Acute cholangitis: a state-of-the-art review.

Acute cholangitis is a potentially life-threatening bacterial infection of the intra and/or extrahepatic bile ducts. It remains the second and third cause of community-acquired and hospital-acquired bacteremia, respectively, and is associated with mortality rates of up to 15%, despite advances in broad-spectrum antimicrobial therapy and improved access to emergency biliary tract decompression procedures. Even though not much has changed in recent years in terms of diagnosis or treatment, new data have emerged regarding multidrug-resistant bacteria that serve as etiologic agents of cholangitis. Moreover, different approaches in antibiotic regimes depending on severity grading and bile sample cultures as well as novel minimally invasive endoscopic procedures that can help when consecrated treatments such as endoscopic retrograde cholangiopancreatography (ERCP) fail, cannot be performed, or are unavailable have been proposed. This state-of-the-art review aims to offer a complete and updated assessment of the epidemiology, novel diagnostic and therapeutic methods, complications, and prognostic variables of acute cholangitis. The authors will review the prognostic implications of unusual complications, the relevance of regular bile samples and antibiograms, and their new role in guiding antibiotic therapy and limiting antibiotic resistance to present an organized and comprehensive approach to the care of acute cholangitis.

Diagnostic Challenge in Heterotopic Pancreas in the Ampulla of Vater with Obstructive Jaundice - A Case Report and Literature Review.

Heterotopic pancreas is a rare congenital abnormality. The most common location is the stomach, duodenum and proximal jejunum. Rare locations are represented by the ampulla of Vater, esophagus, ileum, Meckel diverticulum, biliary tract, mesentery and spleen. We present the case of a 49 year old patient investigated for obstructive jaundice and diagnosed with an ampullar heterotopy of pancreas parenchyma, initially considered to be a malignant tumor. A Whipple pancreatoduodenectomy was performed with good postoperative evolution, the serum levels of bilirubin being normal after the first postoperative week.

Overview of dyslipidemia and metabolic syndrome in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) occur due to the abnormal proliferation of one or more terminal myeloid cell lines in peripheral blood. Subjects suffering from MPNs display a high burden of cardiovascular risk factors, and thrombotic events are often the cause of death in this population of patients. Herein, we provide a brief overview of dyslipidemia and metabolic syndrome and their epidemiology in MPNs and examine the common molecular mechanisms between dyslipidemia, metabolic syndrome, and MPNs, with a special focus on cardiovascular risk, atherosclerosis, and thrombotic events. Furthermore, we investigate the impact of dyslipidemia and metabolic syndrome on the occurrence and survival of thrombosis in MPN patients, as well as the management of dyslipidemia in MPNs, and the impact of MPN treatment on serum lipid concentrations, particularly as side/adverse effects reported in the context of clinical trials.

Risk Factors and Prognostic Factors in GBC.

Background: Gallbladder cancer (GBC) is a rare entity with a poor prognosis, usually discovered late due to nonspecific symptoms; therefore, over the last years, attention has been focused on identifying the risk factors for developing this malignancy in order to provide an early diagnosis, as well as new prognostic factors in order to modulate the long-term evolution of such cases. The aim of this review is to discuss both major risk factors and prognostic factors in GBC for a better understanding and integration of relevant and currently available information. Methods: A literature search was performed using Cochrane Library, PubMed, Google Scholar, Elsevier, and Web of Science; studies published after the year of 2000, in English, were reviewed. Results: Over time, risk factors associated with the development of GBC have been identified, which outline the profile of patients with this disease. The most important prognostic factors in GBC remain TNM staging, safety margin, and R0 status, along with perineural invasion and lymphovascular invasion. Both the technique and experience of the surgeons and a pathological examination that ensures final staging are particularly important and increase the chances of survival of the patients. Conclusions: improvements in surgical techniques and pathological analyses might provide better and more consistent guidance for medical staff in the management of patients with GBC.

