Epigenetic and Molecular Alterations in Obesity: Linking CRP and DNA Methylation to Systemic Inflammation.

Obesity is marked by excessive fat accumulation in the adipose tissue, which disrupts metabolic processes and causes chronic systemic inflammation. Commonly, body mass index (BMI) is used to assess obesity-related risks, predicting potential metabolic disorders. However, for a better clustering of obese patients, we must consider molecular and epigenetic changes which may be responsible for inflammation and metabolic changes. Our study involved two groups of patients, obese and healthy donors, on which routine analysis were performed, focused on BMI, leukocytes count, and C-reactive protein (CRP) and completed with global DNA methylation and gene expression analysis for genes involved in inflammation and adipogenesis. Our results indicate that obese patients exhibited elevated leukocytes levels, along with increased BMI and CRP. The obese group revealed a global hypomethylation and upregulation of proinflammatory genes, with adipogenesis genes following the same trend of being overexpressed. The study confirms that obesity is linked to systematic inflammation and metabolic dysfunction through epigenetic and molecular alterations. The CRP was correlated with the hypomethylation status in obese patients, and this fact may contribute to a better understanding of the roles of specific genes in adipogenesis and inflammation, leading to a better personalized therapy.

Cyanoacrylate Adhesives Used for Topical Hemostasis A Systematic Review.

Introduction: In this systematic review the topical hemostatic properties of Cyanoacrylate Adhesives (CA) have been studied. Material and Method: Four major scientific databases (Embase, Scopus, PubMed, and Web of Science) were inquired, retrieving reviews and meta-analysis studies, clinical trials, experimental studies, and case reports that presented data regarding topical hemostasis and CA. English written articles, published in the last 10 years were collected. The last search was performed on the 1st of August 2023. Risk of bias in the included studies was assessed using study-design specific, evidence-based tools. Results: A summary focused on relevant information of all included studies was drafted and the results of the studies have been synthetized and compared. A total of 42 studies have been included in the review (14 reviews and meta-analysis, 11 clinical trials, 9 experimental studies and 8 case reports). CA exhibited important topical hemostatic capabilities, comparable with other performant hemostatic materials. Although most included studies concluded that CA were potent topical hemostatic agents, the high level of heterogeneity among the studies prevented us from performing a meta-analysis. Conclusion: The results of this review show that CA-based compounds represent an important line of research towards the perfect hemostatic material.

Absolute and Functional Iron Deficiency in Colon Cancer: A Cohort Study.

Background and Objectives: Iron is an essential micronutrient for many biological functions and has been found to be intimately linked to cancer biology. Although the effects of increased dietary iron consumption in the development of CRC have been previously investigated in several cohort studies, the available evidence on the involvement of iron deficiency in this process is relatively scarce. Previously published papers did not analyze specific outcomes, such as the presence of biologically aggressive histopathological characteristics, that are associated with the subtypes of iron deficiency. The purpose of this study was to investigate the connection between the development of colorectal cancer and the presence of functional iron deficiency (FID), which is defined as insufficient biological availability of iron in the presence of adequate storage reserves, or absolute iron deficiency (AID), which is defined as severely depleted iron storage levels. Materials and Methods: Our paper represents a single center registry-based cohort study. Iron levels were routinely evaluated upon diagnosis of CRC and the collected data were coupled with patient- and tumor-specific data (2018-2022). Spearman's correlation coefficient and the chi-squared test were used to analyze the association. Results: Out of 129 patients, 75 (58.13%) were anemic. AID was identified in 26.35% of cases and FID was encountered in 51.16% of cases. A statistically significant association between FID and lymphatic invasion was encountered. An analysis of the correlation demonstrated a significant association between anemia and right-sided tumor location. Conclusions: Functional iron deficiency seems to be independently associated with lymphatic invasion. Although a statistically significant correlation with the T or N stage was not demonstrated, the analysis suggested a potential positive relationship between the presence of FID and more aggressive tumor characteristics.

Silicone Adenopathy and Intractable Axilary Pain after Breast Implant Augmentation - Case Report.

