Factors Affecting the Efficiency of Near-Infrared Indocyanine Green (NIR/ICG) in Lymphatic Mapping for Colorectal Cancer: A Systematic Review.

As laparoscopy gained global popularity in oncologic surgery, the challenge of detecting lymph nodes spurred researchers to explore innovative techniques and approach the situation from a fresh perspective. While many proposed methods have faded into obscurity, the utilization of indocyanine green (ICG) in the surgical treatment of oncologic patients has continued to advance. The immense potential of this dye is widely acknowledged, yet its full extent and limitations in lymphatic mapping for colorectal cancer remain to be precisely determined. This article aims to assess the magnitude of its potential and explore the constraints based on insights from clinical studies published by pioneering researchers. A systematic review of the existing literature, comprising articles in English, was conducted using the Scopus, PubMed, and Springer Link databases. The search employed keywords such as "colorectal cancer" AND/OR "indocyanine green," "fluorescence" AND/OR "lymphatic mapping" AND/OR "lymph nodes." Initially identifying 129 articles, the application of selection criteria narrowed down the pool to 10 articles, which served as the primary sources of data for our review. Despite the absence of a standardized protocol for the application of ICG in colorectal cancer, particularly in the context of lymphatic mapping, the detection rates have exhibited considerable variation across studies. Nevertheless, all authors unanimously regarded this technique as beneficial and promising. Additionally, it is advocated as an adjunctive tool to enhance the accuracy of cancer staging. Near-infrared (NIR)-enhanced surgery holds the promise of transforming the landscape of oncologic surgery, emerging as a valuable tool for surgeons. However, the absence of a standardized technique and the subjective nature of result assessment impose limitations on the potential of this method. Consequently, it can be inferred that the establishment of a universally accepted protocol, encompassing parameters such as dose, concentration, technique, and site of administration of ICG, along with the optimal time needed for fluorescence visualization, would enhance the outcomes. Emphasizing the accurate selection of patients is crucial to prevent the occurrence of false-negative results.

Discharge protocol in acute pancreatitis: an international survey and cohort analysis.

There are several overlapping clinical practice guidelines in acute pancreatitis (AP), however, none of them contains suggestions on patient discharge. The Hungarian Pancreatic Study Group (HPSG) has recently developed a laboratory data and symptom-based discharge protocol which needs to be validated. (1) A survey was conducted involving all members of the International Association of Pancreatology (IAP) to understand the characteristics of international discharge protocols. (2) We investigated the safety and effectiveness of the HPSG-discharge protocol. According to our international survey, 87.5% (49/56) of the centres had no discharge protocol. Patients discharged based on protocols have a significantly shorter median length of hospitalization (LOH) (7 (5;10) days vs. 8 (5;12) days) p < 0.001), and a lower rate of readmission due to recurrent AP episodes (p = 0.005). There was no difference in median discharge CRP level among the international cohorts (p = 0.586). HPSG-protocol resulted in the shortest LOH (6 (5;9) days) and highest median CRP (35.40 (13.78; 68.40) mg/l). Safety was confirmed by the low rate of readmittance (n = 35; 5%). Discharge protocol is necessary in AP. The discharge protocol used in this study is the first clinically proven protocol. Developing and testifying further protocols are needed to better standardize patients' care.

The Effects of Cardioprotective Antidiabetic Therapy on Microbiota in Patients with Type 2 Diabetes Mellitus-A Systematic Review.

As the pathophysiologic mechanisms of type 2 diabetes mellitus (T2DM) are discovered, there is a switch from glucocentric to a more comprehensive, patient-centered management. The holistic approach considers the interlink between T2DM and its complications, finding the best therapies for minimizing the cardiovascular (CV) or renal risk and benefitting from the treatment's pleiotropic effects. Sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RA) fit best in the holistic approach because of their effects in reducing the risk of CV events and obtaining better metabolic control. Additionally, research on the SGLT-2i and GLP-1 RA modification of gut microbiota is accumulating. The microbiota plays a significant role in the relation between diet and CV disease because some intestinal bacteria lead to an increase in short-chain fatty acids (SCFA) and consequent positive effects. Thus, our review aims to describe the relation between antidiabetic non-insulin therapy (SGLT-2i and GLP-1 RA) with CV-proven benefits and the gut microbiota in patients with T2DM. We identified five randomized clinical trials including dapagliflozin, empagliflozin, liraglutide, and loxenatide, with different results. There were differences between empagliflozin and metformin regarding the effects on microbiota despite similar glucose control in both study groups. One study demonstrated that liraglutide induced gut microbiota alterations in patients with T2DM treated initially with metformin, but another failed to detect any differences when the same molecule was compared with sitagliptin. The established CV and renal protection that the SGLT-2i and GLP-1 RA exert could be partly due to their action on gut microbiota. The individual and cumulative effects of antidiabetic drugs on gut microbiota need further research.

