Harnessing Metformin's Immunomodulatory Effects on Immune Cells to Combat Breast Cancer.

Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin's impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ+ NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1+, FoxP3+, and IL-10+ NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46+ NKT cells and increased FasL expression, while lowering the percentages of FoxP3+, PD-1+, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10+ and FoxP3+ Tregs, along with Gr-1+ myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10+ and FoxP3+ Tregs, Gr-1+, NF-κB+, and iNOS+ MDSCs, and iNOS+ dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin's broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types.

Development of FluoAHRL: A Novel Synthetic Fluorescent Compound That Activates AHR and Potentiates Anti-Inflammatory T Regulatory Cells.

Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.

Comprehensive Evaluation of Quality of Life following Upper Eyelid Blepharoplasty: A Prospective Analysis.

Background and Objectives: Upper eyelid blepharoplasty is a surgical procedure that addresses both aesthetic and functional concerns, offering transformative potential for patients' overall well-being. This study systematically evaluates the comprehensive impact of upper eyelid blepharoplasty on patients' quality of life, employing rigorous methodologies and standardized assessment protocols. Materials and Methods: A prospective, randomized controlled trial was conducted, involving 348 patients aged 49 to 87 years. Patients were randomly assigned to receive either continuous or intradermal sutures following upper eyelid surgery. Validated FACE-Q questionnaires were used to assess various outcomes, including early-life impact, expectations, satisfaction with eyes, overall face satisfaction, satisfaction with the outcome, psychological function, social function, and adverse effects. Results: Results indicate significant improvements in multiple domains of patient-reported outcomes following upper eyelid blepharoplasty, including satisfaction with eyes, overall face satisfaction, satisfaction with the outcome, psychological function, and social function. Notably, no significant differences were observed between suturing techniques regarding patient satisfaction and well-being. Adverse effects were minimal and improved over time. Conclusions: The study underscores the transformative nature of upper eyelid blepharoplasty in enhancing patients' quality of life, addressing both cosmetic and functional concerns. Utilizing standardized assessment tools like the FACE-Q questionnaire facilitates a comprehensive understanding of treatment outcomes and enables patient-centered care. Overall, this research contributes to the growing evidence supporting the positive impact of upper eyelid blepharoplasty on patients' well-being, emphasizing the importance of continued research and standardized assessment protocols in advancing patient care in cosmetic surgery.

Increased Pro Th1 And Th17 Transcriptional Activity In Patients With Severe COVID-19.

Background: COVID-19 is known to disrupt immune response and induce hyperinflammation that could potentially induce fatal outcome of the disease. Until now, it is known that interplay among cytokines is rather important for clinical presentation and outcome of COVID-19. The aim of this study was to determine transcriptional activity and functional phenotype of T cells and the relationship between pro- and anti-inflammatory cytokines and clinical parameters of COVID-19 severity. Methods: All recruited patients met criteria for COVID-19 are were divided in four groups according to disease severity. Serum levels of IL-12, IFN-γ, IL-17 and IL-23 were measured, and flow cytometry analysis of T cells from peripheral blood was performed. Results: Significant elevation of IL-12, IFN-γ, IL-17 and IL-23 in stage IV of the disease has been revealed. Further, strong intercorrelation between IL-12, IFN-γ, IL-17 and IL-23 was also found in stage IV of the disease, marking augmented Th1 and Th17 response. Analyses of T cells subsets indicate a noticeable phenotype change. CD4+, but not CD8+ T cells expressed increased transcriptional activity through increased expression of Tbet and RORγT, accompanied with increased percentage of IFN-γ and IL-17 producing T cells. Conclusion: Our results pose a novel hypothesis of the underlying mechanism behind deteriorating immune response in severe cases of COVID-19.

Gray-Level Co-occurrence Matrix Analysis of Nuclear Textural Patterns in Laryngeal Squamous Cell Carcinoma: Focus on Artificial Intelligence Methods.

