive Origin.

BACKGROUND: Few data are available regarding the epithelial to mesenchymal transition (EMT) /mesenchymal to epitheilal transition (MET) in the liver metastasis of digestive cancers. The aim of this study was to establish EMT/MET metastatic tumor cell plasticity according to the histological growth pattern of liver metastases. MATERIALS AND METHODS: Biopsies from 25 patients with liver metastasis (desmoplastic, replacement and pushing type) were evaluated. Double immunostaining of E-cadherin/vimentin, keratin 8,18/vimentin and E-cadherin/ keratin 8,18 were performed. RESULTS: The following cell types were noted: epithelial, mesenchymal, non-differentiated and differentiated hybrid mesenchymal/ epithelial and non-hybrid phenotype. All cases had mesenchymal/ epithelial phenotype cells. A significant correlation was found between the non-differentiated hybrid mesenchymal/ epithelial phenotype metastatic cells and histological growth pattern for gastric and colorectal cancer. CONCLUSION: A MET-targeting strategy, in conjunction with conventional chemotherapy, may be useful for the treatment of liver metastases.

Endothelial Cell Proliferation and Vascular Endothelial Growth Factor Expression in Primary Colorectal Cancer and Corresponding Liver Metastases.

BACKGROUND: . Colorectal carcinoma (CRC) is one of the major causes of cancer death worldwide. Data from the literature indicate differences between the proliferation rate of endothelial cells relative to the morphology growth type, possibly due to origin of specimens (autopsy material, surgery fragments) or quantification methods. Vascular endothelial growth factor (VEGF) is a factor that stimulates the proliferation of endothelial cells. It is expressed in more than 90% of cases of metastatic CRC. AIM: The aim of this study was to evaluate the endothelial cell proliferation and VEGF expression in primary tumors and corresponding liver metastases. MATERIALS AND METHODS: Our study included 24 recent biopsies of primary tumors and corresponding liver metastases of CRC cases. CD34/ Ki67 double immunostaining and RNA scope assay for VEGF were performed. RESULTS: In the primary tumors analysis of VEGFmRNA expression indicated no significant correlation with differentiation grade, proliferative and non-proliferative vessels in the intratumoral and peritumoral areas. In contrast, in the corresponding liver metastases, VEGFmRNA expression significantly correlated with the total number of non- proliferative vessels and total number of vessels. CD34/ Ki67 double immunostaining in the cases with poorly differentiated carcinoma indicated a high number of proliferating endothelial cells in the peritumoral area and a low number in the intratumoral area for the primary tumor. Moderately differentiated carcinomas of colon showed no proliferating endothelial cells in the intratumoral area in half of the cases included in the study, for both, primary tumor and liver metastasis. In well differentiated CRCs, in primary tumors, a high proliferation rate of endothelial cells in the intratumoral area and a lower proliferation rate in the peritumoral area were found. A low value was found in corresponding liver metastasis. CONCLUSIONS: The absence of proliferative endothelial cells in half of the cases for the primary tumors and liver metastases in moderately differentiated carcinoma suggest a vascular mimicry phenomenon. The mismatch between the total number of vessels and endothelial proliferation in primary tumors indicate that a functional vascular network is already formed or the existence of some mechanisms influenced by other angiogenic factors.