Role of glutathione-S-transferase gene P1 in the diagnosis of prostate cancer in patients with 'grey level' prostate-specific antigen values.

Prostate cancer (PC) represents the second most frequent cancer diagnosis in men and, at the same time, is one of the top six causes of death worldwide. The aim of the present study was to evaluate the diagnostic value of glutathione-S-transferase gene P1 (GST-P1) in patients that fall within the 'grey area' of the prostate-specific antigen (PSA) values. A retrospective observational study on 80 patients with prostate abnormal volumes and PSA values in the range 4-10 ng/ml was performed. The prostate gland was extracted following transrectal ultrasonography, and GST-P1 gene expression was analysed. A histopathological examination was considered the gold standard for PC diagnosis. Among the 53 patients diagnosed with PC, 69.8% (n=37) were GST-P1-positive, whereas, among the 27 patients diagnosed with benign prostatic hyperplasia, 18.5% (n=5) were GST-P1-positive. The sensitivity for diagnosing PC in patients with PSA values between 4 and 10 ng/ml was 69.81%, and the specificity was 81.48%. The positive predictive value was 88.1% [95% confidence interval (CI), 74.37-96.02%] and the negative predictive value was 57.89% (95% CI, 40.82-73.69%). Collectively, these results show the potential of using GST-P1 gene expression in patients who are suspected of having PC, but where the PSA values are inconclusive.

Benefits of crenotherapy in digestive tract pathology (Review).

Balneotherapy, a branch of physical and rehabilitation medicine using the natural factors of balneal resorts for therapeutical purposes to modulate the symptoms of numerous diseases, represents a non-pharmaceutical therapeutic alternative, easily accepted by patients and used both preventively and curatively. Crenotherapy, a branch of balneotherapy, is the method in which mineral waters are used as a therapeutic internal cure by ingestion. This procedure is performed in spa resorts (where these natural resources exist), and the ingestion of mineral water takes place at the source (spring), in the quantities recommended by the medical rehabilitation physician, according to specific regimens for the condition to be treated. Depending on their physical and chemical composition, the therapeutic mineral waters fall into several categories, having clear indications for certain pathologies. Hypotonic, isotonic, or slightly hypertonic mineral waters are recommended in diseases of the digestive tract and hepatobiliary conditions. Over time, studies have been conducted to determine the effect of these types of treatments, highlighting the complex influence of crenotherapy on the gastrointestinal tract, with favorable results, therefore the use of mineral water intake in various pathologies being recommended. The current review focuses on the existing literature data and refers to the main progress made in understanding the benefit, indications, and crenotherapy procedures in the management of gastrointestinal disorders.

The Role of Endothelium in COVID-19.

The 2019 novel coronavirus, known as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19), is causing a global pandemic. The virus primarily affects the upper and lower respiratory tracts and raises the risk of a variety of non-pulmonary consequences, the most severe and possibly fatal of which are cardiovascular problems. Data show that almost one-third of the patients with a moderate or severe form of COVID-19 had preexisting cardiovascular comorbidities such as diabetes mellitus, obesity, hypertension, heart failure, or coronary artery disease. SARS-CoV2 causes hyper inflammation, hypoxia, apoptosis, and a renin-angiotensin system imbalance in a variety of cell types, primarily endothelial cells. Profound endothelial dysfunction associated with COVID-19 can be the cause of impaired organ perfusion that may generate acute myocardial injury, renal failure, and a procoagulant state resulting in thromboembolic events. We discuss the most recent results on the involvement of endothelial dysfunction in the pathogenesis of COVID-19 in patients with cardiometabolic diseases in this review. We also provide insights on treatments that may reduce the severity of this viral infection.

