High-risk Factor For Development Research Articles

Cytokines secreted from adipose tissues mediate tumor proliferation and metastasis in triple negative breast cancer

BackgroundObesity is a high-risk factor for development and poor prognosis of triple-negative breast cancer (TNBC), which was considered as a high malignant and poor clinical outcome breast cancer subtype. TNBC proliferation and migration regulated by obesity is complex. Here, we studied effects of cytokines secreted from adipose tissue on development of TNBC.MethodsForty postmenopausal cases by Yuebei People’s Hospital of Shaoguan with stage I/IIA TNBC were enrolled. Cytokine concentrations were examined using ELISA analysis. Proliferation and migration of TNBC cell lines were performed using CCK8 assays and Transwell tests. The Log-rank (Mantel-Cox) test, two-tailed Mann-Whitney U test and two-tailed unpaired t test were performed using GraphPad Prism 8.4.2.ResultsSurvival analysis indicated that obese patients with TNBC had worse disease free survival (DFS) as compared with normal weight group (Hazard Ratio 4.393, 95% confidence interval (CI) of ratio 1.071–18.02, p < 0.05). Obese patients with TNBC had severe insulin resistance and high plasma triglycerides. However, plasma adiponectin concentration was decreased and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) concentration was increased in obese TNBC patients as compared with the nonobese group. The similar results were found in the cytokine secretion from adipose tissues and insulin-resistant adipocytes. The secretion of adipose tissue from obese TNBC patients could promote proliferation and migration of TNBC cell lines, including MDA-MB-157, MDA-MB-231, MDA-MB-453 and HCC38 cells. These TNBC cell lines co-incubated with insulin-resistant 3T3-L1 adipocytes or supplementing these cytokines medium also exhibited increase of proliferative and migratory capacity.ConclusionTNBC patients with obesity had worse prognosis compared with the normal weight groups. Alteration of cytokines secreted from adipose tissues mediated proliferation and migration of TNBC, leading to tumor progression in TNBC patients with obesity.

348. Characteristics and Outcomes in Hospitalized Patients with Covid-19 Complicated by Fungemia: A Single Center Retrospective Study

BackgroundCovid19 caused by SARS-CoV2 can lead to significant morbidity and mortality. Fungemia is a rare hospital-associated infection and there are limited data regarding its association with Covid19. We reviewed all cases of fungemia in our Covid19 cohort at Stony Brook University Hospital (SBUH). MethodsWe conducted a retrospective medical record review of patients admitted with Covid19 in a 3-month interval. We reviewed positive blood cultures for fungi and recorded co-morbidities, co-infections, length of stay, treatments, and outcomes (survival vs death). There were 60 positive blood cultures for fungi in 25 unique patients (Table 1); in prior years < 30 per year reported at SBUH.Table 1. Fungal Blood Cultures Collation of each unique identified fungal species from fungal blood cultures in patients hospitalized with Covid-19ResultsDuring a 3 month interval at the local peak of the pandemic 1398 patients hospitalized with Covid19 at SBUH, 25 cases of fungemia were detected; C. albicans (CA) n=8,32%, non C albicans species (nCA) n=16,64%, and C. neoformans n=1,4%, 17/25 (68%) also with bacteremia during same hospitalization. In same 3 months there were 264 cases of bacteremia and Covid19 co-infection. Demographics and medical co-morbidities of fungemic patients are in Table 2. Majority were men (76%). No difference between fungaemic (FC) and total cohort (TC) in median age (62 vs 62), DM p=0.31, HTN p=1.0, COPD p=0.12. Within FC, DM was higher in nCA group (58.8%) vs CA group (37%). Mortality was 40% in FC vs 15% in TC, p< 0.001. Within FC mortality was 56% in nCA and 25% in CA group. C. parapsilosis was the most common nCA species isolated with 43% mortality. FC more likely to require ICU and mechanical ventilation (88% vs 15%, p< 0.0001) and had longer median length of stay 42 days vs 22 days. The median time from admission to fungaemia was 21d, from central line placement 19d, Table 3. Of FC 21 (84%) were treated with steroids/Tocilizumab concurrently. Of note, no mortality was recorded in the 4 patients that did not receive steroids/Tocilizumab. PCT and WBC were significantly higher at time of fungemia as compared to admission, Table 3. Table 2, Patient co-morbidities and hospitalization stay characteristics Co-morbidities and requirement for ICU stay, mechanical ventilation for total cohort Covid-19 and fungemic cohortTable 3, Patient Characteristics and Laboratory Parameters Relevant patient characteristics and laboratory parameters in patients hospitalized with Covid19 and fungemiaConclusionFungemia in hospitalized patients with COVID-19 is associated with higher mortality. We observed higher fatality in non C. albicans infections. Prolonged use of central line catheters and concurrent treatment with steroids/tociluzimab are likely high-risk factors for development of fungemia. Disclosures All Authors: No reported disclosures