Gray-level co-occurrence matrix (GLCM) and discrete wavelet transform (DWT) analyses are two contemporary computational methods that can identify discrete changes in cell and tissue textural features. Previous research has indicated that these methods may be applicable in the pathology for identification and classification of various types of cancers. In this study, we present findings that squamous epithelial cells in laryngeal carcinoma, which appear morphologically intact during conventional pathohistological evaluation, have distinct nuclear GLCM and DWT features. The average values of nuclear GLCM indicators of these cells, such as angular second moment, inverse difference moment, and textural contrast, substantially differ when compared to those in noncancerous tissue. In this work, we also propose machine learning models based on random forests and support vector machine that can be successfully trained to separate the cells using GLCM and DWT quantifiers as input data. We show that, based on a limited cell sample, these models have relatively good classification accuracy and discriminatory power, which makes them suitable candidates for future development of AI-based sensors potentially applicable in laryngeal carcinoma diagnostic protocols.

Buffered Versus Nonbuffered Local Anesthetics and Local Pain Scores in Upper Eyelid Blepharoplasty: Randomized Controlled Trial.

PURPOSE: This split-face study aimed to see whether different types of local anesthetics or their buffered/nonbuffered combinations produce lower pain scores in upper eyelid blepharoplasty. METHODS: The study involved 288 patients, randomly divided into 9 groups: 1) 2% lidocaine with epinephrine-Lid + Epi; 2) 2% lidocaine with epinephrine and 0.5% bupivacaine (1:1)-Lid + Epi + Bupi; 3) 2% lidocaine with 0.5% bupivacaine (1:1)-Lid + Bupi; 4) 0.5% bupivacaine-Bupi; 5) 2% lidocaine-Lid; 6) 4% articaine hydrochloride with epinephrine-Art + Epi; 7) buffered 2% lidocaine/epinephrine with sodium bicarbonate (SB) in a 3:1 ratio-Lid + Epi + SB; 8) buffered 2% lidocaine with SB in a 3:1 ratio-Lid + SB; 9) buffered 4% articaine hydrochloride/epinephrine with SB in a 3:1 ratio-Art + Epi + SB. Following the injection of the first eyelid and a 5-minute period of soft pressure on the injection site, patients were asked to rate their pain level on the Wong-Baker Face Pain Rating Visual Analogue Scale. Rating of the pain level was repeated 15 and 30 minutes following anesthetic administration. RESULTS: The lowest pain scores at the first time point were observed in Lid + SB when compared with all of the other groups ( p < 0.05). At the final time point, significantly lower scores were also observed in Lid + SB, Lid + Epi + SB, and Art + Epi + SB when compared with the Lid + Epi group ( p < 0.05). CONCLUSION: These findings could help surgeons select an appropriate combination of local anesthetics, particularly in patients with lower pain threshold and tolerance because buffered combinations of local anesthetics produce significantly lower pain scores compared with nonbuffered solutions.

Galectin-1 in Pancreatic Ductal Adenocarcinoma: Bridging Tumor Biology, Immune Evasion, and Therapeutic Opportunities.

Pancreatic Ductal Adenocarcinoma (PDAC) remains one of the most challenging malignancies to treat, with a complex interplay of molecular pathways contributing to its aggressive nature. Galectin-1 (Gal-1), a member of the galectin family, has emerged as a pivotal player in the PDAC microenvironment, influencing various aspects from tumor growth and angiogenesis to immune modulation. This review provides a comprehensive overview of the multifaceted role of Galectin-1 in PDAC. We delve into its contributions to tumor stroma remodeling, angiogenesis, metabolic reprogramming, and potential implications for therapeutic interventions. The challenges associated with targeting Gal-1 are discussed, given its pleiotropic functions and complexities in different cellular conditions. Additionally, the promising prospects of Gal-1 inhibition, including the utilization of nanotechnology and theranostics, are highlighted. By integrating recent findings and shedding light on the intricacies of Gal-1's involvement in PDAC, this review aims to provide insights that could guide future research and therapeutic strategies.

Parathyroid carcinoma in chronic renal disease - a case series of three patients and review of literature.

