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Introduction: Data on melanoma incidence and mortality in Montenegro is only partially complete. GLOBOCAN and EUCAN reports estimate melanoma incidence in Montenegro to be between 4.6-7.3 cases/100 000. At least 50% of all metastatic melanoma cell lines carry an activating mutation in the BRAF oncogene. The treatment of advanced melanoma with the selective BRAF inhibitors, such as vemurafenib demonstrated improvement in progression free interval and overall survival when compared to conventional chemotherapy treatment. Up to 95% of patients treated with vemurafenib experience skin toxicity. Material and methods: Five patients with metastatic melanoma have been treated with vemurafenib at the Clinic for Oncology and Radiotherapy Podgorica, Montenegro, during the period 2013-2014. They were treated with standard dose (960 mg twice a day, per os). Data about the occurrence and management of skin side-effects in these patients were retrospectively collected from medical charts. Severity of side-effects was graded using the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. Results: In 2013, 41 new cases of melanoma were registered in Montenegro, 20 (48.7%) male and 21 (51.3%) female. In 2014, 49 new cases of melanoma were registered, 27 (55.1%) male and 22 (44.9%) female. Two out of five (40%) vemurafenib treated patients experienced photosensitivity, three (60%) had rash eruptions, four (80%) developed alopecia, and two (40%) had dry skin problems. Alteration in nevus color and size occurred in one (20%) patient, and two (40%) patients developed new pigmented lesions. Conclusion: Skin side effects associated with vemurafenib are plentiful, but generally manageable with supportive care measures. In our experience, majority of described side-effects were of grade 1 or 2, and none required dose modifications, or discontinuation of the therapy. Our experience suggests that patients taking BRAF inhibitors should have regular full body skin assessments, both prior to the beginning of the therapy and periodically after its onset. Clinicians should be aware of the skin related toxicities, in order to minimize their impact on treatment efficacy and patients' quality of life.

Abstract Background Environmental monitoring for pharmaceuticals and endocrine disruptors in the aquatic environment traditionally employs a variety of methods including analytical chemistry, as well as a variety of histological and biochemical endpoints that correlate with the fish fitness. It is now clear that analytical chemistry alone is insufficient to identify aquatic environments that are compromised because these measurements do not identify the biologically available dose. The biological endpoints that are measured are important because they relate to known impairments; however, they are not specific to the contaminants and often focus on only a few known endpoints. These studies can be enhanced by looking more broadly at changes in gene expression, especially if the analysis focuses on biochemical pathways. The present study was designed to obtain additional information for well-characterized sites adjacent to sewage treatment plants in MN that are thought to be impacted by endocrine disruptors. Results Here we examine five sites that have been previously characterized and examine changes in gene expression in fathead minnows (Pimephales promelas) that have been caged for 48 h in each of the aquatic environments. We find that the gene expression changes are characteristic and unique at each of the five sites. Also, fish exposed to two of the sites, 7 and 12, present a more aggressive behavior compared to control fish. Conclusion Our results show that a short-term exposure to sewage treatment plant effluents was able to induce a site-specific gene expression pattern in the fathead minnow gonad and liver. The short-term exposure was also enough to affect fish sexual behavior. Our results also show that microarray analysis can be very useful at determining potential exposure to chemicals, and could be used routinely as a tool for environmental monitoring.

Background: Radial forearm free flap (RFFF) is considered one of the workhorses in modern head and neck reconstruction surgery due to its technical simplicity, versatility and less time-consuming harvest. Methods: In this report, we present the case of a 56-year-old woman with sublingual squamous cell carcinoma (SCC) who underwent surgical resection and reconstruction of the defect with a RFFF. Results: The preoperative Allen test showed normal blood flow, and the ultrasound did not recognize any blood vessel abnormalities in the left arm. However, during the RFFF harvest, when the dissection of the pedicle came to the cubital fossa, there was no brachial artery bifurcation. While trying to find the bifurcation, the dissection almost came to the axillary region. Hence, the RFFF was converted to a pedicle flap and was pulled through to the intraoral defect where it was used for reconstruction. Conclusions: Hence, during the preoperative radiological ultrasound, besides the usual characteristics such as the radial artery diameter, flow and possible obstructions, it is also important to explore if there are any other anatomical abnormalities that could influence the operation.

Background: Oral squamous cell carcinoma (OSCC) causes considerable morbidity and mortality rates, posing a major global health burden. The management of the OSCC is multidisciplinary, but still the gold standard is surgical resection and reconstruction of the postablative defect. The appearance of secondary primary OSCC is not uncommon; however, it is quite rare that it appears on the skin of the flap that was used for reconstruction during the previous surgical therapy. Methods: We present three cases in which a secondary primary OSCC appeared on the skin of two radial forearm free flaps and two on regional pectoralis major flaps. Results: Our case series show that, although relatively rare, there is a chance of a secondary primary tumor on the flap used for intraoral reconstruction after the first oncological reconstruction. According to the latest and available literature, there is still no explanation of the underlying mechanism that leads to this occurrence. Conclusions: The learning point of this case series should be that, aside from the neck metastasis or recurrence of the primary oral cancer, the clinicians should also bear in mind that the flap itself should be physically examined in detail.

