Comparison of face anthropometry and digital 2D face photogrammetry as a method for predicting vertical dimension of occlusion.

PURPOSE: The objective of the study was to determine the values of 15 craniofacial linear distances in the Serbian ethnic group and the correlations between them that are predictive or can serve as proxy for OVD using and compare two methods of face-anthropometric and digital 2D face-photogrammetric measurement. MATERIAL AND METHODS: A total of 90 adults were selected. Facial distance as a tool to measure the OVD was Sn-Gn - distance between septum of the nose (Sn) and tip of the chin (Gn). Face-anthropometric measurements were made with a Boley Gauge (Buffalo Dental Manufacturing Co.NY,USA). Digital 2D photogrammetric facial measurements were performed using the computer program DrCeph (FYI Technologies, USA). RESULTS: Determined mean value for the distance Sn-Gn by face-anthropometric was Sn-Gn(f) X=63.55 and by face-photogrammetric was Sn-Gn(ph) X=63.56. Multivariate regression analysis revealed that Sn-Gn(f) depended on ExL-ExR(f) p<0.001, ZyL-ZyR(f) p=0.077, N-Sn(f) p=0.096, Sn-Sto(f) p=0.043 and gender and that Sn-Gn(ph) depended on ExL-ExR(ph) p<0.001, EnL-EnR(ph) p=0.029, N-Sn(ph) p=0.013, Sn-Sto(ph) p=0.001 and gender. CONCLUSIONS: A comparison of facial anthropometry and digital 2D facial photogrammetry reveals no statistical significance differences in the values obtained and shows that facial photogrammetry could be a reliable method as a facial anthropometry.

The Importance of Immunohistochemical Heterogeneous Expression of MMR Protein in Patients with Colorectal Cancer in Stage II and III of the Disease.

Background and objectives: In patients with colorectal cancer (CRC), heterogeneous expression of Mismatch repair (MMR) proteins can manifest itself in several different forms and is not such a rare phenomenon. Therefore, it is very important to recognize the nuclear expression of MMR proteins of different MMR status in order to avoid false positive or false negative results. The aim of this study was to determine the frequency and distribution of heterogeneous expression of MMR proteins in patients with stages II and III of the disease as well as its association with clinical, demographic and pathological characteristics of CRC in relation to proficient and deficient expression of MMR proteins. Material and Methods: The study included 104 cases of colorectal cancer obtained from surgical colectomy material in stages II and III of the disease. Results: From a total of 104 patients with colorectal cancer, immunohistochemical analysis of the expression of all four MMR proteins showed that heterogeneous expression of MMR proteins (as well as deficient immunoreactivity of tumor cells) was present in 12 cases, while proficient expression of MMR proteins was detected in 80 tumors. Conclusions: Our study showed that the only independent predictors of the loss of MMR protein expression were younger patient age and right-sided anatomical location of the tumor. The study also established the existence of heterogeneous expression of MMR proteins in a non-negligible percentage of CRCs (11.5%), where heterogeneous nuclear expression of MMR proteins was described in several different forms.

Cytomorphometric and Clinical Changes in Gingival Tissue after Subgingival Tooth Preparation-A Pilot Study.

Tooth preparation for a metal-ceramic crown with a subgingival finish line can lead to inflammatory changes in the gingival tissue, often accompanied by cell damage. This study aimed to evaluate the clinical signs of inflammation and the cytomorphological status of the gingival tissue before and after tooth preparation. The research included a homogeneous group of 19 patients with an indication for upper canine preparation. Before and after treatment, the gingival and the gingival bleeding indexes were determined, gingival swabs were taken, and direct smears prepared on slides for cytomorphometric analysis. The values of the measured gingival indexes were statistically significantly higher (p < 0.001) after tooth preparation. They decreased over time, which indicated the reversibility of the resulting changes. Cytological examination showed no statistically significant difference between the values of nuclear area, perimeter, Feret diameter, Feret angle, integrated optical density, MinFeret, and roundness, before and after the treatment. Significantly higher values of circularity, integrated optical density, MinFeret (p < 0.05), as well as roundness (p < 0.001) were found after 72 h, compared to those taken 15 min after tooth crown preparation. This study is a pioneering attempt to show gingival changes during fixed prosthodontic treatment and may shed new light on pathogenetic events in prosthodontic patients.