BACKGROUND: Apart from being a rare endocrine tumor, parathyroid carcinoma is also one of the rarest malignancies in human beings. Parathyroid carcinoma is even more uncommon in haemodialysis patients with end-stage renal disease. The pathogenesis of parathyroid hyperplasia in haemodialysis patients is well known, but the mechanism of development of parathyroid carcinoma in these patients remains unclear. METHODS: Three cases of parathyroid carcinoma in haemodialysis patients are presented in this study: a 69-year-old male patient and two female patients (67 and 61 years old). In all cases parathyroid carcinoma infiltrated the ipsilateral thyroid lobe and in one patient the right laryngeal nerve was involved as well. One patient underwent three surgical procedures. RESULTS: After surgical treatment, all patients were normocalcaemic and showed a significant reduction in PTH levels. CONCLUSION: In patients with secondary hyperparathyroidism, who develop parathyroid carcinoma, surgical resection is the only viable treatment option.

Necrotizing Skin and Soft Tissue Infection after Gluteal Augmentation in a Perioperatively Asymptomatic COVID-19 Patient-Complications of the Post-Lockdown Era? A Case Report.

Introduction: Aesthetic surgery procedures are generally done in a relatively healthy population and carry a rather low risk compared to other surgical specialties. The incidence of complications in aesthetic surgery varies greatly depending on the type, wound cleanliness regarding the anatomical site, complexity of the surgery, patient's age, and comorbidities but is generally considered low. The overall incidence of surgical site infections (SSIs) in all aesthetic surgical procedures is around 1% in most of the literature while cases of necrotizing soft tissue infections are mostly found as individual reports. In contrast, treating COVID-19 patients is still challenging with many diverse outcomes. Surgical stress and general anesthesia are known mediators of cellular immunity impairment while studies regarding COVID-19 infection unquestionably have shown the deterioration of adaptive immunity by SARS-CoV-2. Adding COVID-19 to the modern surgical equation raises the question of immunocompetence in surgical patients. The main question of the modern post-lockdown world is: what could be expected in the postoperative period of perioperatively asymptomatic COVID-19 patients after aesthetic surgery? Case report: Here, we present a purulent, complicated, necrotizing skin and soft tissue infection (NSTI) after gluteal augmentation most likely triggered by SARS-CoV-2-induced immunosuppression followed by progressive COVID-19 pneumonia in an otherwise healthy, young patient. To the best of our knowledge, this is the first report of such adverse events in aesthetic surgery related to COVID-19. Conclusion: Aesthetic surgery in patients during the incubation period of COVID-19 or in asymptomatic patients could pose a significant risk for surgical complications, including severe systemic infections and implant loss as well as severe pulmonary and other COVID-19-associated complications.

Necrotizing Fasciitis-Severe Complication of Bullous Pemphigoid: A Systematic Review, Risk Factors, and Treatment Challenges.

Background and objectives: Bullous pemphigoid (BP), the most common subepidermal autoimmune skin blistering disease (AIBD) has an estimated annual incidence of 2.4 to 42.8 new cases per million in different populations, designating it an orphan disease. Characterized by disruption of the skin barrier combined with therapy-induced immunosuppression, BP could pose a risk for skin and soft tissue infections (SSTI). Necrotizing fasciitis (NF) is a rare necrotizing skin and soft tissue infection, with a prevalence of 0.40 cases per 100,000 to 15.5 cases per 100,000 population, often associated with immunosuppression. Low incidences of NF and BP classify them both as rare diseases, possibly contributing to the false inability of making a significant correlation between the two. Here, we present a systematic review of the existing literature related to the ways these two diseases correlate. Materials and methods: This systematic review was conducted according to the PRISMA guidelines. The literature review was conducted using PubMed (MEDLINE), Google Scholar, and SCOPUS databases. The primary outcome was prevalence of NF in BP patients, while the secondary outcome was prevalence and mortality of SSTI in BP patients. Due to the scarcity of data, case reports were also included. Results: A total of 13 studies were included, six case reports of BP complicated by NF with six retrospective studies and one randomized multicenter trial of SSTIs in BP patients. Conclusions: Loss of skin integrity, immunosuppressive therapy, and comorbidities commonly related to BP patients are risk factors for necrotizing fasciitis. Evidence of their significant correlation is emerging, and further studies are deemed necessary for the development of BP-specific diagnostic and treatment protocols.