Background: This report contributes to VASCUNET data on treating peripheral artery disease (PAD) in Serbia, addressing sex differences, revascularization types, procedure characteristics, and morbidity and mortality., Methods: SerbVasc, part of the VASCUNET collaboration, includes vascular procedures from 27 Serbian hospitals. Data from 1681 PAD patients were analyzed, focusing on sex disparities, diabetes prevalence, previous procedures, infection and tissue loss, and morbidity and mortality rates., Results: Males formed the majority, comprising 1169 (69.5%) of the patients. Men were significantly more often treated open surgically compared to women (77.6% vs 68.0%; p=0.000). Diabetes stood at 40.2% prevalence. Smoking history was noted in 61.9% of patients, predominantly males. Complication rates stood at 7.5%, with diabetic patients more prone to reinterventions and graft restenosis. The in-hospital mortality rate was 1.6%, with significant predictors of mortality including urgent procedures and recent myocardial infarction. The severity of the infection was correlated with diabetes (r=0.250, p=0.000) and previous amputations (r=0.186, p=0.000). Patients undergoing revascularization followed by minor amputations had a significantly lower incidence of major amputation (0.1% vs 2.9%, p=0.000)., Conclusions: SerbVasc data provides a comprehensive overview of PAD management, highlighting the significant impact of diabetes and smoking on disease progression and outcomes., Clinical Impact: This study highlights critical aspects of PAD management in developing countries, emphasizing sex differences, risk factors, and outcomes. Males predominated and are more likely to undergo open surgery. Diabetes and smoking significantly influenc disease progression, with diabetic patients experiencing higher rates of graft restenosis and reinterventions. Urgent procedures and recent myocardial infarctions are key predictors of in-hospital mortality. Combining revascularization with minor amputations reduced major amputation rates. These findings provide valuable data for tailoring treatment strategies, optimizing resource allocation, and improving outcomes for PAD patients, with implications extending beyond Serbia to similar healthcare systems., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Recently, microRNAs (miR) were identified to have potential links with oral squamous cell carcinoma (OSCC) and oropharyngeal squamous cell carcinoma (OPSCC) oncogenesis, specifically miR-21. Since HPV is a major risk factor for the development of these diseases, we aimed to search the literature regarding miR-21 expression in both HPV-positive and HPV-negative OSCC/OPSCC. The search was performed in the PubMed (MEDLINE), Scopus, Web of Science, and Cochrane electronic databases. The research question was as follows: Is there a difference in the tissue expression of miR-21 between patients with HPV-positive and those with HPV-negative OSCC/OPSCC? After conducting a meticulous search strategy, four studies were included, and they had a pooled sample size of 621 subjects with OSCC and/or OPSCC. Three studies did not find any significant difference in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. The findings of this systematic review showed that there are no differences in miR-21 expression between HPV-positive and HPV-negative OSCC/OPSCC. Nevertheless, it is worth noting that there are still insufficient studies regarding this important subject, because understanding how HPV influences miR-21 expression and its downstream effects can provide insights into the molecular mechanisms underlying OSCC/OPSCC development and progression.

Antimicrobial resistance is recognised as one of the top threats healthcare is bound to face in the future. There have been various attempts to preserve the efficacy of existing antimicrobials, develop new and efficient antimicrobials, manage infections with multi-drug resistant strains, and improve patient outcomes, resulting in a growing mass of routinely available data, including electronic health records and microbiological information that can be employed to develop individualised antimicrobial stewardship. Machine learning methods have been developed to predict antimicrobial resistance from whole-genome sequencing data, forecast medication susceptibility, recognise epidemic patterns for surveillance purposes, or propose new antibacterial treatments and accelerate scientific discovery. Unfortunately, there is an evident gap between the number of machine learning applications in science and the effective implementation of these systems. This narrative review highlights some of the outstanding opportunities that machine learning offers when applied in research related to antimicrobial resistance. In the future, machine learning tools may prove to be superbugs' kryptonite. This review aims to provide an overview of available publications to aid researchers that are looking to expand their work with new approaches and to acquaint them with the current application of machine learning techniques in this field.

Purpose: Primary aim of the study was to investigate the status of different health-related quality of life (HRQoL) domains in postmenopausal women with osteoporosis and osteopenia, and to explore possible associations with bone microarchitecture and nutritional status., Methods: This was a single-center cross-sectional study that included 232 postmenopausal women, from which they were divided into three groups-osteoporosis (OP, N = 63), osteopenia (OPIA, N = 123), and control group (N = 46). Detailed medical history data and anthropometric measurements were taken from all women. Bone structure parameters were taken with DXA device, with additional analysis of bone microarchitecture status with Trabecular Bone Score (TBS). Nutritional status was assessed with Mini Nutritional Assessment (MNA) questionnaire, and HRQoL with Medical Outcomes Study Short Form-36 (SF-36) questionnaire., Results: Nutrition evaluation analysis have shown that patients in OP group had significantly lower values of MNA score compared to the OPIA group and control group (P = 0.005). Furthermore, a significant positive correlation was found between all of the SF-36 domains and MNA scores, while significant positive correlation was found between TBS values and Physical functioning (P < 0.001), Bodily pain (P = 0.027), Social functioning (P = 0.029), and Vitality domains (P = 0.041) in total investigated population. Further analyses were performed only in OP and OPIA groups, and TBS score showed significant positive correlation with Physical functioning (r = 0.248, P < 0.001) and Bodily pain domains as well (r = 0.180, P = 0.014), while MNA score positively correlated with each of the SF-36 domains. Multiple regression models have shown that MNA score retained significant association with each SF-36 domains, and TBS value with Physical functioning (P = 0.003), Social functioning (P = 0.012), and Vitality domains (P = 0.014)., Conclusion: This study highlights the associations that TBS has with some domains of HRQoL in postmenopausal women with osteoporosis and osteopenia. Moreover, nutritional status could play a role in the complex interplay between TBS and HRQoL., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The vastus lateralis muscle is one of the four muscles that make up the quadriceps femoris muscle, and it is also the largest of them. Some studies have shown that patients experience lower quality of life and muscle weakness after surgical treatment of thigh muscles in order to perform reconstructive surgery of the head and neck. The aim of our study was to assess the quantitative and qualitative function of the lower extremities using an isokinetic dynamometer and a validated questionnaire on subjective difficulties in patients who underwent reconstructive surgery with the vastus lateralis free flap. Fourteen participants aged 20-70 years who suffered from malignant tumor in the head and neck region. The free vastus lateralis flap was used for reconstruction. All patients underwent isokinetic dynamometric measurement with the isokinetic dynamometer to test the isokinetic functions of the thigh muscles after surgery. In addition, subjective assessment of the lower extremities was performed using the validated questionnaire Lower Extremity Functional Scale. All isometric dynamometer measurements of the donor leg were compared with those of the unoperated leg. Peak torque and average power were significantly lower in the operated leg compared with the unoperated leg after 60°/s extension (p = 0.018 for peak torque, p = 0.021 for average power) and 180°/s extension (p = 0.019 for peak torque, p = 0.015 for average power). On the other hand, there was no statistically significant difference in dynamometer measurements after 60°/s flexion (p = 0.700 for peak torque, p = 0.854 for average power, and 180°/s flexion (p = 0.634 for peak torque, p = 0.571 for average power). The median value for the LEFS was 65.5 (40.00-71.25). The results of this study showed that there is a significant deterioration regarding the biophysical properties of the operated leg after harvesting vastus lateralis free flap., Competing Interests: Declarations of competing interest None., (Copyright © 2023 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background and Objectives : Anticoagulants are a well-known risk factor for gastrointestinal bleeding (GIB). In recent years, direct oral anticoagulants (DOACs) have taken a leading role in the treatment and prevention of thromboembolic incidents. The aim of this study was to investigate the prevalence of DOAC-treated patients with GIB whose plasma drug concentrations exceeded the cut-off values reported in the literature and to evaluate their clinical characteristics. Materials and Methods : Patients who were admitted to the Intensive Care Unit in the period 2/2020-3/2022 due to GIB were prospectively included in the study and classified into three groups according to the prescribed type of DOAC (apixaban, rivaroxaban, and dabigatran). For all participants, it was determined if the measured plasma drug levels exceeded the maximum serum concentration (C max) or trough serum concentration (C trough ) obtained from the available data. A comparison of clinical parameters between the patients with and without excess drug values was performed. Results: There were 90 patients (54.4% men) included in the study, of whom 27 were treated with dabigatran, 24 with apixaban, and 39 with rivaroxaban. According to C max , there were 34 (37.8%), and according to C trough , there were 28 (31.1%) patients with excess plasma drug values. A statistically significant difference regarding excess plasma drug values was demonstrated between DOACs according to both C max ( p = 0.048) and C trough ( p < 0.001), with the highest rate in the group treated with dabigatran (55.6% for C max and 59.3% for C trough ). Multivariate logistic regression showed that age (OR 1.177, p = 0.049) is a significant positive and glomerular filtration rate (OR 0.909, p = 0.016) is a negative predictive factor for excess plasma drug values. A total of six (6.7%) patients had fatal outcomes. Conclusions : Plasma drug concentrations exceed cut-off values reported in the literature in more than one-third of patients with GIB taking DOAC, with the highest rate in the dabigatran group. Clinicians should be more judicious when prescribing dabigatran to the elderly and patients with renal failure. In these patients, dose adjustment, plasma drug monitoring, or substitution with other, more appropriate DOACs should be considered.