Developmental Characteristics of the Glomerular and Tubular Portion of the Nephron in the Human Foetal Kidney Cortex: Morphometrical and Immunohistochemical Analysis.

This study aimed to morphometrically examine the development of glomeruli and tubules in the kidney cortex of human foetuses at different gestational ages (GAs). We also investigated the expression of the proliferation marker Ki-67 and apoptosis-related markers Bcl-2 and Bax during nephrogenesis using immunohistochemistry. Kidney samples from 38 human foetuses of both sexes with GA ranging from 13 to 40 weeks were analysed. The samples were divided into 7 groups based on GA, each corresponding to 1 lunar month. Foetal kidneys showed a spatiotemporal gradient of nephron differentiation with the transient stages of nephron anlage located in the nephrogenic zone and immature nephrons located in the subjacent maturation zone. In the inner cortex, nephrons establish the morphological characteristics of definitive nephrons. The average area, perimeter, and Feret's diameter of the glomeruli formed within the kidney cortex gradually decreased up to a period of 29-32 weeks of gestation and subsequently increased until a period of 37-40 weeks. There was a weak negative correlation with GA. In contrast, the areal density of glomeruli increased up to a period of 21-24 weeks and then gradually decreased until a period of 37-40 weeks, showing a moderate negative correlation with GA. The average area of renal tubules slightly decreased until a period of 21-24 weeks of gestation and then gradually increased until a period of 36-40 weeks, showing a moderate positive correlation with GA. The average areal density of renal tubules increased significantly until a period of 21-24 weeks of gestation, remained relatively constant until a period of 33-36 weeks, and then increased significantly at 36-40 weeks. There was a strong positive correlation with GA. Our results showed that Ki-67 was expressed in numerous cells of the metanephric mesenchyme, pretubular aggregates, renal vesicles, comma-shaped bodies, and early S-shaped bodies. During subsequent development and the spatial expansion of nephrons towards the mature zone, the expression of Ki-67 was markedly reduced. Similarly, Bcl-2 was strongly expressed in induced nephrogenic progenitor cells, pretubular aggregates, renal vesicles, and comma-shaped bodies. As vascularisation and maturation of the nephron proceeded, Bcl-2 staining became less intense and limited to the parietal layer of the Bowman's capsule and renal tubules. Weak Bax expression was observed in individual scattered cells within segments of the nephrons at all developmental stages. In the mature zone, more intense Bax staining was observed in the renal tubules.

Idiopathic True Radial Artery Aneurysm: A Rare Case Report.

Idiopathic true aneurysm of the distal radial artery is a rare disease with only few reported cases. Most patients were treated surgically with proximal and distal arterial ligatures, while there are reports of only 7 cases where revascularization procedures were performed. We present a case of a 66-year-old man with a pulsatile mass in the right forearm at the location of the radial artery. Six months preceding the presentation, the patient had first noticed a pulsatile tumefaction which gradually increased in size, with a sudden increase during the last month. The patient worked as a waiter and was a non-smoker with no significant comorbidities. There was no history of trauma, recent infection, hospitalization, recurrent injury, or peripheral venous cannulation. After CDT diagnosis, we performed resection of aneurysm and reconstruction with cephalic autovenous graft. One month afterwards, at the follow-up visit, the patient denied having symptoms of hand ischemia and duplex ultrasound examination showed adequate patency of the radial artery. This paper presents a rare case of a true idiopathic radial artery aneurysm that was treated surgically by complete resection and interposition with a reverse cephalic vein autovenous graft. Detailed anamnesis and clinical examination are necessary for the appropriate surgical treatment of the disease.