Primary Melanoma Histopathologic Predictors of Sentinel Lymph Node Positivity: A Proposed Scoring System for Risk Assessment and Patient Selection in a Clinical Setting.

Background and Objectives: The careful selection of adequate SLNB candidates not only aims at reducing the surgical risk while identifying SLN metastasis, but also plays a crucial role in identifying the patients eligible for adjuvant therapy. Objectives: The purpose of our study was to investigate the clinical and histologic aspects of primary melanomas that correlate with the likelihood of a positive SLNB result. Materials and Methods: A total of 101 primary melanoma patients who underwent sentinel lymph node biopsies were included in the study. General patient demographics were obtained as well as localization and melanoma-specific characteristics of primary melanoma from histologic reports in addition to data derived from SLNB melanoma histopathology reports. Results: The patients with positive SLN results had a statistically significant increased Breslow thickness (3.8 mm vs. 1.97 mm, p = 0.002), higher mitotic index rate (5/mm2 vs. 2/mm2, p = 0.009), as well as the presence of ulceration (68.4% vs. 31.6%, p = 0.007). Univariate regression analysis showed the Breslow thickness (p = 0.008), the mitotic index rate (p = 0.054), the presence of ulceration (p = 0.009), as well as the pT3-4 stage (p = 0.009) to be significant predictors of SLN positivity. The optimal cut-off values for Breslow thickness and the number of mitoses scores were determined based on ROC curve analysis. Using the Breslow thickness, mitotic index rate, presence of ulceration, and pT3-4 stage significant coefficients from the univariate regression model, a chance prediction score was developed. Conclusions: The newly developed and proposed scoring system can aid in patient selection for SLN biopsy by facilitating a more efficient risk assessment in the detection of lymph node metastases in melanoma patients.

Reconstruction of Moderately and Severely Atrophic Scalp-A Multicentric Experience in Surgical Treatment of Patients Irradiated for Tinea Capitis in Childhood and Surgical Algorithm.

Background and Objectives: Before the introduction of griseofluvin, the use of X-ray radiation was the treatment of choice for tinea capitis. More than half a century later various types of tumors have been found to be associated with childhood irradiation due to tinea capitis, most commonly cancers of the head and neck, as well as brain tumors. The often unusually aggressive and recurrent nature of these tumors necessitates the need for repeated surgeries, while the atrophic skin with an impaired vascular supply due to radiation often poses an additional challenge for defect reconstruction. We present our experience in the surgical treatment of such patients. Materials and Methods: This is a retrospective cohort study. In this study, 37 patients treated for acquired defects of the scalp with a history of irradiation therapy due to tinea capitis in childhood were included in this study, 24 male and 13 female patients. The mean age at the first appointment was 60.6 ± 7.8, with the youngest included patient being 46 and the oldest being 75 years old. Patients' characteristics, surgical treatment, and complications were analyzed and a reconstructive algorithm was developed. Results: Local flaps were used for reconstruction in 34 patients, direct sutures were used in 10 patients and 20 patients received split-thickness skin grafts for coverage of both primary and secondary defects for reconstruction of flap donor sites. One regional flap and one dermal substitute covered by an autologous skin graft were also used for reconstruction. Complications occurred in 43.2% of patients and were significantly associated with the presence of comorbidities (p = 0.001), aseptic bone necrosis (p = 0.001), as well as skin atrophy in frontal, occipital, and parietal region (p = 0.001, p = 0.042 and p = 0.001, respectively). A significant correlation between major complications and moderate skin atrophy was found only in the parietal region (p = 0.026). Conclusions: Unfortunately, many protocols developed for scalp reconstruction are not applicable in the setting of severe or diffuse scalp skin atrophy associated with high tumor recurrence rate and radiation-induced vascular impairment, such as in tinea capitis patients in Serbia. An algorithm has been developed based on the authors' experience in managing these patients.

Preoperative Anxiety is Associated With Postoperative Complications in Vascular Surgery: A Cross-Sectional Study.