This study aimed to examine the frequency of temporomandibular disorder among biomedical students and relate its occurrence to lifestyle habits. A cross-sectional collection of data was carried out and included a total of 676 examinees through a questionnaire that had 73 questions: general information and lifestyle habits, the Fonseca Anamnestic index (FAI), the Jaw Function Limitation Scale (JFLS), and the Perceived Stress Questionnaire (PSQ). The statistical analyses between three or more groups were conducted using the one-way analysis of variance (ANOVA) with post hoc Scheffé test or Kruskal-Wallis test with post hoc Dunn's test for quantitative variables. The comparison of qualitative variables was conducted using the Chi-square test, while the correlations were determined using Spearman's correlation test. The analysis showed that a higher frequency of moderate or severe TMD was observed in subjects who were smokers ( p < 0.001) compared to non-smokers. Subjects who consumed more coffee had moderate to severe TMD compared to subjects who consumed a lesser amount ( p < 0.001). Furthermore, a positive correlation between the amount of stress and the severity of TMD was found. Our study implies that students of biomedical studies have an increased risk for TMD and that there is a link with their lifestyle habits.

Obstructive sleep apnea (OSA) has become major public concern and is continuously investigated in new aspects of pathophysiology and management. Urotensin II (UII) is a powerful vasoconstrictor with a role in cardiovascular diseases. The main goal of this study was to evaluate serum UII levels in OSA patients and matched controls. A total of 89 OSA patients and 89 controls were consecutively enrolled. A medical history review and physical examination of the participants was conducted, with polysomnography performed in the investigated group. UII levels and other biochemical parameters were assessed according to the standard laboratory protocols. The median AHI in the OSA group was 39.0 (31.4-55.2) events/h, and they had higher levels of hsCRP when compared to control group (2.87 ± 0.71 vs. 1.52 ± 0.68 mg/L; p < 0.001). Additionally, serum UII levels were significantly higher in the OSA group (3.41 ± 1.72 vs. 2.18 ± 1.36 ng/mL; p < 0.001), while positive correlation was found between UII levels and hsCRP (r = 0.450; p < 0.001) and systolic blood pressure (SPB) (r = 0.317; p < 0.001). Finally, multiple regression analysis showed significant association of UII levels with AHI (0.017 ± 0.006, p = 0.013), SBP (0.052 ± 0.008, p < 0.001) and hsCRP (0.538 ± 0.164, p = 0.001). As UII levels were associated with blood pressure and markers of inflammation and OSA severity, it might play an important role in the complex pathophysiology of OSA and its cardiometabolic complications.

Obesity is a disorder identified by an inappropriate increase in weight in relation to height and is considered by many international health institutions to be a major pandemic of the 21st century. The gut microbial ecosystem impacts obesity in multiple ways that yield downstream metabolic consequences, such as affecting systemic inflammation, immune response, and energy harvest, but also the gut-host interface. Metabolomics, a systematized study of low-molecular-weight molecules that take part in metabolic pathways, represents a serviceable method for elucidation of the crosstalk between hosts' metabolism and gut microbiota. In the present review, we confer about clinical and preclinical studies exploring the association of obesity and related metabolic disorders with various gut microbiome profiles, and the effects of several dietary interventions on gut microbiome composition and the metabolome. It is well established that various nutritional interventions may serve as an efficient therapeutic approach to support weight loss in obese individuals, yet no agreement exists in regard to the most effective dietary protocol, both in the short and long term. However, metabolite profiling and the gut microbiota composition might represent an opportunity to methodically establish predictors for obesity control that are relatively simple to measure in comparison to traditional approaches, and it may also present a tool to determine the optimal nutritional intervention to ameliorate obesity in an individual. Nevertheless, a lack of adequately powered randomized trials impedes the application of observations to clinical practice.