The hepatoprotective effect of aminoguanidine in acute liver injury caused by CCl4 in rats.

In this study, the hepatoprotective effect of aminoguanidine in acute liver damage caused by carbon tetrachloride-CCl4 at a dose of 1 mL/kg, i.p. was investigated in experimental rats. Ten days of preventive treatment with aminoguanidine before exposure to toxic CCl4, at a dose of 150 mg/kg, i.p., led to significant reduction in biochemical markers of acute liver injury-AST(p < 0.001), ALT (p < 0.01), SDH (p < 0.05) and reduction in pro-oxidative markers-H2O2 (p < 0.05), TOS (p < 0.01), TBARS, and LOOH (p < 0.001) in relation to rats treated only CCl4. Treatment with aminoguanidine resulted in a significant reduction in the consumption of antioxidant-GR (p < 0.01), GST, GPx, GSH (p < 0.001), and a decrease in pro-inflammatory-TNF-α (p < 0.01), IL-1ß, IL-6, NO and NGAL (p < 0.001) markers relative to animals exposed to CCl4 alone. Also, aminoguanidine pre-treatment leads to an increase in arginase activity (p < 0.001), and a decrease in citrulline concentration (p < 0.01), as well as polyamine catabolism enzyme activity-putrescin oxidase and spermine oxidase (p < 0.001) in comparison to the CCl4 group. Aminoguanidine led to a striking reduction of the necrotic field (p < 0.001), and a significant increase in the number of apoptotic hepatocytes (p < 0.001), as well as the proapoptotic markers-BAX and Caspase-3 (p < 0.05), compared to CCl4. The hepatoprotective mechanisms in CCl4 induce hepatotoxicity of aminoguanidine are based on the strong antioxidant effects, inhibition of pro-oxidative and pro-inflammatory mediators, as well as induction of damaged hepatocytes into apoptosis.

Lycopene and Caffeic Acid Phenethyl Ester Affect Caspase-3 Activity, but Do Not Alter the NO Pathway in Lung Tissue Damage Induced by Cisplatin.

INTRODUCTION: Antioxidants such as lycopene (LCP) and caffeic acid phenethyl ester (CAPE) represent ideal molecules for the treatment of different reactive oxygen species (ROS) associated disorders. Cisplatin is a chemotherapeutic agent, causing an increase in ROS and DNA damage, with numerous side effects, which include lung toxicity. In the presents study, we evaluated and mutually compared the potential of LCP and CAPE in preventing cisplatin-induced rat lung damage. METHODS: The study was done using pathohistological analysis and a panel of biochemical parameters that reflect lung oxidative tissue damage, inflammation, and apoptosis. RESULTS: The obtained results suggest that cisplatin (10 mg/kg) causes significant disturbances in the lung tissue morphology, followed by an increase in lipid peroxidization and protein modification. Also, a pronounced inflammatory response and cell apoptosis cascade activation was noted. Both LCP and CAPE were able to mitigate the changes, to a different extent, in oxidative damage and apoptosis progression induced by cisplatin. However, they both had limited effect on inflammation since they only prevented an increase in myeloperoxidase activity but had not been able to prevent the NO generation. CONCLUSION: It is hard to be exact in saying whether LCP or CAPE is better in preventing cis-platin-induced lung damage since they obviously possess different mechanisms of action.

Interstitial Cells of Cajal and Neural Structures in the Human Fetal Appendix.