Tumor microenvironment is not an 'innocent bystander' in the resistance to treatment of head and neck cancers (Review).

Head and neck cancers are still one of the most common types of cancer in the world. They rank in the leading sixth place in terms of incidence globally, and the incidence continues to rise. The mortality rates remain at high levels. Pathological subclassification places squamous cell carcinoma of the head and neck (HNSCC) in the first place concerning the histological forms of head and neck cancers; a tumor with extremely aggressive behavior and high mortality rates. The tumor microenvironment is a very complex ecosystem of cellular and non-cellular components, characterized by unique features, that contribute to the appearance of immunosuppression and diminished anticancer immunity, impacting patient prognosis and treatment outcome. Despite many important advances in therapy, resistance to therapy represents a difficult challenge in HNSCC patients. Tumor progression, metastasis, and response to therapy are all influenced by the complex ecosystem represented by the tumor microenvironment and by the interactions between cellular and non-cellular components of this system. Therefore, the tumor microenvironment, in the light of recent data, is not an innocent bystander. In the last few years, there has been a sustained effort to characterize the tumor microenvironment, to identify targets of response and identify other mechanisms of tumor-specific immune responses, or to discover other biomarkers of response. There is an urgent need to understand how to properly select patients, the therapy sequence, and how to use feasible biomarkers that can help to identify the patient who may obtain the most benefit from available therapies.

How specific molecular-targeted agents can make obsolete a 'one size fits all' approach in EGFR-mutated NSCLC treatment (Review).

Despite many advances in the latest period, lung cancer remains the cancer with the highest mortality. The latest developments concerning lung cancer treatment have changed the clinical practice by prolonging patient survival; however, unfortunately, there remains a high mortality rate firstly due to disease aggressivity and secondly through lack of early diagnosis and screening programs. Currently, researchers and clinicians are talking about personalized cancer treatment, and a complete diagnostic evaluation should consider, in addition to staging and histology, molecular aberrations, and genetics of the tumor tissue. The development of tyrosine kinase inhibitors (TKIs) has led to an improvement in survival for patients with EGFR mutations, this being the most studied driver mutation in adenocarcinoma; and at the same time an important predictive factor for patient outcome following the treatment with TKIs. Reseach must investigate the different TKI combination strategies in order to overcome resistance and to increase patient survival. Currently, there are ongoing clinical trials that will probably change the therapeutic approach for EGFR-mutated advanced or metastatic NSCLC patients.

Predictors of spontaneous bacterial peritonitis in Romanian adults with liver cirrhosis: Focus on the neutrophil-to-lymphocyte ratio.

Spontaneous bacterial peritonitis (SBP) is a severe complication of liver cirrhosis whose diagnosis is based on a polymorphonuclear leukocyte (PMN) value >250 mm3, yet this PMN value cannot identify all existing types. The aim of our study was to determine the clinical and biological factors that were associated with SBP and predict its occurrence, focusing on the neutrophil-to-lymphocyte ratio (NLR) as one of them. Our retrospective study included 216 patients with liver cirrhosis who were hospitalized between December 2019 and January 2010 at the Emergency County Clinical Hospital of 'St. Apostle Andrew' in Constanta, Romania. Demographic, clinical, and laboratory data were collected from patient observation sheets. The patients were divided into two groups: One group of patients with SBP and the other without SBP. The diagnosis of SBP was made when patients presented with PMN >250 mm3 and other causes of secondary bacterial peritonitis were excluded. The mean age of the patients was 61.25±10.67 years, and the alcoholic etiology of liver cirrhosis was most common (44%). Univariate logistic regression analysis showed that there was an association between biological parameters, such as serum white blood cells, total platelet count, total bilirubin, serum albumin, international normalized ratio, creatinine, erythrocyte sedimentation rate (ESR), serum sodium, alkaline reserve, and NLR, and clinical parameters, such us upper gastrointestinal bleeding and cardiac comorbidities in the occurrence of SBP. Multivariate analysis identified ESR and NLR as predictive factors in the occurrence of SBP. The area under the curve (AUC) was 0.916 [P<0.001, 95% confidence interval (CI) 0.870-0.949] for ESR and AUC was 0.963 (P<0.001, 95% CI 0.928-0.984) for NLR, respectively. In conclusion, the combination of these 2 biological parameters is useful in identifying or excluding SBP.