Assessment of Total Antioxidant Capacity, 8-Hydroxy-2'-deoxy-guanosine, the Genetic Landscape, and Their Associations in BCR::ABL-1-Negative Chronic and Blast Phase Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs), namely, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are clonal stem cell disorders defined by an excessive production of functionally mature and terminally differentiated myeloid cells. MPNs can transform into secondary acute myeloid leukemia (sAML/blast phase MPN) and are linked to alterations in the redox balance, i.e., elevated concentrations of reactive oxygen species and markers of oxidative stress (OS), and changes in antioxidant systems. We evaluated OS in 117 chronic phase MPNs and 21 sAML cases versus controls by measuring total antioxidant capacity (TAC) and 8-hydroxy-2'-deoxy-guanosine (8-OHdG) concentrations. TAC was higher in MPNs than controls (p = 0.03), particularly in ET (p = 0.04) and PMF (p = 0.01). MPL W515L-positive MPNs had higher TAC than controls (p = 0.002) and triple-negative MPNs (p = 0.01). PMF patients who had treatment expressed lower TAC than therapy-free subjects (p = 0.03). 8-OHdG concentrations were similar between controls and MPNs, controls and sAML, and MPNs and sAML. We noted associations between TAC and MPNs (OR = 1.82; p = 0.05), i.e., ET (OR = 2.36; p = 0.03) and PMF (OR = 2.11; p = 0.03), but not sAML. 8-OHdG concentrations were not associated with MPNs (OR = 1.73; p = 0.62) or sAML (OR = 1.89; p = 0.49). In conclusion, we detected redox imbalances in MPNs based on disease subtype, driver mutations, and treatment history.

Two Different Tumors and Lung Aspergilloma: An Uncommon Etiopathogenic Association.

Several cases reported in the literature have confirmed the link between pulmonary aspergillosis and various malignant diseases. Furthermore, it has been observed that the correlation between carcinoid tumor and lung adenocarcinoma is quite uncommon. The etiopathogenic mechanisms underlying these correlations remain poorly defined. We present the case of a patient with three of these diseases: a lung adenocarcinoma with a lepidic pattern, a typical carcinoid, and pulmonary aspergillosis. An additional noteworthy aspect of this case pertains to the timely detection of both lung malignancies. Thus, the necessity for further investigation to ascertain the pathogenic connection among the three diseases is underscored. The ultimate objective is to enhance the prognosis of individuals diagnosed with lung cancer, which is a prevailing malignant disease on a global scale.

Translation, Cultural Adaptation, and Validation into Romanian of the Myeloproliferative Neoplasm Symptom Assessment Form-Total Symptom Score (MPN-SAF TSS or MPN-10) Questionnaire.

Background: Patients with myeloproliferative neoplasms (MPNs) experience a high disease-related symptom burden. A specific instrument to evaluate quality of life (QoL), i.e., the MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS; MPN-10), was developed. We conducted the translation, cultural adaptation, and validation into Romanian of the MPN-10. Methods: We translated the MPN-10 and tested its psychometric properties. Results: We recruited 180 MPN patients: 66 polycythemia vera (36.67%), 61 essential thrombocythemia (33.89%), 51 primary and secondary myelofibrosis (SMF) (28.33%), and 2 MPN-unclassifiable (1.11%). The mean TSS was 19.51 ± 16.51 points. Fatigue, inactivity, and concentration problems were the most cumbersome symptoms. We detected scoring differences between MPN subtypes regarding weight loss (p < 0.001), fatigue (p = 0.006), early satiety (p = 0.007), night sweats (p = 0.047), pruritus (p = 0.05), and TSS (p = 0.021). There were strong positive associations between TSS and inactivity, fatigue, and concentration problems, and moderate negative correlations between QoL scores and all MPN-10 items. Cronbach's α internal consistency coefficient was 0.855. The Kaiser-Meyer-Olkin construct validity test result was 0.870 and the Bartlett Sphericity Test was significant (p < 0.001). Symptom scores were loaded into one single factor according to the exploratory factor analysis. Conclusions: The Romanian MPN-10 version displayed excellent psychometric properties and is a reliable instrument for assessing symptom burden and QoL in Romanian MPN patients.

Ethical implications of developing RNA-based therapies for cardiovascular disorders.

The awareness concerning RNA-based therapies was boosted significantly after the successful development of COVID-19 vaccines. However, they can potentially lead to significant advances in other areas of medicine, such as oncology or chronic diseases. In recent years, there has been an exponential increase in the number of RNA-based therapies that were evaluated as potential treatments for cardiovascular disorders. One of the areas that was not explicitly assessed about these therapies is represented by their overall ethical framework. Some studies evaluate ethical issues of RNA-based treatments in general or targeting specific disorders (especially neurodegenerative) or interventions for developing RNA-based vaccines. Much less information is available regarding the ethical issues associated with developing these therapeutic strategies for cardiovascular disorders, which is the main aim of this study. We will focus our analysis on three main topics: risk-benefit analysis (including the management of public awareness about these technologies), and justice (in both research and clinical medicine).

Recurrence and Carcinogenetic Rates of Colorectal Polyps.