BACKGROUND/AIMS: The interstitial cells of Cajal (ICC) are located within and around the digestive tract's muscle layers. They function as intestinal muscle pacemakers and aid in the modification of enteric neurotransmission. The appendix's unique position requires an appropriate contraction pattern of its muscular wall to adequately evacuate its contents. We investigated the development and distribution of nervous structures and ICC in the human fetal appendix. METHODS: Specimens were exposed to anti-c-kit (CD117) antibodies to investigate ICC differentiation. Enteric plexuses were examined using anti-neuron-specific enolase, and the differentiation of smooth muscle cells was studied with anti-desmin antibodies. RESULTS: During weeks 13-14, numerous myenteric plexus ganglia form an almost uninterrupted sequence throughout the body and apex of the appendix. Fewer ganglia were present at the submucosal border of the circular muscle layer and within this layer. A large number of ganglia appear within the circular and longitudinal muscle layers in a later fetal period. The first ICC subtypes noted were of the myenteric plexus and the submucous plexus. In the later fetal period, the number of intramuscular ICC markedly rises, and this subtype becomes predominant. CONCLUSIONS: The ICC and nervous structure distribution in the human fetal appendix are significantly different from all other parts of the small and large intestine. The organization of ICC and the enteric nervous system provides the basis for the specific contraction pattern of the muscular wall of the appendix.

Prognostic Value and Immunohistochemical Analysis of Mismatch Repair Deficiency in Patients with Stage II and III Colorectal Carcinoma-A Single-Center Study.

Background and objectives: Deficient mismatch repair (MMR) status is associated with good prognosis but poor therapeutic response to adjuvant chemotherapy in patients with colorectal cancer. However, there are some opposed arguments considering therapeutic outcomes in patients with evidenced MMR deficiency in colorectal cancer. The aim of the study was the investigation of prognostic value and immunohistochemical analysis of the MMR-deficiency tumors. Materials and Methods: The study enrolled 104 patients with resected stage II and III colorectal cancer samples from the period 2018-2019. Results: The tumors with deficient MMR status were significantly associated with age up to 50 years and right-sided localization (p < 0.001). During the follow-up period of 22.43 ± 6.66 months, 21 patients (20.2%) died, whereas 14 patients (13.5%) had relapses. The loss of mutL homologue 1/postmeiotic segregation increased 2 (MLH1/PMS2) expression, compared to proficient MMR tumors, was associated with shorter disease-free survival in patients with lymphovascular invasion (p < 0.05), perineural invasion (p < 0.01), stage III (p < 0.05) and high-grade tumor (p < 0.05). Conclusions: This retrospective pilot study of a single-center cohort of patients with stage II and III colorectal cancer highlights the clinical importance of using immunohistochemistry (IHC) analysis as a guide for diagnostic algorithm in a country with limited resources, but with a high prevalence of colorectal carcinoma in the young patients. MMR-deficiency tumors compared with proficient MMR colorectal cancer was not shown to be a significant predictor of disease-free and overall survival.

CD4+ T cell phenotypes in the pathogenesis of immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet counts due to enhanced platelet clearance and compromised production. Traditionally, ITP was regarded a B cell mediated disorder as anti-platelet antibodies are detected in most patients. The very nature of self-antigens, evident processes of isotype switching and the affinity maturation of anti-platelet antibodies indicate that B cells in order to mount anti-platelet immune response require assistance of auto-reactive CD4+ T cells. For a long time, ITP pathogenesis has been exclusively reviewed through the prism of the disturbed balance between Th1 and Th2 subsets of CD4+ T cells, however, more recently new subsets of these cells have been described including Th17, Th9, Th22, T follicular helper and regulatory T cells. In this paper, we review the current understanding of the role and immunological mechanisms by which CD4+ T cells contribute to the pathogenesis of ITP.

Do we really know how to overcome trastuzumab resistance in hormone sensitive metastatic breast cancer?