Spontaneous bacterial peritonitis mortality trends of cirrhotic patients in the last decade in Constanta County.

Spontaneous bacterial peritonitis (SBP) is a complication of liver cirrhosis with an increased in-hospital mortality rate. For this reason, the aim of the present study was to examine the main predictors of mortality in order to be able to identify high-risk patients in time and to guide the optimal treatment for prognosis improvement. We retrospectively collected demographic, clinical, laboratory and treatment data as well as data regarding length of stay and cost of hospitalization from 72 patients diagnosed with SBP between January 2010 and December 2019 in the Emergency Clinical Hospital St. Apostle Andrew, Constanta, Romania. Patients were divided into two groups: Those who survived and those who died. Logistic regression was used to identify a possible association between these factors and the increased risk of mortality. Univariate analysis revealed that clinical factors (fever, chills, and hepatic encephalopathy), biological factors such as serum and ascites leukocyte value, polymorphonuclear percentage (PMN), erythrocyte sedimentation rate (ESR) value, previous SBP episodes, and the presence of complications such as acute kidney injury (AKI), sepsis, and systemic inflammatory response syndrome (SIRS) were significantly associated with in-hospital mortality in patients with SBP. Multivariate analysis revealed that SIRS (P=0.0010) and fever (P=0.0258) were significantly associated with in-hospital mortality in patients with SBP. Findings of the present study suggest that, SIRS and fever were independent predictive factors of mortality in cirrhotic patients with SBP.

Overexpression of Survivin-1, TAG-72 and HERC5 in patients diagnosed with hepatocellular carcinoma in the Black Sea coast geographical area.

Epidemiological data regarding hepatocellular carcinoma (HCC) report unsatisfactory morbimortality rates despite the global efforts to decrease the incidence and prolong patient survival. Current guidelines lack diagnostic biomarkers to better characterize patients with HCC. We aimed to validate the overexpression of Survivin-1, tumor-associated glyocoprotein 72 (Tag-72), and HECT and RLD domain containing E3 ubiquitin protein ligase 5 (HERC5) as tissue biomarkers for HCC characterization in patients from our geographical area and to standardize a local biomarker panel to be introduced in the current management guideline. Thirty samples of histologically confirmed HCC were compared to an equal number of samples of benign tumors in terms of Survivin-1, TAG-72, and HERC5 overexpression. Student's t-test, Mann-Whitney U test and Chi-square test were used to find differences between the two studied groups and to compare the categorical variables. The discriminative power of Survivin-1, Tag-72, and HERC5 overexpression was assessed using ROC curves. The multivariate linear regression analysis revealed that Survivin, Tag-72, and HERC5 were significantly overexpressed in older male patients, with α-fetoprotein (AFP) >200 ng/dl, low serum albumin, as well as in patients with imaging features of portal thrombosis and ascites. The diagnostic performance of Survivin-1, Tag-72 and HERC5 tissue biomarkers for HCC characterization was superior to that of the gold-standard AFP. Our study results validate the overexpression of Survivin-1, Tag-72, and HERC5 as tissue biomarkers for HCC characterization in patients from our geographical region and could be standardized in the current HCC management guideline.

Thrombosis and Haemostasis challenges in COVID-19 - Therapeutic perspectives of heparin and tissue-type plasminogen activator and potential toxicological reactions-a mini review.

The coronavirus disease (COVID)-19 pandemic is a major challenge for the health systems worldwide. Acute respiratory distress syndrome (ARDS), is one of the most common complications of the COVID-19 infection. The activation of the coagulation system plays an important role in the pathogenesis of ARDS. The development of lung coagulopathy involves thrombin generation and fibrinolysis inhibition. Unfractionated heparin and its recently introduced counterpart low molecular weight heparin (LMWH), are widely used anticoagulants with a variety of clinical indications allowing for limited and manageable physio-toxicologic side effects while the use of protamine sulfate, heparin's effective antidote, has made their use even safer. Tissue-type plasminogen activator (tPA) is approved as intravenous thrombolytic treatment. The present narrative review discusses the use of heparin and tPA in the treatment of COVID-19-induced ARDS and their related potential physio-toxicologic side effects. The article is a quick review of articles on anticoagulation in COVID infection and the potential toxicologic reactions associated with these drugs.