AIM: to determin the recurrence rate of benign recto-colonic polyps in a 5-year interval, and compare the development rate of intrapolypoid carcinomatous lesions in polypectomized versus nonpolypectomized subjects. MATERIAL AND METHOD: a group of 77 patients diagnosed with recto-colonic polypoid lesions during the period 2014-2019 underwent colonoscopy at the time of study initiation and then annually during a five-year interval. Results: The recurrence rate of polyps increased annually from 5 to 12.5%; the highest rate was noted in the last two years. The five-year cumulative risk of neoplastic lesions was 73% in patients without polypectomy and 20% among those with endoscopic resection (p 0.05). Comparing the recurrence rate of benign lesions (60%) in patients without neoplastic findings with the recurrence rate of adenomas in patients with benign lesions (40%), a higher risk of recurrence was found in the first category, and seemed to be influenced by the personal history of pre-existing adenomatous lesions. CONCLUSION: an increased risk of colorectal polyps recurrence was reported during five year follow up; moreover, during the first three years an increased risk of malignant transformation was observed among cases in which endoscopic resection was not feasible when compared to those in which complete excision was feasible.

Prognostic Significance of Preoperative Inflammation Markers on the Long-Term Outcomes in Peritoneal Carcinomatosis from Ovarian Cancer.

Ovarian cancer remains one of the most lethal gynaecological malignancies affecting women worldwide; therefore, attention has been focused on identifying new prognostic factors which might help the clinician to select cases who could benefit most from surgery versus cases in which neoadjuvant systemic therapy followed by interval debulking surgery should be performed. The aim of the current paper is to identify whether preoperative inflammation could serve as a prognostic factor for advanced-stage ovarian cancer. Material and methods: The data of 57 patients who underwent to surgery for advanced-stage ovarian cancer between 2014 and 2020 at the Cantacuzino Clinical Hospital were retrospectively reviewed. The receiver operating characteristic curve was used to determine the optimal cut-off value of different inflammatory markers for the overall survival analysis. The analysed parameters were the preoperative level of CA125, monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic inflammation index (SII). Results: Baseline CA125 > 780 µ/mL, NLR ≥ 2.7, MLR > 0.25, PLR > 200 and a systemic immune inflammation index (SII, defined as platelet × neutrophil-lymphocyte ratio) ≥ 84,1000 were associated with significantly worse disease-free and overall survival in a univariate analysis. In a multivariate analysis, MLR and SII were significantly associated with higher values of overall survival (p < 0.0001 and p = 0.0124); meanwhile, preoperative values of CA125, PLR and MLR were not associated with the overall survival values (p = 0.5612, p = 0.6137 and p = 0.1982, respectively). In conclusion, patients presenting higher levels of MLR and SII preoperatively are expected to have a poorer outcome even if complete debulking surgery is performed and should be instead considered candidates for neoadjuvant systemic therapy followed by interval surgery.

Bioactive Vitamins and Epigenetic Modifications in Diabetes: A Perspective.

Diabetes is a complex metabolic disease that has been associated with epigenetic changes. External factors such as dietary patterns can induce an imbalance in the pools of micronutrients and macronutrients in the body. Consequently, bioactive vitamins may influence epigenetic mechanisms via several pathways: involvement in the control of gene expression, and in protein synthesis, by acting as coenzymes and co-factors in the metabolism of methyl groups or methylation of DNA and histones. Herein, we present a perspective on the relevance of bioactive vitamins in the epigenetic modifications that occur in diabetes.

Acute myocardial infarction in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) are a heterogeneous group of hematologic malignancies characterized by an abnormal proliferation of cells of the myeloid lineage. Affected individuals are at increased risk for cardiovascular and thrombotic events. Myocardial infarction (MI) may be one of the earliest clinical manifestations of MPNs or may be a thrombotic complication that develops during the natural course of the disease. In the present review, we examine the epidemiology, pathogenesis, clinical presentation, and management of MI in MPNs based on the available literature. Moreover, we review potential biomarkers that could mediate the MI-MPNs crosstalk, from classical biochemical tests, e.g., lactate dehydrogenase, creatine kinase and troponins, to pro-inflammatory cytokines, oxidative stress markers, and clonal hematopoiesis.

Hyponatremia as a Prognostic Factor in Advanced Stage Ovarian Cancer Patients.