Introduction: Silicone lymphadenophaty (siliconoma) is a rare complication secondary to breast implant augmentation or breast reconstruction surgery. Although it is usually linked to the age of the implant, the predominant etiology is multifactorial. Herein, we report a case of extensive siliconoma in the axilla in the hope that our experience will contribute to clinical decision making. Case presentation: We report the case of a 41-year-old woman with intense pain in her right axilla 20 years after breast augmentation surgery. Analgesics were of limited use and the pain became debilitating over time. After a thorough physical examination, imaging studies found three central axillary lymph nodes with a "snowstorm" appearance, suggestive of silicone lymphadenopathy. A complete excision of the lessions was performed with resolution of pain on follow-up. Subsequent histological analysis showed lymph nodes containing large doplets of silicone. Conclusions: General and plastic surgeons must remain aware as silicone adenopathy can be causative of anxiety and significant local symptoms among patients. Thorough investigations are needed in order to exclude malignancies and provide an optimal treatment strategy.

Adverse Outcome of Two-Staged Breast Reconstruction: More Than One Culprit.

BACKGROUND: Two-stage prosthetic breast reconstruction with initial insertion of a tissue expander followed by change-over to an implant after a period of inflation has become a well-established option in breast reconstruction. Our aim was to analyze the feasibility of two-stage breast reconstruction in our center by following the surgical technique, number of complications and associated risk factors. PATIENTS AND METHODS: We studied 91 patients who underwent skin sparring mastectomy and tissue expander placement in our surgical unit, between January 2017 and December 2021. Axillary surgery was performed in all patients. We collected data on age, smoker status, breast size, comorbidities, tumor characteristics, neoadjuvant treatment and surgical intervention details. RESULTS: Skin necrosis (12.08%) and seroma (16.48%) were the most common complications. 7.69% of the patients required reintervention. Patients underwent delayed reconstruction after more than 6 months in 69.7% of the cases, while the overall reconstruction rate was 86.08%. Smoker status, an increased body mass index, comorbidities, neoadjuvant treatment, type of incision and location of the implant were the main factors that led to adverse outcomes. CONCLUSIONS: Tissue expanders are a viable option for reconstruction; however, we observed a higher incidence of skin complications in smokers and in cases where periareolar incision was used.

Feasibility of oncoplastic surgery in breast cancer patients with associated in situ carcinoma.

PURPOSE: Wide surgical margins are needed in order to treat locally the in situ ductal carcinoma of the breast. Breast conserving surgery using oncoplastic techniques in treating in situ ductal carcinoma can be a good option improving cosmetic and pathological outcome. METHODS: Between January 2019 and July 2019, 76 patients with invasive carcinoma associated with in situ ductal carcinoma were eligible for breast conserving surgery and were admitted to Cluj-Napoca First Surgical Clinic. Patients were divided into two groups, one group with simple lumpectomy and the other group with oncoplastic procedure. RESULTS: 26 patients had oncoplastic surgery while 47 patients underwent simple lumpectomy. Lateral mammoplasty was the most frequent oncoplastic procedure (41.3%). Mean tumor size was 3.19 cm (SD 0.76) in the oncoplastic cohort while in the simple lumpectomy cohort the mean tumor size was 1.20 cm (SD 0.89). Regarding tumor size, better surgical resection margins were obtained using oncoplastic procedure (p=0.051). No difference between groups in terms of perioperative complications was observed (p=0.32). CONCLUSIONS: Breast conserving surgery with oncoplastic techniques are oncologically safe, obtaining better surgical margins in ductal carcinoma in situ.

Preventing Breast Cancer-Related Lymphedema: Feasibility of Axillary Reverse Mapping Technique.