While surgical therapy for head and neck cancer (HNC) is showing improvement with the advancement of reconstruction techniques, the focus in these patients should also be shifting to supportive pre and aftercare. Due to the highly sensitive and anatomically complex region, these patients tend to exhibit malnutrition, which has a substantial impact on their recovery and quality of life. The complications and symptoms of both the disease and the therapy usually make these patients unable to orally intake food, hence, a strategy should be prepared for their nutritional management. Even though there are several possible nutritional modalities that can be administrated, these patients commonly have a functional gastrointestinal tract, and enteral nutrition is indicated over the parenteral option. However, after extensive research of the available literature, it seems that there is a limited number of studies that focus on this important issue. Furthermore, there are no recommendations or guidelines regarding the nutritional management of HNC patients, pre- or post-operatively. Henceforth, this narrative review summarizes the nutritional challenges and management modalities in this particular group of patients. Nonetheless, this issue should be addressed in future studies and an algorithm should be established for better nutritional care of these patients.

Competing Interests: The authors declare no conflict of interest.

It has been well established that diabetes mellitus (DM) is considered as a core risk factor for the development of cardiovascular diseases. However, what is less appreciated is the fact that DM may affect cardiac function irrespective of cardiac pathologies to which it contributes, such as coronary artery disease and hypertension. Although echocardiography provides accurate and reproducible diagnostic and prognostic data in patients with DM, its use in these patients is still underappreciated, resulting in progression of DM-related heart failure in many patients. Hence, in the present review, we aimed to discuss the role of echocardiography in the contemporary management of diabetic cardiomyopathy (DCM), as well as the role of emerging echocardiographic techniques, which may contribute to earlier diagnosis and more appropriate management of this complication of DM. In order to improve outcomes, focus must be placed on early diagnosis of this condition using a combination of echocardiography and emerging biomarkers, but perhaps the more important thing is to change perspective when it comes to the clinical importance of DCM.

Advanced glycation end products (AGEs) represent an endogenously produced or exogenously derived group of compounds derived from nonenzymatic glycation. Recent experimental studies are suggesting that AGEs could play an important role in the skin's quality and its aging process. Hence, the aim of this study was to clinically evaluate the AGEs and skin quality parameters across different age groups in the general population. The study included 237 participants. Melanin, erythema, hydration, friction and transepidermal water loss (TEWL) were evaluated using noninvasive probes, while AGEs were evaluated using a skin autofluorescence reader. There was a significant positive correlation between AGEs and the amount of melanin ( p < 0.001), erythema ( p < 0.001) and TEWL ( p < 0.001), while there was a significant negative correlation between AGEs and hydration ( p < 0.001) and friction ( p < 0.001). After dividing the sample into three groups depending on their age, in all three groups, there was a significant positive correlation between AGEs and the melanin count ( p < 0.001) and TEWL ( p < 0.001), while there was a significant negative correlation between AGEs and skin hydration ( p < 0.001). Multiple linear regression analysis showed that the level of AGEs as a dependent variable retained a significant association with age ( p < 0.001), melanin ( p < 0.001), erythema ( p = 0.005) and TEWL ( p < 0.001) as positive predictors. Moreover, AGEs retained a significant association with skin hydration ( p < 0.001) and friction ( p = 0.017) as negative predictors. These outcomes imply that AGEs could be linked with the complex physiology of the skin and its aging process.

We present the case of a 64-year-old man diagnosed with large B-cell lymphoma who relapsed twice after standard-of-care therapy. Due to persisting cytopenia, Next generation sequencing analysis was performed, revealing a small TP53 -mutated clone. As a third-line therapy, the patient was treated with CAR-T cells, which resulted in complete remission. However, this treatment also led to the expansion of the TP53 -mutated clone and therapy-related myelodysplasia with a complex aberrant karyotype. This case may serve as a paradigmatic example of clonal hematopoietic progression in a patient undergoing CAR-T cell therapy, especially in the context of a TP53 -mutated clone.

Obstructive sleep apnea (OSA) is a chronic, sleep-related breathing disorder. It is characterized by a nocturnal periodic decrease or complete stop in airflow due to partial or total collapse of the oropharyngeal tract. Surgical treatment of OSA is constantly evolving and improving, especially with the implementation of new technologies, and this is needed because of the very heterogeneous reasons for OSA due to the multiple sites of potential airway obstruction. Moreover, all of these surgical methods have advantages and disadvantages; hence, patients should be approached individually, and surgical therapies should be chosen carefully. Furthermore, while it is well-established that oromaxillofacial surgery (OMFS) provides various surgical modalities for treating OSA both in adults and children, a new aspect is emerging regarding the possibility that some of the surgeries from the OMFS domain are also causing OSA. The latest studies are suggesting that surgical treatment in the head and neck region for causes other than OSA could possibly have a major impact on the emergence of newly developed OSA, and this issue is still very scarcely mentioned in the literature. Both oncology, traumatology, and orthognathic surgeries could be potential risk factors for developing OSA. This is an important subject, and this review will focus on both the possibilities of OMFS treatments for OSA and on the OMFS treatments for other causes that could possibly be triggering OSA.

Accumulating data suggest that various neurologic manifestations are reported in critically-ill COVID-19 patients. Although low testosterone levels were associated with poor outcomes, the relationship between testosterone levels and indices of brain injury are still poorly understood. Therefore, we aimed to explore whether testosterone levels are associated with glial fibrillary acidic protein (GFAP) and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), biomarkers of brain injury, in patients with a severe form of COVID-19. The present study was conducted on 65 male patients aged 18−65 with severe COVID-19. Blood samples were collected at three time points: upon admission to ICU, 7 days after, and 14 days after. In patients with neurological sequels (n = 20), UCH-L1 serum concentrations at admission were markedly higher than in patients without them (240.0 (155.4−366.4) vs. 146.4 (92.5−243.9) pg/mL, p = 0.022). GFAP concentrations on admission did not differ between the groups (32.2 (24.2−40.1) vs. 29.8 (21.8−39.4) pg/mL, p = 0.372). Unlike GFAP, UCH-L1 serum concentrations exhibited a negative correlation with serum testosterone in all three time points (r = −0.452, p < 0.001; r = −0.430, p < 0.001 and r = −0.476, p = 0.001, respectively). The present study suggests that the traumatic brain injury biomarker UCH-L1 may be associated with neurological impairments seen in severe COVID-19. Moreover, a negative correlation between UCH-L1 and serum testosterone concentrations implies that testosterone may have a role in the development of neurological sequels in critically-ill COVID-19 patients.