Prevalence of obesity and it’s associated risk factors among policemen of Chitradurga district, Karnataka, India

Background: Obesity is an increasingly prevalent disease worldwide and can be regarded as a health problem among individuals of different occupations, including policemen, who are responsible for public security. Working throughout the day in stressful atmosphere produces adverse physical and psychological effects. We conducted this study to find the prevalence of obesity among policemen, if any, and to identify the associated risk factors for obesity in this population.Methods: Cross sectional study was conducted among 410 police personnel of 4 talukas of Chitradurga District, Karnataka from July 2017 to January 2018. Semi-structured questionnaire was prepared to collect the data, which consist of socio-demographic data, clinical examination findings, anthropometric measurements and biochemical investigations. At the end whoever had high risk factors, were treated for the same along with advice on healthy life style. Data entered in Microsoft Excel 2007 and analysed using SPSS software, version 20. Frequency tables, ANOVA test and chi-square test were used for analysis and interpretation.Results: There were total 392 males and 18 females. Age group was ranging from 21 years to 59 years. 201(49%) of the police officers were overweight and 45(11%) were obese. Ideal weight police men were younger than obese policemen and weighed less than obese police. There was statistical difference in BMI between the three groups of policemen. The mean TG and TC levels among overweight and obese were higher than ideal weight policemen and this difference was statistically significant. 32.9% of participants had a high TC level (≥200 mg/100 ml). Moreover, 93.4% and 84.1% had a low level of HDL-C and high level of LDL-C, respectively (&lt;40 mg/ 100 ml and &gt;150 mg/100 ml, respectively). 49.5% of our study participants had TG levels &gt;150mg/100 ml. 60.5% and 42.7% had high SBP and DBP, respectively (&gt;130 mmHg and &gt;90mmHg). The difference between TC and HDL between different BMI groups was statistically significant.Conclusions: Obesity and hypertension are high risk factors for development of cardiovascular diseases. Early detection of the same and effective implementation of a physical fitness program, a regular balanced diet, inoculation training for managing stress can improve the life of police personnel.

Association analysis of IL-4 VNTR polymorphism with rheumatoid arthritis in Iranian patients

Rheumatoid arthritis (RA) is an autoimmune disease characterized by movement disability and pain in the joints. The affected individuals are susceptible to other subsequent diseases, exacerbating the condition. To find out the genetic variability of this disease at the genomic level for the first time in the Iranian population, we carried out an investigation on the VNTR of IL-4 gene within its third intron. For this goal we isolated the genomic DNA from blood samples of 576 rheumatoid arthritis patients and 546 healthy controls and investigated the presence or absence of specific amplicons via polymerase chain reaction (PCR). The size of each amplicon on a 1.5% agarose gel corresponded to a certain number of tandem repeats which indicated a specific allele. Statistical test of χ2 Fisher’s exact test and odds ratio (OR) was used to analyze the data. The results showed that RA1/RA1 genotype was the dominant genotype in both healthy controls and patients and the heterozygote genotype of RA1/RA2 was observed more in the healthy controls than patients (108 vs. 66) with significant difference with P value < 0.005 and odds ratio of 0.214. However two genotypes of RA2/RA2 and RA2/RA3 were exclusively observed in the patients’ samples with P value = 0.023 and odds ratio of 0.988. We concluded that IL-4 VNTR polymorphism has a strong association with rheumatoid arthritis and might be a high risk factor for development of rheumatoid arthritis in the investigated Iranian population.

Association Analysis of IL-4 VNTR Polymorphism with Rheumatoid Arthritis in Iranian Patients

Rheumatoid arthritis (RA) is an autoimmune disease characterized by movement disability and pain in the joints. The affected individuals are susceptible to other subsequent diseases, exacerbating the condition. To find out the genetic variability of this disease at the genomic level for the first time in the Iranian population, we carried out an investigation on the VNTR of IL-4 gene within its third intron. For this goal we isolated the genomic DNA from blood samples of 576 rheumatoid arthritis patients and 546 healthy controls and investigated the presence or absence of specific amplicons via polymerase chain reaction (PCR). The size of each amplicon on a 1.5% agarose gel corresponded to a certain number of tandem repeats which indicated a specific allele. Statistical test of χ2 Fisher’s exact test and odds ratio (OR) was used to analyze the data. The results showed that RA1/RA1 genotype was the dominant genotype in both healthy controls and patients and the heterozygote genotype of RA1/RA2 was observed more in the healthy controls than patients (108 vs. 66) with significant difference with P value < 0.005 and odds ratio of 0.214. However two genotypes of RA2/RA2 and RA2/RA3 were exclusively observed in the patients’ samples with P value = 0.023 and odds ratio of 0.988. We concluded that IL-4 VNTR polymorphism has a strong association with rheumatoid arthritis and might be a high risk factor for development of rheumatoid arthritis in the investigated Iranian population.