Background: hyponatremia represents one of the most commonly encountered conditions in hospitalized patients, multiple mechanisms being cited so far, neoplastic syndromes being an important cause. The aim of the current paper is to analyse the presence and influence of the short- and long-term outcomes of hyponatremia on ovarian cancer patients submitted to surgery for advanced stage ovarian cancer. Method: 57 patients diagnosed with advanced stage ovarian cancer were submitted to surgery between 2014-2020. The patients were further classified according to the preoperative value of sodium into two groups. Results: there were 21 cases with preoperative normal values of sodium and respectively 36 cases with hyponatremia. Patients with preoperative hyponatremia associated a significantly higher rate of early postoperative complications and a significantly poorer long-term outcome. Therefore, cases with hyponatremia reported a mean disease-free survival of 10.8 months and respectively a mean overall survival of 18.5 months while cases with normal natrium levels reported a mean disease-free survival of 31.4 months and respectively a mean overall survival of 49.7 months (p=0.0001 and p 0.001). Conclusions: patients with lower preoperative values of sodium have a higher risk of developing postoperative complications and a significantly poorer outcome when compared to cases presenting normal levels of sodium preoperatively.

Colorectal Cancer: From Risk Factors to Oncogenesis.

Colorectal cancer is the second leading cause of cancer-related mortality worldwide. Numerous pathophysiological mechanisms, such as abnormal cell proliferation, cell differentiation, resistance to apoptosis, invasion of structures adjacent to colorectal tumor cells, and distant metastasis, are involved in colorectal carcinogenesis. These processes are initiated by the complex interaction of a number of genetic and environmental factors, including sedentary lifestyle, obesity, alcohol consumption, smoking, or gut microbiota. Despite the significant progress achieved in the diagnostic and therapeutic management of patients with colorectal cancer, there has been recently a noteworthy increase in the incidence of colorectal cancer in individuals below the age of 50 years. Early-onset colorectal cancer has a different frequency of oncogenic mutations, a higher prevalence of mucinous histology, a distinct deoxyribonucleic acid (DNA) methylation profile, a more distal location, and lower survival rates. A significant improvement in the prognosis of these patients can be achieved through the detection and removal of modifiable risk factors, along with the implementation of personalized screening strategies for individuals at high risk for this malignancy. Furthermore, gaining comprehension of the pathophysiological mechanisms by which these risk factors contribute to the process of oncogenesis may facilitate the discovery of novel therapeutic targets.

Platelet to Lymphocyte Ratio as a Predictive Tool for the Perioperative and Postoperative Outcomes in Advanced Stage Ovarian Cancer.

Background: platelet to lymphocyte ratio remains a significant prognostic factor in different malignancies. The aim of the current paper is to study the correlation between the preoperative values of platelet to lymphocyte ratio (PLR) and the postoperative outcomes in ovarian cancer patients. Method: we conducted a retrospective study on 57 patients submitted to cytoreductive surgery between 2014-2020. We determined the optimal cut off value of PLR for predicting survival outcomes by using the Receiver Operating Characteristic curve a value of 350 being obtained. The patients were further classified in two groups according to the PLR value. Results: there were 37 patients with PLR 350 and respectively 20 patients with PLR 350. Patients in the second group were significantly older and presented significantly higher rates of perioperative complications, a significantly higher level of circulating platelets, of CA125 and respectively a significantly lower level of circulating lymphocytes and of preoperative hemoglobin level. Meanwhile, patients in the second group reported a significantly poorer disease free and overall survival. Conclusions: ovarian cancer patients with higher preoperative levels of PLR trend to have a poorer early and long-term postoperative outcome. Therefore, in such cases more aggressive systemic therapies might be needed.

COVID-19-related Floating Thrombus in the Ascending Aorta - A Case Report.

BACKGROUND/AIM: Multiple aortic mural thrombi at the level of the ascending aorta represent a rare condition, only isolated cases have been reported so far. The aim of the current article was to report the case of a 61-year-old patient diagnosed with this pathology. CASE REPORT: A 61-year-old patient with history of COVID infection six months previously was initially diagnosed with acute upper right limb ischemia and submitted to Fogarty desobstruction. Furthermore, the patient was diagnosed with a free-floating mass in the ascending aorta, for which he was submitted to aortotomy and floating thrombi, measuring 5.6×1.5 cm and 3×1.5 cm, were completely removed. The postoperative outcomes were favorable; at the three month follow up the patient proved to have a perfect circulated aortic lumen and supra-aortic vessels. CONCLUSION: immediate aortic desobstruction followed by reconstruction might be a lifesaving maneuver in ascending aortic thrombosis.

Biliary and Vascular Complications after Liver Transplantation-From Diagnosis to Treatment.