In recent years, sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated beneficial renoprotective effects, which culminated in the recent approval of their use for patients with chronic kidney disease (CKD), following a similar path to one they had already crossed due to their cardioprotective effects, meaning that SGLT2i represent a cornerstone of heart failure therapy. In the present review, we aimed to discuss the pathophysiological mechanisms operating in CKD that are targeted with SGLT2i, either directly or indirectly. Furthermore, we presented clinical evidence of SGLT2i in CKD with respect to the presence of diabetes mellitus. Despite initial safety concerns with regard to euglycemic diabetic ketoacidosis and transient decline in glomerular filtration rate, the accumulating clinical data are reassuring. In summary, although SGLT2i provide clinicians with an exciting new treatment option for patients with CKD, further research is needed to determine which subgroups of patients with CKD will benefit the most, and which the least, from this therapeutical option.

The "commando operation" is an extensive surgical procedure used to treat patients with oral squamous carcinoma and metastasis in the cervical lymph nodes. While the procedure can be curative, it is also very mutilating, which consequently has a major impact on the patient's quality of life. Several studies showed that the procedure is associated with loss of certain functions, such as impairments in speech, chewing, swallowing, and loss of taste and appetite. Furthermore, some of these impairments and their degree depend on the reconstruction method. However, the data regarding the functional impairments and aesthetic results in patients who underwent the "commando operation" along with the pectoralis major myocutaneus flap reconstruction are still inconclusive. This study included 34 patients that underwent partial glossectomy, ipsilateral modified radical neck dissection, pectoralis major myocutaneus flap reconstruction, and adjuvant radiotherapy. A structured questionnaire was used to evaluate aesthetical results and functional impairments as well as to grade the level of satisfaction with the functional and aesthetic outcomes both by the patients and by the operator. Most of the patients stated that their speech ( N = 33; 97%) and salivation ( N = 32; 94.2%) severely changed after the operation and that they cannot chew ( N = 33; 97%) and swallow ( N = 33; 97%) the same as before the operation. Moreover, almost half of the patients ( N = 16; 47%) reported that they have severe sleep impairments. However, only few of the included patients stated that they sought professional help regarding the speech ( N = 4; 11.7%), eating ( N = 5; 14.7%), and sleeping ( N = 4; 11.7%) disturbances. Additionally, there was a statistically significant difference between the operator and the patients in the subjective assessment of the aesthetic results ( p = 0.047), as operators gave significantly better grades. Our results imply that this procedure and reconstructive method possibly cause impairments that have an impact on the patients' wellbeing. Moreover, our outcomes also suggest that patients should be educated and rehabilitated after the "commando operation" since most of them were reluctant to seek professional help regarding their impairments. Lastly, sleep deficiency, which was observed after the procedure, should be further explored.

Catestatin is a pleiotropic peptide with a wide range of immunomodulatory effects. Considering that patients with a severe COVID-19 infection have a major immunological dysregulation, the aim of this study was to evaluate catestatin levels in patients with COVID-19 treated in the intensive care unit (ICU) and to compare them between the fatal and non-fatal outcomes. The study included 152 patients with severe COVID-19, out of which 105 had a non-fatal outcome and 47 had a fatal outcome. Serum catestatin levels were estimated by an enzyme-linked immunosorbent assay in a commercially available diagnostic kit. The results show that catestatin levels were significantly lower in the fatal group compared to the non-fatal group (16.6 ± 7.8 vs. 23.2 ± 9.2 ng/mL; p < 0.001). Furthermore, there was a significant positive correlation between serum catestatin levels and vitamin D levels (r = 0.338; p < 0.001) while there was also a significant positive correlation between serum catestatin levels and growth differentiation factor-15 (GDF-15) levels (r = −0.345; p < 0.001). Furthermore, multivariate logistic regression showed that catestatin, GDF-15 and leukocyte count were significant predictors for COVID-19 survival. These findings imply that catestatin could be playing a major immunomodulatory role in the complex pathophysiology of the COVID-19 infection and that serum catestatin could also be a predictor of a poor COVID-19 outcome.

Purpose: Orthorexia nervosa (ON) is an eating behavior where patients obsessively try to reach health through "purity" of food. Narcissism is a personality trait characterized with the self-belief of grandiosity, importance and need of appreciation. Both of these conditions are connected through self-image in way of reaching perfection through health and body image, whereas one of the ways for reaching it is exercising. This cross-sectional study aimed to investigate ON and its possible association with narcissism in fitness center users., Methods: The study included 1017 fitness center users and three questionnaires were used for the assessment: general information, ORTO-R and Narcissistic personality inventory-13 (NPI-13)., Results: There was a significant negative correlation (r = - 0.467, p < 0.001) between the ORTO-R score and the NPI-13 score. Comparison of the ORTO-R score between different durations of using a fitness center showed statistically significant differences (H = 134.72, p < 0.001). The subjects who are using the fitness center for less than 1 year have the highest ORTO-R score, while those who are using it 1-3 years have the lowest ORTO-R score. Moreover, multiple linear regression showed that ORTO-R score retained significant association with NPI-13 (β ± SE, - 0.416 ± 0.026, p < 0.001) and the duration of using a fitness center (0.576 ± 0.068, p < 0.001) after model adjustment for age and BMI., Conclusion: These results are implying that fitness center users could possibly be vulnerable of developing ON and that there is a strong association between ON and narcissism in this population. However, future larger-scale longitudinal studies are needed to address these findings., Level of Evidence: Level V, cross-sectional survey-based study., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Local random skin flaps and skin grafts are everyday surgical techniques used to reconstruct skin defects. Although their clinical advantages and disadvantages are well known, there are still uncertainties with respect to their long-term results. Hence, the aim of this study was to evaluate outcomes more than one-year post operatively using objective measurement devices. The study included 31 facial defects reconstructed with local random flap, 30 facial defects reconstructed with split-thickness skin grafts (STSGs) and 30 facial defects reconstructed with full-thickness skin grafts (FTSGs). Skin quality was objectively evaluated using MP6 noninvasive probes (Courage + Khazaka GmbH, Cologne, Germany), which measure melanin count, erythema, hydration, sebum, friction and transepidermal water loss. The results showed that there were no significant differences in melanin count, erythema, hydration, sebum level, friction value and transepidermal water loss (TEWL) between the site reconstructed with random local flaps and the same site on the healthy contralateral side of the face. However, both FTSGs and STSGs showed significantly higher levels in terms of TEWL and erythema, whereas the levels of hydration, sebum and friction were significantly lower compared to the healthy contralateral side. Moreover, STSGs resulted in a significant difference in melanin count. These findings imply that the complex pathophysiology of the wound-healing process possibly results in better skin-quality outcomes for random local flaps than skin autografts. Consequently, this suggests that random local flaps should be implemented whenever possible for the reconstruction of facial region defects.