BACKGROUND: Preoperative anxiety is associated with increased morbidity and/or mortality in surgical patients. This study investigated the incidence, predictors, and association of preoperative anxiety with postoperative complications in vascular surgery. METHODS: Consecutive patients undergoing aortic, carotid, and peripheral artery surgery, under general and regional anesthesia, from February until October 2019 were included in a cross-sectional study. Anesthesiologists assessed preoperative anxiety using a validated Serbian version of the Amsterdam Preoperative Anxiety and Information Scale. Patients were divided into groups with low/high anxiety, both anesthesia- and surgery-related. Statistical analysis included multivariate linear logistic regression and point-biserial correlation. RESULTS: Of 402 patients interviewed, 16 were excluded and one patient refused to participate (response rate 99.7%). Out of 385 patients included (age range 39-86 years), 62.3% had previous surgery. High-level anesthesia- and surgery-related anxieties were present in 31.2 and 43.4% of patients, respectively. Independent predictors of high-level anesthesia-related anxiety were having no children (OR = 0.443, 95% CI: 0.239-0.821, p = 0.01), personal bad experiences with anesthesia (OR = 2.294, 95% CI: 1.043-5.045, p = 0.039), and time since diagnosis for ≥ 4 months (OR = 1.634, 95% CI: 1.023-5.983, p = 0.04). The female sex independently predicted high-level surgery-related preoperative anxiety (OR = 2.387, 95% CI: 1.432-3.979, p = 0.001). High-level anesthesia-related anxiety correlated with postoperative mental disorders (rpb = 0.193, p = 0.001) and pulmonary complications (rpb = 0.104, p = 0.042). Postoperative nausea (rpb = 0.111, p = 0.03) and postoperative mental disorders (rpb = 0.160, p = 0.002) correlated with high-level surgery-related preoperative anxiety. CONCLUSIONS: Since preoperative anxiety affects the postoperative course and almost every third patient experiences anxiety preoperatively, routine screening might be recommended in vascular surgery.

Patients' Fears and Perceptions Associated with Anesthesia.

Background and Objectives: It has been suggested that intense feelings of fear/anxiety and significant patient concerns may affect the perioperative course. Those findings emphasize the importance of surgical patients' preoperative feelings. Still, current knowledge in this area is based on a limited number of studies. Thus, we think that there is a need to further explore patients' preoperative fears, better characterize risk factors and reasons for their occurrence, and evaluate patients' perspectives associated with anesthesia. Materials and Methods: A total of 385 patients undergoing vascular surgery were preoperatively interviewed using a questionnaire that included demographics and questions related to patients' fears and perceptions of anesthesia. Statistical analyses included descriptive statistics, Pearson's χ2 and McNemar tests, and multivariate ordinal logistic regression. Results: The main causes of patients' preoperative fear were surgery (53.2%), potential complications (46.5%), and anesthesia (40%). Female sex was a predictor of surgery and anesthesia-related fear (OR = 3.07, p = 0.001; OR = 2.4, p = 0.001, respectively). Previous experience lowered the fear of current surgery (OR = 0.65, p = 0.031) and anesthesia (OR = 0.6, p = 0.017). Type of surgery, type of anesthesia, educational and socioeconomic status, and personal knowledge of an anesthesiologist affected specific anesthesia-related fears. Over 25% of patients did not know that an anesthesiologist is a physician, and only 17.7% knew where anesthesiologists work. Level of education and place of residence influenced patients' perceptions of anesthesia. Conclusions: Anesthesia-related fears are affected by the type of surgery/anesthesia, experience with previous surgery, and personal knowledge of an anesthesiologist. Women, patients with lower education levels, and patients with poorer socioeconomic status are at higher risk of developing those fears. The perception of anesthesiologists is inadequate, and knowledge of anesthesia is poor. Promotion of patient education regarding anesthesia is needed to alleviate those fears and increase understanding of anesthesia.

Predictive Value of Calcium Test for Preoperative Diagnosis of Medullary Thyroid Carcinoma in Patients With Moderately Elevated Basal Calcitonin.