Dental fear and premature tooth extraction

Dental avoidance is a high risk factor for development of odontophobia and poor oral health including premature tooth extraction in children. The aim of this study is to evaluate the connection between the dental fear and premature tooth loss. Subject of monitoring of the clinical research were 140 school children with mixed dentition. The clinical group consists of 90 children with prematurely extracted teeth. The patients from the clinical group were divided into three groups of 30 patients. The control group consists of 50 children with intact denture. А special questionnaire was filled from the parents of the examined children about the dental fear of their children, whether there is such a fear or not. The results show that while in the control group the majority of children are not afraid of dental treatment – 79,2%, then in groups surveyed more than half of the children said they are afraid of dental treatment, especially the third group – 57,7%. Conclusion: The children with prematurely extracted teeth have a higher level of dental anxiety due to which they are with poor dental health and early tooth loss. The use of behavioural techniques are recommended in order to improve their oral health.

Allergic Reactions and Nickel-Free Braces: A Review

Nickel is a constituent of many dental alloys. The aim of this review is to assess the most common allergic reactions reported in orthodontics related to nickel and the use of nickel free braces. A computerized literature search was conducted in PubMed for articles published on allergy in relation to orthodontics and nickel free braces. The MeSH term used was allergy, nickel free braces and orthodontics. Level of nickel in saliva and serum increases significantly after the insertion of fixed orthodontic appliances. Some nickel compounds, which are mildly cytotoxic, have been implicated as carcinogens by inhalation in industrial settings, but these compounds are not present in dental related operations. Studies have implicated allergy in the etiology of hypodontia. It has also been considered as a high risk factor for development of extensive root resorption during the course of orthodontic treatment. This review discusses the relationship and implications of allergy in orthodontics. Nickel-free braces (Ni content - 2% max.) seem to represent a viable alternative for orthodontic patients who are allergic to nickel. However, further in vivo studies, considering the immunology characteristics of patients, are needed to determine the clinical implications of the findings of this study.

Pretreatment screening on distant metastases and head and neck cancer patients: Validation of risk factors and influence on survival

Previously identified high risk factors for development of distant metastases are: three or more lymph node metastases, bilateral lymph node metastases, lymph nodes larger than 6cm, low jugular lymph node metastases, locoregional tumor recurrence and second primary tumors. The aims of this study were to validate these specific risk factors and to investigate the impact of time (i.e. during screening or follow-up) of detection of distant metastases on survival. From a total of 301 HNSCC patients with high risk factors who were scheduled for extensive treatment and underwent pretreatment screening on distant metastases using chest CT and/or whole body PET(-CT) (in some patients combined with whole body MRI), the high risk factors, the development and time point of distant metastases and survival were analyzed. Forty-four percent developed distant metastases. Multivariate analysis revealed that bilateral lymph node metastases is the strongest predictive factor. Locoregional recurrence and second primary tumor were the risk factors associated with the lowest cumulative incidence. However, if the risk factor locoregional recurrence was split into local and regional recurrences, regional recurrence became a high risk factor. The more high risk factors a patient had the lower the 5-year distant metastases free survival was. Patients with distant metastases detected pretreatment has a significant worse survival (corrected for lead time bias) compared to patients with distant metastases diagnosed during follow-up. The validity of three or more lymph node metastases, bilateral lymph node metastases, lymph nodes larger than 6cm, low jugular lymph node metastases and regional recurrence as high risk factors for the development of distant metastases was confirmed. If more high risk factors are present the cumulative incidence of distant metastases increases significantly. The detection of distant metastases by pretreatment screening worsens the overall survival as compared to distant metastases detected during follow-up.

New 'multi-omics' approach and its contribution to hepatocellular carcinoma in China.

Hepatocellular carcinoma (HCC) is one of the most common liver neoplasms worldwide, and 70-80% cases are accounted in Asian countries (1). Etiological background of HCC patients is different in each country or area. In China, infection of hepatitis B virus (HBV) is a main etiological factor of increased incidence of HCC. In fact, 93 million HBV carriers are Chinese, accounting for 2/3 of such patients worldwide, and about 20 million of these people have chronic HBV infection (2). Chronic HBV infection is a high risk factor for development of HCC. Therefore, the follow-up of those chronic viral hepatitis type B patients and the early-detection of HCC in those patients are pressing tasks to reduce the incidence of HCC in China (3).