Catestatin (CST) is an important peptide that influences various inflammatory diseases. Our goal was to investigate CST concentrations in patients with RA compared to healthy subjects. This cross-sectional observational study included 80 patients with RA and 80 healthy control subjects. Demographic characteristics and laboratory parameters were recorded. Serum CST levels were determined by an enzyme-linked immunosorbent assay (ELISA). Serum CST levels were significantly higher in RA patients than in the control group (10.53 ± 3.90 vs 5.24 ± 2.37 ng/mL, p < 0.001). In RA patients, there was a statistically significant correlation between CST and patient age (r = 0.418, p < 0.001) and both DAS28 (r = 0.469, p < 0.001) and HAQ scores (r = 0.483, p < 0.001). There was a statistically significant correlation between serum CST levels and RA duration (r = 0.583, p < 0.001). Multiple linear regression analysis showed that serum CST levels retained a significant association with RA duration (β ± SE, 0.13 ± 0.04, p = 0.002) and DAS28 score (0.94 ± 0.45, p = 0.039) after model adjustment for age, body mass index (BMI) and HAQ score, with serum CST levels as a dependent variable. These findings imply that CST is possibly associated with RA complex pathophysiology and disease activity. However, future larger multicentric longitudinal studies are necessary to define the role of CST in RA., (© 2022. The Author(s).)

With the rising global burden of inflammatory bowel disease (IBD) and the rising costs of novel biological drugs, there is an increasing need for dietary approaches and functional foods that could modulate the course of IBD. The Mediterranean diet has proven to be efficacious in managing chronic inflammatory diseases, and recent studies have also shown its benefits in the setting of IBD. Since olive oil and its compounds have been shown to provide a considerable anti-inflammatory effect, in this review, we aim to discuss the latest evidence concerning the impact of olive oil and its bioactive compounds on IBD. Numerous preclinical studies have exhibited solid evidence on the mechanisms by which polyphenol-rich extra-virgin olive oil (EVOO) or specific polyphenols like hydroxytyrosol (HT) provide their anti-inflammatory, antioxidative, antitumour, and microbiota-modulation effects. Accordingly, several human studies that explored the effects of olive oil on patients with IBD further confirmed the evidence brought forward by preclinical studies. Nevertheless, there is a need for larger-scale, multicentric, randomized control trials that would finally elucidate olive oil's level of efficacy in modulating the course of IBD.

Adropin is a secretory protein that mainly modulates metabolic homeostasis and endothelial function. There is growing evidence supporting association of adropin with various inflammatory diseases, including rheumatoid arthritis (RA). This study aimed to compare serum adropin levels between 70 patients with RA and 70 matched healthy controls. Furthermore, we explored adropin correlations with RA disease activity, glucose metabolism parameters and inflammatory biomarkers. Serum adropin levels were determined by a competitive enzyme-linked immunosorbent assay. Serum adropin levels were significantly lower in RA patients than in the control group (2.85 ± 0.91 vs. 4.02 ± 0.99 ng/mL, p < 0.001). In the RA group, serum adropin levels had a significant negative correlation with total cholesterol (r = -0.172, p = 0.043), HbA1c (r = -0.406, p < 0.001), fasting glucose (r = -0.377, p < 0.001) and HOMA-IR (the homeostasis model assessment-estimated insulin resistance; (r = -0.315, p = 0.008)). Multiple linear regression analysis showed that serum adropin levels retained a significant association with levels of fasting glucose (β ± SE, -0.450 ± 0.140, p = 0.002) and HbA1c (-0.528 ± 0.223, p = 0.021) after model adjustments. These findings imply that adropin could have an impact on metabolic homeostasis in RA, although further well-designed studies are warranted in order to establish this.

Metabolic syndrome (MetS) represents a cluster of metabolic abnormalities that includes hypertension, central obesity, insulin resistance, and atherogenic dyslipidemia. Due to the high prevalence (around 1/3 of the world population) economic burden of MetS, there is a need for new dietary, lifestyle, and therapeutic options. Recently, fasting emerged as a dietary method proposed for controlling metabolic risk factors. Intermittent fasting (IF), or time-restricted feeding (TRF), describes an array of feeding patterns in which calorie intake is restricted to a specific time period. Hence, this review aimed to elucidate the latest data on MetS and explore the viability of simple management options, such as IF and TRF. Preclinical studies have shown how IF/TRF exerts beneficial effects on the gut microbiota, glucose and insulin metabolism, weight and visceral fat, and lipid metabolism. However, the results obtained from human studies are somewhat conflicting, as weight loss was achieved in all studies, whereas in some studies, there was no significant effect on insulin resistance, cholesterol/lipid metabolism, or blood pressure. Nevertheless, as only very few human studies were performed, there is a need for more randomized control trials on larger cohorts of patients with MetS to gather higher-yield evidence to clarify whether IF/TRF are suitable dietary patterns for this population.