OBJECTIVE: Medullary thyroid carcinoma (MTC) can be very aggressive, and early diagnosis is based on routine measurement of serum calcitonin (CT) and RET genetic testing for hereditary forms. Basal serum CT (bCT) concentrations are useful in the early detection of MTC, although it is still unclear whether they can also be used for the differential diagnosis between MTC and C-cell hyperplasia (CCH). Since false-positive results can be obtained with the basal measurement of CT, a provocative test to evaluate stimulated CT (sCT) is often needed. The objective of this study was to investigate the utility of a calcium gluconate test for CT in distinguishing MTC from CCH, a precancerous condition in hereditary forms of MTCs but with unclear significance in sporadic MTCs. METHODS: A total of 74 patients underwent the calcium loading test before thyroidectomy, and bCT and sCT levels were compared with histologic results by receiver operating characteristic plot analyses. RESULTS: A peak CT level of 388.4 pg/mL after stimulation with calcium gluconate was able to significantly distinguish patients with MTC from those with CCH and those without C-cell pathology, with 81.8% sensitivity and 36.5% specificity. A bCT level of 16.1 pg/mL was able to distinguish between these 2 groups of patients with a sensitivity of 90%. CONCLUSION: High-dose calcium test is an effective procedure that can be applied for differential diagnosis of MTC and CCH. Reference ranges for calcium sCT levels and CT thresholds in different groups of patients have been identified.

Increased Severity of Ulcerative Colitis in the Terminal Phase of the Metabolic Syndrome.

Ulcerative colitis is chronic immune-mediated disorder that affects primarily colonic mucosa. The metabolic syndrome has increasing global prevalence with a significant impact on biology of chronic diseases, such as ulcerative colitis. Today it is known that the metabolic syndrome attenuates severity of ulcerative colitis. Still, there is no evidence that different stages of metabolic syndrome alter the course of the ulcerative colitis. The aim of this study was to dissect out how progression of the metabolic syndrome impacted the biology of ulcerative colitis and severity of clinical presentation. Seventy-two patients (41 men and 31 women, 22-81 years old) were enrolled in this observational cross-sectional study. Concentrations of pro- and anti-inflammatory cytokines in serum and feces samples were measured and phenotype of colon infiltrating cells was analyzed. Patients in the terminal phase of the metabolic syndrome have clinically and pathohistologically more severe form of ulcerative colitis, which is followed by decreased concentrations of systemic galectin-1, increased values of systemic pro-inflammatory mediators and increased influx of lymphocytes in affected colon tissue. Our data suggest that reduced concentrations of galectin-1 and predomination of the pro-inflammatory mediators in patients with terminal stage of the metabolic syndrome enhance local chronic inflammatory response and subsequent tissue damage, and together point on important role of galectin-1 in immune response in ulcerative colitis patients with the metabolic syndrome.

Effectiveness of different doses and routes of administration of tranexamic acid for total hip replacement.

PURPOSE: The aim of the study is to show the therapeutic efficacy, safety, and cost-benefit of using tranexamic acid (TXA), as well as the superiority of the route of administration and amount of dose in primary cementless total hip replacement (THR). METHODS: In this prospective, randomized, double-blind study, we divided 200 patients into five groups of 40 patients each. The placebo group did not receive TXA. Three groups received 2 g TXA each (intravenous, topical, and combined intravenous + topical), while the fifth, combined + group, received 4 g TXA. Total blood loss was calculated, number of transfusions and thromboembolic vascular incidents were monitored, and a cost-benefit analysis of the use of TXA was performed. RESULTS: Regardless of the route of administration, TXA statistically significantly reduced total blood loss (p = 0.000) and the need for transfusion (p = 0.000) compared with placebo. Total blood loss and the need for allogenic blood transfusion were statistically significantly reduced in the combined + group compared with placebo, and also compared with all other groups. Post-operative thromboembolic vascular incidents were not reported. The cost-benefit of using TXA in THR is associated with reduction of transfusion costs. CONCLUSIONS: None of the TXA administration routes are superior to others, but multiple doses could statistically significantly reduce blood loss and transfusion requirements, which should be the subject of future researches.

A Mobile Crowd Sensing Application for Hypertensive Patients.