Acute Mesenteric Ischemia in COVID-19 Patients.

Acute mesenteric ischemia is a rare but extremely severe complication of SARS-CoV-2 infection. The present review aims to document the clinical, laboratory, and imaging findings, management, and outcomes of acute intestinal ischemia in COVID-19 patients. A comprehensive search was performed on PubMed and Web of Science with the terms "COVID-19" and "bowel ischemia" OR "intestinal ischemia" OR "mesenteric ischemia" OR "mesenteric thrombosis". After duplication removal, a total of 36 articles were included, reporting data on a total of 89 patients, 63 being hospitalized at the moment of onset. Elevated D-dimers, leukocytosis, and C reactive protein (CRP) were present in most reported cases, and a contrast-enhanced CT exam confirms the vascular thromboembolism and offers important information about the bowel viability. There are distinct features of bowel ischemia in non-hospitalized vs. hospitalized COVID-19 patients, suggesting different pathological pathways. In ICU patients, the most frequently affected was the large bowel alone (56%) or in association with the small bowel (24%), with microvascular thrombosis. Surgery was necessary in 95.4% of cases. In the non-hospitalized group, the small bowel was involved in 80%, with splanchnic veins or arteries thromboembolism, and a favorable response to conservative anticoagulant therapy was reported in 38.4%. Mortality was 54.4% in the hospitalized group and 21.7% in the non-hospitalized group (p < 0.0001). Age over 60 years (p = 0.043) and the need for surgery (p = 0.019) were associated with the worst outcome. Understanding the mechanisms involved and risk factors may help adjust the thromboprophylaxis and fluid management in COVID-19 patients.

Correlation between plasma homocysteine and first myocardial infarction in young patients: Case-control study in Constanta County, Romania.

An elevated level of total plasma homocysteine has been associated with a higher risk of atherosclerosis and coronary heart disease. The aim of our research was to study the relation between homocysteine and myocardial infarction (MI) in young patients. We conducted a case-control study in Constanta County, Romania including 61 patients, divided in two groups. The first group, the MI group, consisted of 28 patients, male (67.9%) and female (32.1%) aged less than 45 years who were consecutively admitted to the Intensive Coronary Care Unit of the Emergency County Hospital of Constanta from September 1, 2017 to August 31, 2018 (12 months), with an established diagnosis of first acute MI. The second group, the control group, included 33 patients, male (75.8%) and female (24.2%) aged less than 45 years, with cardiovascular risk factors and/or stable angina pectoris that were consecutively addressed for ambulatory cardiac evaluation at the Outpatient Clinic of Emergency County Hospital of Constanta during the same period. Fasting plasma homocysteine was determined in both groups, within 24 h after MI onset, respectively after first cardiac exam in the controls. High homocysteine was statistically confirmed to be a risk factor in the study group, especially in association with smoking, chronic kidney disease (CKD), and to a lesser extent with diabetes mellitus (DM) and hypertension. Data analysis was performed using IBM SPSS Statistics 23. The procedures used included descriptive statistics, parametric statistical tests (Independent sample t-test), non-parametric statistical tests [Chi-square test of the association, with the evaluation of odds ratio (OR)]; the significance level used in the analysis (P-value) was 0.05. After adjusting for variables, our study results pointed out a strong association between plasma homocysteine and first acute MI among young patients, emphasising plasma homocysteine as a possible risk factor for myocardial infarction.

Death by SARS-CoV 2: a Romanian COVID-19 multi-centre comorbidity study.

Evidence regarding the relation between SARS-CoV-2 mortality and the underlying medical condition is scarce. We conducted an observational, retrospective study based on Romanian official data about location, age, gender and comorbidities for COVID-19 fatalities. Our findings indicate that males, hypertension, diabetes, obesity and chronic kidney disease were most frequent in the COVID-19 fatalities, that the burden of disease was low, and that the prognosis for 1-year survival probability was high in the sample. Evidence shows that age-dependent pairs of comorbidities could be a negative prognosis factor for the severity of disease for the SARS-CoV 2 infection.