Family physicians (FPs) are exposed to high amounts of stress, and could be susceptible to the development of mental health disorders (MHD), especially after the emergence of the COVID-19 pandemic. The aim of the current study was to assess MHD history, attitudes toward MHDs and stress-coping strategies in FPs. An additional goal was to estimate their comprehensive well-being and investigate connections with resilience and a healthy lifestyle. A total of 483 FPs submitted their responses via online survey. MHD attitudes were assessed with the according questionnaires, while burnout levels, healthy lifestyle, resilience, job and life satisfaction were estimated with validated scales. Results have shown that 32.5% of FPs disclosed positive MHD history, while 68.7% used professional help. Resilience and healthy lifestyle levels were significantly higher in MHD negative FPs ( p < 0.001), while burnout levels were lower ( p < 0.001). Moreover, healthy lifestyle (β = 0.03, p < 0.001) was an independent correlate of resilience, while healthy lifestyle (β = -0.35, p < 0.001, and resilience (β = -1.82, p < 0.001) were of burnout levels. Finally, resilience (OR = 0.387, p < 0.001) and healthy lifestyle (OR = 0.970, p = 0.021) were shown as independent predictors of positive MHD history status. Strong promotion and education of FP population regarding resilience and healthy lifestyle should be utilized in practice in order to alleviate the possibility of mental health disturbances and the according consequences.

Among many lifestyle components that professional athletes have to follow, nutrition is gradually growing to be one of the key factors for achieving and maintaining optimal sport performance. The Mediterranean diet (MD) is recognized as one of the healthiest dietary patterns worldwide; however, data regarding adherence to the MD among professional athletes are still scarce. Moreover, with the imposed need for a healthy diet among professional athletes, orthorexia nervosa (ON) could become a rising issue. This cross-sectional study included 150 professional athletes and 150 matched recreational athletes from Croatia. Four questionnaires were used for the assessment: general information, a test for the diagnosis of ON (ORTO-15), the International Physical Activity Questionnaire (IPAQ) and the Mediterranean Diet Serving Score (MDSS). Significantly more professional athletes were adherent to the MD ( p < 0.001) and had a tendency to ON ( p < 0.001). Moreover, there was a significant negative correlation between the ORTO-15 score and the total MET min/week score (r = -0.524, p < 0.001) and a significant positive correlation between the MDSS score and the total MET min/week score in the professional athlete group (r = 0.478, p < 0.001). All of these results imply that professional athletes are more concentrated on their dietary patterns than recreational athletes, and that due to this dedication, they possibly have a higher adherence to the MD but also possibly a higher risk for developing ON. However, the association between ON and the MD should be further addressed in the future.

As early commencement of inflammatory bowel disease (IBD) treatment has been shown to substantially improve outcomes, it is of utmost importance to make a timely diagnosis of this disease. Despite undisputed sensitivity of fecal calprotectin, the most widely accepted IBD biomarker, in discriminating between irritable bowel syndrome (IBS) and IBD, as well as recognized role in monitoring disease activity and response to therapy, perhaps the biggest setback of calprotectin use in IBD is lack of specificity. Therefore, an additional biomarker in IBD is warranted. B-cell activating factor (BAFF), a member of the tumor necrosis factor (TNF) superfamily, recently emerged as a viable candidate for this role. So far, overproduction of BAFF has been observed in various autoimmune diseases, most notably in systemic lupus erythematosus, where BAFF-inhibitor belimumab was approved for treatment. As BAFF levels were also shown to correlate with indices of IBD, in this review we aimed to summarize the current evidence with respect to the role of BAFF in diagnosis and assessing the activity of IBD, as well as putative therapeutic implications that may arise from exploring of this relation.

The digestive system is one of the most common sites of malignancies in humans. Since gastrointestinal tumors represent a massive global health burden both in terms of morbidity and health care expenditures, scientists continuously develop novel diagnostic and therapeutic methods to ameliorate the detrimental effects of this group of diseases. Apart from the well-established role of the endoscopic ultrasound (EUS) in the diagnostic course of gastrointestinal and hepatobiliary malignancies, we have recently become acquainted with a vast array of its therapeutic possibilities. A multitude of previously established, evidence-based methods that might now be guided by the EUS emerged: Radiofrequency ablation, brachytherapy, fine needle injection, celiac plexus neurolysis, and endoscopic submucosal dissection. In this review we endeavored to provide a comprehensive overview of the role of these methods in different malignancies of the digestive system, primarily in the treatment and symptom control in pancreatic cancer, and additionally in the management of hepatic, gastrointestinal tumors, and pancreatic cysts., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Accounting for almost one-third of the global mortality, cardiovascular diseases (CVDs) represent a major global health issue. Emerging data suggest that most of the well-established mechanistic explanations regarding the cardiovascular pathophysiology are flawed, and cannot fully explain the progression and long-term effects of these diseases. On the other hand, dysregulation of the sympathetic nervous system (SNS) has emerged as an important player in the pathophysiology of CVDs. Even though upregulated SNS activity is an essential compensatory response to various stress conditions, in the long term, it becomes a major contributor to both cardiac dysfunction and vascular damage. Despite the fact that the importance of SNS hyperactivity in the setting of CVDs has been well-appreciated, its exact quantification and clinical application in either diagnostics or therapy of CVDs is still out of reach. Nevertheless, in recent years a number of novel laboratory biomarkers implicated in the pathophysiology of SNS activation have been explored. Specifically, in this review, we aimed to discuss the role of catestatin, a potent physiological inhibitor of catecholamine spillover that offers cardioprotective effects. Limited data indicate that catestatin could also be a reliable indirect marker of SNS activity and it is likely that high CST levels reflect advanced CV disease burden. Consequently, large-scale studies are required to validate these observations in the upcoming future.