PURPOSE: This article focuses on how the status of hormone receptors (HR) influences the efficacy of trastuzumab in patients with metastatic HER2-positive breast cancer treated with first-line trastuzumab in combination with taxane-based chemotherapy. METHODS: A prospective study was carried out at the Clinic for Oncology, Clinical Centre in Nis, from January 2015 to until June 2018. A total of 121 patients were treated with first-line trastuzumab in combination with taxane-based chemotherapy. None of the patients from the HR-positive group received hormonotherapy after completion of chemotherapy with trastuzumab. RESULTS: Clinical benefit rate was present in 76% of the patients, including partial response (PR) in 37%, stable disease (SD) in 38%, and complete response (CR) in almost 8% of the patients. Progressive disease (PD) occurred in almost a quarter of the patients, i.e. 24%. Progression-free survival (PFS) in the entire group of patients amounted to 9 months, whereas overall survival (OS) was 30 months. PFS in the HR-negative tumor group was significantly longer (13 months) compared to 8 months in the HR-positive tumor group (p<0.0001; HR 0.49;95% CI 0.31-0.69). Furthermore, OS was significantly longer in the HR-negative tumor group (34 months), compared to 26 months in the HR-positive tumor group (p=0.0073, HR 0.57; 95% CI 0.36-0.90). CONCLUSIONS: These data indicate a different response to anti-HER2 therapy in patients with HER2+ metastatic breast cancer (MBC) according to HR status, thus emphasizing that ER most likely represents an escape pathway for the response to anti-HER2 target therapy and vice versa. Combining hormonotherapy with anti-HER2 therapy surely represents a promising strategy which could help overcome resistance to trastuzumab and other anti-HER2 agents.

Granulocyte-macrophage colony-stimulating factor as a mediator of autoimmunity in multiple sclerosis.

Autoreactive, myelin-specific, CD4+ T cells have a central role in multiple sclerosis (MS) pathogenesis; however the exact phenotype characteristics of these cells remain elusive. Recently, granulocyte-macrophage colony-stimulating factor (GM-CSF) expression has emerged as the main pathological signature of the encephalogenicity in both T and B cell compartment. In this review we have summarized the current data supporting GM-CSF relevance in MS pathophysiology, in the context of both immunomodulatory and neuroinflammatory processes; as well as the potential cellular sources of this stimulating factor, including different T and B cell subsets.

Ten years of using adjuvant trastuzumab in breast cancer in Serbia - Single institution experience.

PURPOSE: The purpose of this study was to determinate disease-free interval (DFI) and overall survival (OS) in HER2-positive breast cancer patients who received adjuvant trastuzumab at the University Clinic of Nis, Serbia, and to investigate the influence of clinicopathological and biological characteristics of the tumor on prognosis. The second aim was to determinate the most frequent cause for the treatment discontinuation, recurrence rate, as well as the site of most common localization of the first recurrence of disease. METHODS: This research was conducted as a retrospective study at the University Oncology Clinic, Clinical Centre in Nis. The study included 238 patients who were operated and treated for HER2-positive breast cancer between January 1st, 2007 to September 30th, 2012 and followed up until December 31st, 2016. Trastuzumab was administered concurrently with taxanes, if administered, or after the completed anthracycline-based chemotherapy. RESULTS: After a median follow up of 69 months the 5-year DFI was 65.9% and 5-year OS was 81.8% and, as expected, significantly longer in the group of patients with smaller tumors, a smaller number of positive axillary lymph nodes, as well as a lower stage of disease (p<0.0001). Patients older than 65 years had a longer DFI compared to the 45-65 and under 45 age groups of patients (p=0.01). No statistical significance was found in the length of DFI in relation to the histological tumor subtype, tumor grade, or the status of hormone receptors. Unlike DFI, a longer OS was recorded in the group of patients with lower tumor grade (p=0.03) and there was no statistically significant difference in survival regarding the age of patients (p=0.07). Recurrence occurred in approximately one third of the patients (38.23%), mostly in the form of local recurrence. Adjuvant therapy with trastuzumab was not completely carried out in 18.49% of the patients, the most common reason being the progression of disease. CONCLUSIONS: A long median follow up period of 69 months indicated that anti-HER2 monoclonal antibody trastuzumab, after anthracycline-based chemotherapy or concurrently with taxanes, is efficient and safe in treating early breast cancer.

Markers of proliferation and cytokeratins in the differential diagnosis of jaw cysts.