Mobile crowd sensing (MCS) is an application that collects data from a network of conscientious volunteers and implements it for the common or personal benefit. This contribution proposes an implementation that collects the data from hypertensive patients, thus creating an experimental database using the cloud service Platform as a Service (PaaS). The challenge is to perform the analysis without the main diagnostic feature for hypertension-the blood pressure. The other problems consider the data reliability in an environment full of artifacts and with limited bandwidth and battery resources. In order to motivate the MCS volunteers, a feedback about the patient's current status is created, provided by the means of machine-learning (ML) techniques. Two techniques are investigated and the Random Forest algorithm yielded the best results. The proposed platform, with slight modifications, can be adapted to the patients with other cardiovascular problems.

Risk factors associated with intrathyroid extension of thyroid microcarcinomas.

PURPOSE: The aims of this study were to investigate the rate of intrathyroid extension of papillary thyroid microcarcinoma (PTMC) in patients operated for benign thyroid disease and to identify independent risk factors associated with it. METHODS: A retrospective study of 301 patients operated for benign thyroid diseases (hyperthyroid diseases, multinodular goitre, Hashimoto thyroiditis and benign thyroid tumours) was performed at a high-volume endocrine surgery unit of a tertiary referral academic hospital, in a 5-year period. These patients had a PTMC incidentally discovered on definite histopathological findings following total or near-total thyroidectomy. Since distinguishing between intrathyroid extension of PTMC as the result of intrathyroid dissemination or as the result of multicentricity is challenging, we observed them together as multifocality. In statistical analysis, we used standard descriptive statistics and univariate and multivariate logistic regression analysis to determine independent risk factors associated with multifocality. RESULTS: In our study, there were 85.4% females and 14.6% males with a median age of 54 years. A multinodular goitre (32.5%) was the most common indication for an operation. Most patients (68.4%) had a PTMC that was 5 mm or smaller. The most frequent histological variants of PTMC were the follicular variant (52.8%), followed by the papillary variant (22.6%) and the mixed follicular-papillary variant (18.6%). A multifocal PTMC was present in 26.6% of cases. An independent protective factor for multifocality of PTMC was a thyroid gland that weighed more than 38 g (OR 0.55, 95% CI 0.31-0.97, p = 0.039). Size of PTMC greater than 5 mm was an independent risk factor for a multifocal PTMC (OR 3.26, 95% CI 1.85-5.75, p = 0.000). Finally, the mixed follicular-papillary variant of PTMC represents an independent risk factor for a multifocal PTMC (OR 2.42, 95% CI 1.09-5.36, p = 0.030). CONCLUSIONS: Intrathyroid extension is present in more than a quarter of PTMCs found in patients operated for benign thyroid disease. Independent risk factors for intrathyroid extension are size of PTMC greater than 5 mm and the mixed follicular-papillary variant of PTMC, while a large thyroid gland is an independent protective factor.

Fecal Galectin-3: A New Promising Biomarker for Severity and Progression of Colorectal Carcinoma.

BACKGROUND AND OBJECTIVES: The aim of the study was to determine systemic and fecal values of galectin-3 and pro- and anti-inflammatory cytokines in patients with CRC and the relationship with clinicopathological aspects. METHODS: Concentrations of galectin-3, TNF-α, TGF-ß, IL-10, and IL-1ß were analyzed in samples of blood and stool of 60 patients with CRC. RESULTS: Systemic concentration of TNF-α was significantly lower in patients with severe diseases (advanced TNM stage, nuclear grade, and poor histological differentiation) as in patients with more progressive CRC (lymph and blood vessel invasion, presence of metastasis). Fecal values of anti-inflammatory cytokines TGF-ß and IL-10 were increased in patients with severe stadium of CRC. Fecal concentration of Gal-3 was enhanced in CRC patients with higher nuclear grade, poor tumor tissue differentiation, advanced TNM stage, and metastatic disease. Gal-3/TNF-α ratio in sera and feces had a higher trend in patients with severe and advanced diseases. Positive correlation between fecal Gal-3 and disease severity, tumor progression, and biomarkers AFP and CEA, respectively, was also observed. CONCLUSIONS: Predomination of Gal-3 in patients with advanced diseases may implicate on its role in limiting ongoing proinflammatory processes. The fecal values of Gal-3 can be used as a valuable marker for CRC severity and progression.