INTRODUCTION: Our study aimed to determine the feasibility of axillary reverse mapping (ARM) technique, the identification rate of ARM nodes and their metastatic involvement, as well as to identify the factors that influence the identification and metastatic involvement. MATERIAL AND METHODS: In total, 30 breast cancer patients scheduled for axillary lymph node dissection were enrolled in our study. The lymphatic nodes that drain the arm were identified by injecting 1 mL of blue dye in the ipsilateral upper arm; then, the ARM nodes were resected along with the other lymph nodes and sent for histological evaluation. RESULTS: Identification of ARM node was successful in 18 patients (60%) and 22.22% of the identified ARM lymph nodes had metastatic involvement. Patients with identified ARM nodes had a significant lower BMI and a statistically significant relationship between axillary lymph node status and ARM node metastases was proven. Most of ARM lymph nodes (96.3%) were found above the intercostobrachial nerve, under the axillary vein and lateral to the thoracodorsal bundle. CONCLUSIONS: The ARM procedure is easy to reproduce but might not be appropriate for patients with a high BMI. The rate of metastatic involvement of ARM nodes is significant and no factor can predict it, showing that the preservation of these nodes cannot be considered.

Genetic and epigenetic mechanisms involved in bariatric surgery.

Morbid obesity (BMI>40 kg/m2) is a challenging health condition with an increasing incidence in the last decades. Conventional therapy which consists in diet and lifestyle interventions, along with pharmaceutical therapy, has a limited effect on morbidly obese patients. In this context, bariatric surgery is the most effective approach, leading to significant weight loss, along with other beneficial effects like type 2 diabetes resolution or improvement of cardiovascular status. The bariatric surgery outcomes can widely vary among individuals, with a significant percentage of patients having small benefits from the operation. These variations may be partially explained by the genetic background of each individual. During the last years, several studies have been conducted in order to determine the genetic and epigenetic factors involved in bariatric surgery outcomes. Many genes involved in different molecular pathways were found to be associated with weight loss after bariatric surgery. Epigenetic studies revealed that genes methylation may be influenced by weight loss interventions. All these findings suggest that there is an intimate connection between genetic and epigenetic factors and the bariatric surgery outcomes. Further studies are required in order to better understand if genetics can be used in order to predict the operation results. KEY WORDS: Bariatric surgery, Body-mass index, Epigenetic, Genetic.

Multilayered Porous Titanium-Based 3rd Generation Biomaterial Designed for Endosseous Implants.

This work proposes a novel complex multi-layered material consisting of porous titanium as a substrate and a complex coating consisting of a chitosan film engulfing microsphere loaded with growth factors such as BMP2 (bone morphogenic protein 2) and IGF1 (insulin-like growth factor-1). The microspheres were obtained through deposition of dual layers of calcium cross linked pectin-chitosan/pectin polyelectrolyte onto a BSA (bovine serum albumin) gel core. The multilayer was conceived to behave like a 3rd generation biomaterial, by slow delivery of viable growth factors around implants, and to assist the healing of implantation wound and the development of new vital bone. The biologic effect of the delivery of growth factors was studied in vitro, on MSC-CD1 mesenchymal stem cells, and in vivo, on CD1 mice. Proliferation and differentiation of cells were accelerated by growth factors, especially IGF1 for proliferation and BMP2 for differentiation. In vivo tests analyzed histologically and by MicroCT show a more structured tissue around BMP2 samples. The present concept will give the best clinical results if both growth factors are delivered together by a coating film that contains a double population of microcarriers.

Neutrophils-to-lymphocytes, lymphocytes to-monocytes and platelets-to-lymphocytes ratios - predictive biomarkers for response to neoadjuvant chemotherapy in breast cancer.

PURPOSE: Several biomarkers have been reported to correlate with neoadjuvant chemotherapy response. Our aim was to establish the correlation between neutrophils-to-lymphocytes (NLR), lymphocytes-to-monocytes (LMR), and platelets-to-lymphocytes ratios (PLR) and the Miller Payne grade (MPG) and Residual Cancer Burden Score (RCB), as indicators to response to chemotherapy. METHODS: Data were retrospectively collected from the First Surgical Clinic database between January 2016 and December 2018. RESULTS: 96 patients were included in the study. The multivariate regression analysis showed a statistical correlation between oestrogen (ER) and progesterone receptor (PR) status, Ki67 over 15%, and tumour infiltrating lymphocytes (TILs) and MPG and RCB. For the three studied ratios, p value was statistical not significative. ROC curve showed a cut-off value of 2.7 NLR, for which correlation with the pathological complete response to chemotherapy (pCR) was significative (p=0.03). CONCLUSIONS: Our findings suggest that NLR can be a predictive biomarker for pCR. Further studies, on larger sample size, are necessary to establish the correlation with MPG and RCB.

Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?

The status of axillary lymph nodes is an important prognostic factor in the outcome of breast cancer tumors. New trials changed the attitude towards axillary clearance. In the era of development of new immune therapies for breast cancer, it is important to identify a biomarker that can predict lymph node status. Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. Although the correlation between TILs and response to chemotherapy was established by previous studies, our retrospective study investigated the correlation between TILs and lymph node status. We analyzed data on 172 patients. According to stage, patients were divided in two groups: patients who underwent primary surgical treatment (breast-conserving or mastectomy and sentinel lymph node (SLN) biopsy +/- axillary clearance in conformity with lymph node status) and patients who received chemotherapy prior to surgical treatment (breast-conserving or mastectomy + axillary clearance). We showed a good inverse correlation between TILs and lymph nodes status for both early stage and locally advanced breast cancers. Moreover, TILs are a predictor for positive lymph nodes in the axilla in patients undergoing axillary clearance after SLN biopsy, with no statistical difference between the intrinsic or histological subtype of breast cancers. We also obtained a significant correlation between TILs and response to chemotherapy with no significative difference according to histological subtype. Although further data have still to be gathered before meeting the criteria for clinical utility, this study demonstrates that TILs are one of the most accredited forthcoming biomarkers for breast cancer (BC) patients.

Operator-related risk factors of anastomotic leaks after colorectal surgery: an up-to-date.

Digestive fistulas are a major complication after digestive surgery. Anastomotic leakage increases the hospitalization time, the prognosis and survival rate after colorectal surgical interventions. The factors involved are either systemic (determined by the patients' co-morbidities), or local (vicious surgical technique or the injuries produced by the disease that requires the anastomosis). Although there are many studies regarding the risk factors of anastomotic leaks, there is no consensus for the role played by each one of them in the healing process of digestive sutures. Most authors sustain that the importance of systemic factors is secondary, the main role being played by the surgeon and the local conditions of the anastomosis. Knowledge of the risk factors can lead to new methods of reducing the incidence of anastomotic leaks by improving vascularization, limiting the tension and the duration of surgery, and by new surgical techniques used for digestive sutures.

Expression of TLR4 protein is reduced in chronic renal failure: evidence from an experimental model of nephron reduction.

Toll-like receptor 4 (TLR4) signaling is involved in various acute and chronic renal lesions and contributes to inflammation and fibrosis in several organs; the latter are important determinants to the progression of chronic kidney disease (CKD). We aimed to assess TLR4 expression in progressive CKD and relate it to severity of kidney damage, using an experimental nephron reduction model. Male Wistar rats were subjected to subtotal nephrectomy using the ligation technique, after 12 weeks of observation, serum creatinine and proteinuria were determined, animals were sacrificed, glomerulosclerosis and interstitial scarring were quantified histologically, and TLR4 expression was assessed by immunohistochemistry. Sham-operated rats served as controls. Case animals had significantly higher creatinine, proteinuria, glomerulosclerosis and tubulointerstitial involvement. TLR4 expression was prominent in proximal tubes, less staining was observed on infiltrating inflammatory cells. Percentage of TLR4-positive tubes was reduced in the subtotal nephrectomy animals, when compared to controls (0.67±0.09 versus 0.79±0.07, p=0.003). Percentage of TLR4-positive tubes correlated inversely to markers of kidney damage: to proteinuria (r=-0.55, p=0.02), serum creatinine (r=-0.53, p=0.01); percentage of glomeruli with glomerulosclerosis (r=-0.54, p=0.01) and tubulointerstitial score (r=-0.36, p=0.01). As TLR4 staining appears in tubular casts only in nephrectomy animals, shedding from damaged tubular cells is a very likely explanation for the reduced TLR4 expression in the kidneys of subjects with experimental nephron reduction.