We conducted a retrospective study to analyze the histologic and immunohistochemical findings in three main types of odontogenic cyst. We studied 90 archived cystic jaw lesions: 30 dentigerous cysts, 30 keratocystic odontogenic tumors, and 30 radicular cysts. The cyst types were identified on the basis of clinical, radiologic, and histopathologic findings. Immunohistochemical analyses included staining with Ki-67, p53, epidermal growth factor receptor (EGFR), cytokeratin (CK) 8, CK14, CK17, and CK18. Cell immunopositivity was evaluated for the entire epithelium. The criteria for Ki-67 and p53 positivity were dense and/or faint nuclear staining, and cells were considered EGFR-positive if they exhibited membrane staining and/or cytoplasm staining. For the cytokeratins, cells exhibiting cytoplasm staining were considered positive. Five representative fields of each lesion were selected and identified in each of the Ki-67- and p53-stained slides. We found a statistically significant difference in the ratio of Ki-67-positive cells in the entire layer between the keratocystic odontogenic tumors and both the dentigerous cysts and the radicular cysts. A statistically significant difference was observed in the ratio of p53-positive cells between the keratocystic odontogenic tumors and the radicular cysts. Cytokeratins proved to be useful in differentiating radicular cysts from other types of cystic jaw lesions because of their CK8-positive and CK17-negative immunolabeling.

IL-17 signalling in astrocytes promotes glutamate excitotoxicity: Indications for the link between inflammatory and neurodegenerative events in multiple sclerosis.

OBJECTIVE: Th-17 cells have been exclusively referred to inflammatory events in multiple sclerosis (MS), while their importance in the development of glutamate excitotoxicity and the consequent neurodegeneration has been a completely unexplored concept. Accordingly, the objective of our study was to assess IL-17A effect on astrocyte ability to metabolize and release glutamate, considering that astrocytes had the central role in glutamate homeostasis. METHODS: By using primary rat astrocyte cultures, astrocyte ability to uptake glutamate was estimated by the alterations of glutamate transporters (GLAST and GLT-1) expression, whereas changes in glutamine synthetase expression were used to estimate the ability to metabolize glutamate. Gene expression was determined by real time polymerase chain reaction (rtPCR). IL-17A effect on astrocyte ability to produce glutamate was investigated directly, by measuring the level of released glutamate using high performance liquid chromatography (HPLC). RESULTS: Lower concentrations of IL-17A reduced the expressions of both glutamate transporters and glutamine synthetase; however, this effect was lost when IL-17A was applied in a higher dose. IL-17A did not significantly modify glutamate release from astrocyte in basal conditions, but following Ca2+ stimulation, as well as Ca2+ removal from the culture medium, IL-17A stimulated glutamate release in dose-dependent manner. CONCLUSION: Together, these results support that IL-17A could promote glutamate excitotoxicity by decreasing astrocyte ability to uptake and convert glutamate to non-toxic glutamine, but also by stimulating Ca2+ dependent glutamate release. Such interactions between IL-17A and glutamate excitotoxicity implicate the potential link between inflammation and neurodegeneration during MS pathogenesis, and identify astrocytes as a potential target in achieving neuroprotective effects in MS.

The Association of Prenatal Tocolysis and Breastfeeding Duration.

BACKGROUND: To date there are no clinical studies analyzing potential effects of tocolytics on breastfeeding duration in humans. OBJECTIVES: The purpose of this study was to evaluate the association between beta 2 agonists prescribed for tocolysis during pregnancy and breastfeeding duration. METHODS: We conducted a cross-sectional questionnaire study of 114 mothers and filled in the questionnaire developed to directly address the goals of the study. RESULTS: There was a statistically significant difference between breastfeeding duration of mothers who were on tocolytics during pregnancy versus those who were not prescribed tocolytics (9.5 ± 5.7 months versus 4.5 ± 2.1 months) p < 0.001. In addition, hypogalactia was statistically significantly more prevalent in mothers with positive history versus mothers with negative history of tocolytic usage p < 0.001. CONCLUSION: The results of our study indicate that tocolytic treatment in pregnancy is associated with shorter breastfeeding duration and hypogalactia.