Graft-versus-host disease after solid organ transplantation: A single center experience and review of literature

Graft-versus-host disease (GVHD) is an uncommon cause of morbidity and mortality after solid organ transplantation that is most likely under-diagnosed. We describe our single center experience with three cases of GVHD diagnosed over a period of 15 years in a total of 2,271 solid organ transplant recipients. We describe three case reports: (1) a 3-week old neonate who developed GVHD 16 months after living-related liver transplant, (2) a 14-year old adolescent who developed GVHD 4 months following an unrelated cadaveric pancreas transplant and; (3) a 27-year old male who developed GVHD 18 days after simultaneous kidney-pancreas transplant from an unrelated donor. GVHD was confirmed through skin biopsies, engraftment profile from bone marrow biopsy and variable number tandem repeat analysis. Treatment strategies included use of corticosteroids and sirolimus monotherapy, corticosteroids and mesenchymal stromal cell therapy and reduction of immunosuppression. We observed that African-American race, sexual and HLA mismatching and cytomegalovirus infection may be high risk factors for development of GVHD following solid organ transplant. GVHD continues to be a rare but fatal complication following solid organ transplantation that demands a high index of clinical suspicion for diagnosis and management. Future approaches may focus on early recognition of risk factors and improving treatment protocols using a combination of mesenchymal stromal cell transplantation with pharmacotherapy.

Neoplasia intraepitelial vulvar: um problema atual

Vulvar intraepithelial neoplasia (VIN) is a pathological denomination coined by the International Society for Study of Vulvo-vaginal Diseases (ISSVD) and adopted by the International Society of Gynaecological Pathology (ISGYP) and by the World Health Organization. VIN is a heterogeneous pathological entity with a usual type (warty, basaloid and mixed) and a differentiated type. The incidence of the disease is increasing, especially in young women. The high-risk human papillomavirus (HR-HPV) infection, human immunodeficiency virus (HIV) infection, smoking, cervical, vaginal and rectal intraepithelial neoplasia are considered to be high risk factors for development of VIN. There are no specific symptoms or vulvar macroscopic aspects of VIN. However, a clinical lesion is always present. Liberal vulvar biopsies under colposcopy guidance should be done. Patients with diagnosis of VIN harbor an increased risk for vulvar invasive cancer. Surgical excision and laser CO2 vaporization are the most popular therapeutic modalities for VIN treatment, both with high rates of recurrence. A close follow-up of the patients is advised. Topical imiquimod seems to be a promising treatment option. Probably, prophylactic vaccination against HR-HPV will be an important tool for VIN prevention.

Compositional Protein Analysis of High Density Lipoproteins in Hypercholesterolemia by Shotgun LC-MS/MS and Probabilistic Peptide Scoring

A protein of a biological sample is usually quantified by immunological techniques based on antibodies. Mass spectrometry offers alternative approaches that are not dependent on antibody affinity and avidity, protein isoforms, quaternary structures, or steric hindrance of antibody-antigen recognition in case of multiprotein complexes. One approach is the use of stable isotope-labeled internal standards; another is the direct exploitation of mass spectrometric signals recorded by LC-MS/MS analysis of protein digests. Here we assessed the peptide match score summation index based on probabilistic peptide scores calculated by the PHENYX protein identification engine for absolute protein quantification in accordance with the protein abundance index as proposed by Mann and co-workers (Rappsilber, J., Ryder, U., Lamond, A. I., and Mann, M. (2002) Large-scale proteomic analysis of the human spliceosome. Genome Res. 12, 1231-1245). Using synthetic protein mixtures, we demonstrated that this approach works well, although proteins can have different response factors. Applied to high density lipoproteins (HDLs), this new approach compared favorably to alternative protein quantitation methods like UV detection of protein peaks separated by capillary electrophoresis or quantitation of protein spots on SDS-PAGE. We compared the protein composition of a well defined HDL density class isolated from plasma of seven hypercholesterolemia subjects having low or high HDL cholesterol with HDL from nine normolipidemia subjects. The quantitative protein patterns distinguished individuals according to the corresponding concentration and distribution of cholesterol from serum lipid measurements of the same samples and revealed that hypercholesterolemia in unrelated individuals is the result of different deficiencies. The presented approach is complementary to HDL lipid analysis; does not rely on complicated sample treatment, e.g. chemical reactions, or antibodies; and can be used for projective clinical studies of larger patient groups.