The last decades have brought impressive advances in liver transplantation. As a result, there was a notable rise in the number of liver transplants globally. Advances in surgical techniques, immunosuppressive therapies and radiologically guided treatments have led to an improvement in the prognosis of these patients. However, the risk of complications remains significant, and the management of liver transplant patients requires multidisciplinary teams. The most frequent and severe complications are biliary and vascular complications. Compared to vascular complications, biliary complications have higher incidence rates but a better prognosis. The early diagnosis and selection of the optimal treatment are crucial to avoid the loss of the graft and even the death of the patient. The development of minimally invasive techniques prevents surgical reinterventions with their associated risks. Liver retransplantation remains the last therapeutic solution for graft dysfunction, one of the main problems, in this case, being the low number of donors.

Budd-Chiari syndrome in myeloproliferative neoplasms: A review of literature.

Myeloproliferative neoplasms (MPNs) are defined as clonal disorders of the hematopoietic stem cell in which an exaggerated production of terminally differentiated myeloid cells occurs. Classical, Philadelphia-negative MPNs, i.e., polycythemia vera, essential thrombocythemia and primary myelofibrosis, exhibit a propensity towards the development of thrombotic complications that can occur in unusual sites, e.g., portal, splanchnic or hepatic veins, the placenta or cerebral sinuses. The pathogenesis of thrombotic events in MPNs is complex and requires an intricate mechanism involving endothelial injury, stasis, elevated leukocyte adhesion, integrins, neutrophil extracellular traps, somatic mutations (e.g., the V617F point mutation in the JAK2 gene), microparticles, circulating endothelial cells, and other factors, to name a few. Herein, we review the available data on Budd-Chiari syndrome in Philadelphia-negative MPNs, with a particular focus on its epidemiology, pathogenesis, histopathology, risk factors, classification, clinical presentation, diagnosis, and management.

Clinical and Biological Data in Patients with Pancreatic Cancer vs. Chronic Pancreatitis-A Single Center Comparative Analysis.

INTRODUCTION: In some patients with chronic pancreatitis, the diagnosis of pancreatic cancer can be missed. The objective of the study was to identify clinical and paraclinical data with statistical significance in the differential diagnosis between chronic pancreatitis and pancreatic cancer. MATERIALS AND METHODS: We conducted a retrospective, observational study on a cohort of 120 patients hospitalized over 3 years. The patients were equally distributed in two groups: group A, with 60 patients with pancreatic cancer, and group B, with 60 patients with chronic pancreatitis. The statistical analysis was carried out by using the R program. RESULTS: The comparative analysis of pancreatic cancer vs. chronic pancreatitis revealed a stronger link between pancreatic cancer, female gender (p = 0.001) and age over 60 years (p < 0.001). Patients with pancreatic cancer had higher serum values of aspartate aminotransferase (p 0.005), alanine aminotransferase (p 0.006), total bilirubin (p < 0.001), direct bilirubin (p < 0.001), alkaline phosphatase (p 0.030), C-reactive protein (p = 0.049) and uric acid (p 0.001), while patients with chronic pancreatitis presented slightly higher values of amylase (p 0.020) and lipase (p 0.029). CONCLUSIONS: Female gender, advanced age, elevated aminotransferases, cholestasis markers and uric acid were associated with a higher probability of pancreatic cancer.

Primary Arterial Hypertension and Drug-Induced Hypertension in Philadelphia-Negative Classical Myeloproliferative Neoplasms: A Systematic Review.

The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on cardiovascular risk factors as a singular entity or on organ-specific HTN. Furthermore, available studies reporting findings on drug-induced HTN in MPNs report varying and contradictory findings. In consideration of the above, this study set out to systematically review the available literature and shed light on the occurrence of HTN in MPNs, its association with thrombosis, as well as the drugs used in MPN management that could increase blood pressure. The literature search yielded 598 potentially relevant records of which 315 remained after the duplicates (n = 283) were removed. After we screened the titles and the abstracts of these publications, we removed irrelevant papers (n = 228) and evaluated the full texts of 87 papers. Furthermore, 13 records did not meet the inclusion criteria and were excluded from the systematic review. Finally, a total of 74 manuscripts were entered into the qualitative synthesis and included in the present systematic review. Our systematic review highlights that HTN is the most common comorbidity encountered in MPNs, with an impact on both the occurrence of thrombosis and survival. Moreover, drug-induced HTN remains a challenge in the management of MPNs. Further research should investigate the characteristics of patients with MPNs and HTN, as well as clarify the contribution of HTN to the development of thrombotic complications, survival and management in MPNs. In addition, the relationship between clonal hematopoiesis of indeterminate potential, HTN, cardiovascular disease and MPNs requires examination in upcoming assessments.