Possible Influence of Weight Gain and Creatinine Levels in Predicting Response to Nivolumab: A Multicenter Analysis.

BACKGROUND: Literature suggests that high body mass index can be correlated with better response to immune checkpoint inhibitors. On the other hand, sarcopenia seems to be a negative predictive marker. Materials and methods: The present analysis is a retrospective, multicenter trial that included patients with metastatic melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma treated with nivolumab between 2018 and 2020. Patients were stratified by creatinine levels both at treatment initiation and at first follow-up (at three months) and by BMI for the same intervals, as recorded in the patients' charts. Creatinine was considered a surrogate marker for sarcopenia. IBM SPSS version 20 was used for statistical analysis. Results: A total of 57 (n = 57) patients were included in the trial. Overall response rate (ORR) for the entire population was 38.59% (p = 0.02). Patients with BMI lower than 25 had an ORR of 28.5% (p = 0.003), whereas patients with BMI higher than 25 had an ORR of 42.3% (p = 0.002). Patients who gained weight during treatment had a lower probability of having progressive disease (OR = 0.4 [95% CI; 0.4-1.2]), as did patients with creatinine higher than 0.9 (OR = 0.39 [95% CI: 0.13-1.14]). No superiority was found in progression-free survival (PFS) when patients were dichotomized for BMI = 25 or BMI = 18.5. Mean PFS in the BMI under 18.5 group was 10.2 months [95% CI: 5.8-23.1], versus 11.2 for BMI over 18.5 [95% CI: 5.3-25.3], p < 0.03. Mean PFS for the BMI under 25 was 11.2 months [95% CI: 7.2-20.1], vs. 13.3 months [95% CI: 6.4-22] for the BMI over 25, p < 0.001. There were also differences in PFS in the patients with baseline creatinine over 0.9 when compared with under 0.9 values. Mean PFS in the first group was 19.78 months [95% CI: 16.23-22.9] vs. 16.1 [95% CI: 12.2-20.3], p < 0.001. Conclusion: Patients treated with nivolumab who have weight gain during treatment have a better PFS than the ones who do not. Creatinine levels of over 0.9 at treatment initiation also have positive predictive value.

NLRP3 Inflammasome Biomarker-Could Be the New Tool for Improved Cardiometabolic Syndrome Outcome.

Metabolomics, the research area studying chemical processes involving metabolites, finds its utility in inflammasome biomarker discovery, thus representing a novel approach for cardiometabolic syndrome pathogeny acknowledgements. Metabolite biomarkers discovery is expected to improve the disease evolution and outcome. The activation of abundantly expressed NLRP3 inflammasome represents the background process of the diabetes mellitus disturbances like hyperglycemia and insulin resistance, as well as for myocardial cell death and fibrosis, all of them being features characteristic for cardiometabolic syndrome. Many molecules like troponins, brain natriuretic protein (BNP), ST2/IL-33, C-reactive protein (CRP), TNF, IL-1ß, and IL-18 cytokines have been already examined as molecular markers for diagnosing or predicting different cardiac disturbances like myocardial infarction, heart failure, or myocarditis. In addition, metabolomics research comes with new findings arguing that NLRP3 inflammasome becomes a promising molecular tool to use for clinical and therapeutical management providing new targets for therapies in cardiometabolic syndrome. Inflammasome markers analyses, along with other molecular or genetic biomarkers, will result in a better understanding of cardiometabolic syndrome pathogenesis and therapeutic targets. Screening, diagnostic, and prognostic biomarkers resulted from inflammasome biomarker research will become standard of care in cardiometabolic syndrome management, their utility becoming the first magnitude.

Reducing upper digestive bleeding risk in patients treated with direct oral anticoagulants and concomitant infection with Helicobacter pylori.