Central mucoepidermoid carcinoma of the mandible ­ A case report.

Introduction: Mucoepidermoid carcinoma, compared to other tumors of salivary glands, occurs in 5­10% of cases. Histopathologically, it is divided into a well differentiated tumor that is of low-grade of malignancy, and a medium and poorly differentiated tumor of high grade of malignancy. Central mucoepidermoid carcinoma (CMEC) of the mandible was firstly described by Lepp in 1936, on a 66-year-old female patient. CMEC is characterized by atypical clinical image and radiological manifestation. Case Outline: A 55-year-old female patient was examined at the Clinic of Dentistry in Nis, Serbia, with anamnestic data regarding the presence of painless swelling in the right side of the mandible. Considering the histopathological results and presence of enlarged lymph nodes, right hemimandibulectomy and tumour excision from pterygomandibular space followed by supraomohyoid neck dissection was done. In due course, postoperative radiotherapy was applied (60 Gy) Conclusion: CMEC represents a rare tumor, characterized by local tissue destruction and ability to metastasize. Initial biopsy represented the key in preoperative planing. Radical excision with neck lymph node dissection followed by postoperative radiotherapy in our case represent a successful method of treating CMEC of the mandible.

Deleterious versus protective autoimmunity in multiple sclerosis.

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disorder of central nervous system, in which myelin specific CD4(+) T cells have a central role in orchestrating pathological events involved in disease pathogenesis. There is compelling evidence that Th1, Th9 and Th17 cells, separately or in cooperation, could mediate deleterious autoimmune response in MS. However, the phenotype differences between Th cell subpopulations initially employed in MS pathogenesis are mainly reflected in the different patterns of inflammation introduction, which results in the development of characteristic pathological features (blood-brain barrier disruption, demyelination and neurodegeneration), clinically presented with MS symptoms. Although, autoimmunity was traditionally seen as deleterious, some studies indicated that autoimmunity mediated by Th2 cells and T regulatory cells could be protective by nature. The concept of protective autoimmunity in MS pathogenesis is still poorly understood, but could be of great importance in better understanding of MS immunology and therefore, creating better therapeutic strategies.

Young age and pathological features predict breast cancer outcome - report from a dual Institution experience in Serbia.

PURPOSE: The aim of this study was to investigate the influence of clinicopathological and biological characteristics on prognosis, disease free survival (DFS) and overall survival (OS), of very young patients (≤35 years of age) with breast cancer. METHODS: We retrospectively collected information of 150 women diagnosed with breast cancer, aged ≤35 years, who were operated and treated at two University Hospitals in Serbia between January 2009 and February 2011. RESULTS: After a median follow up of 44 months patients ≤30 had shorter DFS and OS compared to patients aged 31-35 years (p=0.004 and p=0.037, respectively). The differences in DFS and OS were significant with decreased survival associated with higher tumor grade (p=0.005 and p=0.0001, respectively). Tumor size and number of positive nodes were predictors of outcome with decreased survival associated with higher tumor size (p=0.0019 for DFS and p<0.0001 for OS) and increasing number of nodes (p<0.0001 for both). HER 2 receptor did not seem to have a prognostic influence while patients with hormonal receptors (HRs) positive tumors had a better DFS (p=0.034) and OS (p=0.046) than those with HRs negative tumors. In univariate survival analysis, a significant difference in DFS (p=0.0003) and OS (p=0.0003) was found between patients with vs without lymphovascular invasion (LVI). CONCLUSION: Diagnosis of breast cancer at very young age (<30) was associated with increased risk of death and shorter DFS than women aged 31-35. Negative impact on survival was seen in patients with presence of LVI, negative HRs and higher grade and stage at the time of presentation.