Background: In recent years, American Diabetes Association started to strongly advocate the Mediterranean diet (MD) over other diets in patients with diabetes mellitus (DM) because of its beneficial effects on glycemic control and cardiovascular (CV) risk factors. Tissue levels of advanced glycation endproducts (AGEs) emerged as an indicator of CV risk in DM. Skin biopsy being invasive, the use of AGE Reader has been shown to reflect tissue AGEs reliably., Aim: To examine the association between adherence to MD and AGEs in patients with DM type II., Methods: This cross-sectional study was conducted on 273 patients with DM type II. A survey questionnaire was composed of 3 separate sections. The first part of the questionnaire included general data and the habits of the participants. The second part aimed to assess the basic parameters of participants' diseases and associated conditions. The third part of the questionnaire was the Croatian version of the 14-item MD service score (MDSS). AGEs levels and associated CV risk were measured using AGE Reader (DiagnOptics Technologies BV, Groningen, The Netherlands)., Results: A total of 27 (9.9%) patients fulfilled criteria for adherence to MD, with a median score of 8.0 (6.0-10.0). Patients with none/limited CV risk had significantly higher percentage of MD adherence in comparison to patients with increased/definite CV risk (15.2% vs 6.9%, P = 0.028), as well as better adherence to guidelines for nuts (23.2% vs 12.6%, P = 0.023) and legumes (40.4% vs 25.9%, P = 0.013) consumption. Higher number of patients with glycated hemoglobin (HbA1c) < 7% adhered to MD when compared to patients with HbA1c > 7% (14.9% vs 7.3%, P = 0.045). Moreover, those patients followed the MDSS guidelines for eggs (33.0% vs 46.8%, P = 0.025) and wine (15.6% vs 29.8%, P = 0.006) consumption more frequently. MDSS score had significant positive correlation with disease duration ( r = 0.179, P = 0.003) and negative correlation with body mass index (BMI) values ( r = -0.159, P = 0.008). In the multiple linear regression model, BMI (β ± SE, -0.09 ± 0.04, P = 0.037) and disease duration (β ± SE, 0.07 ± 0.02, P < 0.001) remained significant independent correlates of the MDSS score. Patients with HbA1c > 7% think that educational programs on nutrition would be useful for patients in significantly more cases than patients with HbA1c < 7% (98.9% vs 92.6%, P = 0.009)., Conclusion: Although adherence to MD was very low among people with diabetes, we demonstrated that adherence to MD is greater in patients with lower CV risk, longer disease duration, and well-controlled glycaemia., Competing Interests: Conflict-of-interest statement: There are no conflicts of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

The Mediterranean diet (MD) is based on the traditional cuisine of south European countries, and it is considered one of the healthiest dietary patterns worldwide. The promotion of combined MD and physical activity has shown major benefits. However, the association between physical activity and the MD in regular fitness center users is still insufficiently investigated. This cross-sectional survey-based study was conducted on 1220 fitness center users in Croatia. The survey consisted of three parts: general information, the Mediterranean Diet Serving Score (MDSS) and the International Physical Activity Questionnaire Short Form (IPAQ-SF). The results showed that 18.6% of fitness center users were adherent to the MD, and there was a significant positive correlation between the level of physical activity and the MDSS score (r = 0.302, p < 0.001). Moreover, after dividing the sample into tertiles based on the IPAQ-SF score, the third tertile (MET > 3150 min/wk) had the most fitness center users (34.4%) adherent to the MD, while the first tertile (MET < 1750 min/wk) had the least (6.1%). These outcomes emphasize the importance of physical activity as they imply that, with higher levels of physical activity, people are also possibly more aware of the importance that a healthy and balanced diet has on their well-being.

Although a large amount of data supports the crucial role of endothelial dysfunction (ED) in cardiovascular diseases (CVDs), there is a large bench-to-bedside chasm between basic and clinical research of ED, limiting the implementation of these findings in everyday clinical settings. Hence, it is important to further investigate the pathophysiological mechanisms underlying ED and find modalities that will alleviate its clinical implementation. Adropin, a highly conserved peptide hormone secreted primarily by the liver, recently emerged as an important regulatory component of the vascular endothelium. Specifically, the vasoprotective role of adropin is achieved mainly by affecting endothelial NO synthesis. Thus, in this review, we aimed to summarize the current knowledge regarding the role of adropin in physiological processes and address the protective role of adropin in endothelium with consequent implications to CV pathologies. We focused on data regarding the role of adropin in the clinical setting, with concurrent implications to future clinical use of adropin. Studies suggest that plasma levels of adropin correlate with indices of ED in various pathologies and enhanced disease progression, implying that adropin may serve as a useful biomarker of ED in the upcoming future. On the other hand, despite notable results with respect to therapeutic potential of adropin in preliminary experiments, further well-designed studies are warranted in order to establish if adropin might be beneficial in this setting.

Background: Patients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII., Aim: To determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters., Methods: This cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn's disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn's Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer's instructions., Results: IBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn's disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels ( r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins ( r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic ( r = 0.387, P = 0.005) and diastolic ( r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity ( r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn's Disease ( r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (β ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030)., Conclusion: It is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies., Competing Interests: Conflict-of-interest statement: There are no conflict of interest to report., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

With the rising prevalence of Inflammatory bowel disease (IBD) worldwide, and the rising cost of treatment with novel biological drugs, there is an increasing interest in various diets and natural foods as a potential way to control/modulate IBD. As recent data indicates that diet can modify the metabolic responses essential for the resolution of inflammation, and as wine compounds have been shown to provide substantial anti-inflammatory effect, in this review we aimed to discuss the current evidence concerning the impact of biological compounds present in wine on IBD. A number of preclinical studies brought forth strong evidence on the mechanisms by which molecules in wine, such as resveratrol or piceatannol, provide their anti-inflammatory, anti-oxidative, anti-tumor, and microbiota-modulation effects. However, concerning the effects of alcohol, it is still unclear how the amount of ethanol ingested within the framework of moderate wine consumption (1-2 glasses a day) affects patients with IBD, as human studies regarding the effects of wine on patients with IBD are scarce. Nevertheless, available evidence justifies the conductance of large-scale RCT trials on human subjects that will finally elucidate whether wine can offer real benefits to the IBD population.

Coronary artery disease (CAD) is widely recognized as one of the most important clinical entities. In recent years, a large body of accumulated data suggest that coronary artery calcification, a process highly prevalent in patients with CAD, occurs via well-organized biologic processes, rather than passively, as previously regarded. Matrix Gla protein (MGP), a vitamin K-dependent protein, emerged as an important inhibitor of both intimal and medial vascular calcification. The functionality of MGP hinges on two post-translational modifications: phosphorylation and carboxylation. Depending on the above-noted modifications, various species of MGP may exist in circulation, each with their respective level of functionality. Emerging data suggest that dysfunctional species of MGP, markedly, dephosphorylated-uncarboxylated MGP, might find its application as biomarkers of microvascular health, and assist in clinical decision making with regard to initiation of vitamin K supplementation. Hence, in this review we summarized the current knowledge with respect to the role of MGP in the complex network of vascular calcification with concurrent inferences to CAD. In addition, we discussed the effects of warfarin use on MGP functionality, with concomitant implications to coronary plaque stability.