Direct oral anticoagulants (DOACs) such as apixaban or dabigatran are excellent options in preventing embolic cardiovascular events. Observational studies have shown that gastrointestinal bleeding risks produced by DOACs could be lowered when correcting some host co-factors i.e. Helicobacter pylori (HP) infection. The upper digestive bleeding (UDB) rates in patients with DOAC indication and the usefulness of anti-HP therapy addition were compared. An observational retrospective study was conducted of medical records of 260 patients treated with DOACs, 130 of whom were concomitantly treated for HP infection in accordance with Maastricht V/Florence consensus. The severity of bleeding, the complexity of endoscopic treatment required to stop the bleeding, the re-bleeding rates, the surgical treatment indication and the overall mortality rates were compared between the groups. The risk of UDB was higher in HP-untreated patients in both types of DOACs used (respectively 2.08, 2.02). HP-untreated Forrest Ia/Ib/IIa and IIb DOACs patients had more severe bleedings compared with same class of HP-treated patients (P=0.007/0.005; 0.009/0.006; 0.048/0.005, 0.044/0.049, respectively). Endoscopic treatments such as adrenaline injections combined with metallic clip attachments were more frequently mandatory in HP-untreated DOACs patients for classes Ia/b and IIa (respectively, P=0.000/0.001, P=0.003/0.003). The re-bleeding rates were higher in HP-untreated patients with concomitant DOACs (OR 82.5; 95% CI 30.1-121.7; P=0.005). A history of peptic ulcer or UDB was associated with a 2.9-fold higher risk of UDB in HP-untreated compared with HP-treated patients, slightly increased for dabigatran compared with apixaban (RR 3.06, 2.72, P<0.5, respectively). Surgical intervention and the UDB-related mortality rates were higher in HP-untreated patients (P=0.041/0.044, P=0.007, respectively). HP-eradication treatment and bacterial clearance improve the safety profile of DOACs treatment, especially in fragile patients, in whom the UDB rates can be lowered, and the overall outcome can be enhanced by this combined approach.

Non-alcoholic fatty liver disease: A major challenge in type 2 diabetes mellitus (Review).

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence in type 2 diabetes mellitus (T2DM) patients, being one of the disorders with a relevant global burden. Cross-sectional studies have shown that patients with T2DM and NAFLD have a higher prevalence of liver fibrosis, compared with the general population. Patients with non-alcoholic steatohepatitis (NASH) and T2DM have an increased mortality and morbidity, therefore they generate substantial health care costs. NASH worsens chronic diabetes complications, and T2DM aggravate the NASH progression to fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). The objectives in NAFLD and NASH therapy are to reduce disease activity, to slow down progression of fibrosis, and to lower the risk factors. Unfortunately, there are no specific validated pharmacological therapies. Several trials have demonstrated that anti-diabetic agents such as thiazolidindiones, sodium-glucose co-transporter inhibitors, glucagon like peptide-1 receptor analogs, or dipeptidyl peptidase-4 inhibitors might have complimentary benefits for patients with NAFLD. Some of the effect on reducing steatosis and fibrosis is explained by the weight loss these treatments produce. A goal in standard care is developing screening tools, early and non-invasive diagnosis methods, studying the pleiotropic effects of drugs, together with newer therapeutic agents, which can target mutual pathogenic mechanisms for diabetes and liver disease.

Clinical presentation of a patient with cutis laxa with systemic involvement: a case report.

Cutis laxa (CL) or elastolysis is a rare inherited or acquired connective tissue disorder in which the skin becomes inelastic and hangs loosely in folds (Mitra et al., 2013). The clinical presentation and the type of inheritance show considerable heterogeneity (Shehzad et al., 2010). We aimed to present the atypical case of a young male patient diagnosed at 36-year-old with CL with systemic involvement. The complex medical history, with a suspected but unconfirmed progeria at nine months, repeated lung and urinary infections, complicated inguinoscrotal hernia, prostatic hypertrophy, bilateral entropion, colorectal diverticula and heart failure, suggested a systemic genetic disease, but the absence of family history made the diagnosis of CL difficult. The skin biopsy and the characteristic features discovered during anatomopathological exam made possible the positive and differential diagnosis, creating the link between the various organ involvement and CL diagnosis. Because of the age of our patient, of normal growth and mental development, and negative family history, we suspected an autosomal dominant form of CL with early onset and severe manifestation. Of course, we cannot exclude a recessive form, due to the heterogeneity of this disease.