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.

Pancreatoduodenectomy En Bloc With Superior Mesenteric Artery Resection for Borderline Resectable Pancreatic Cancer - A Case Report and Literature Review.

BACKGROUND/AIM: Pancreatic head adenocarcinoma represents the most aggressive digestive malignancy, which affects patients worldwide and is associated with poor outcomes especially due to the fact that most cases are diagnosed when local vascular invasion is already present. CASE REPORT: This is a case report of a 44-year-old patient diagnosed with a borderline resectable pancreatic head adenocarcinoma invading the superior mesenteric artery. The patient was submitted to surgery, and intraoperatively the mesenteric artery invasion was found. A pancreatoduodenectomy en bloc with superior mesenteric artery resection was performed while the continuity of the arterial structure was re-established by placing a cadaveric graft. CONCLUSION: In selected cases, extended arterial resections might be needed in order to achieve negative resection margins and therefore, to improve the chances of long-term survival.

Same Clinical Reality of Spontaneous Rupture of the Common Iliac Artery with Pseudoaneurysm Formation-Comparison of Two Therapeutical Solutions, Endovascular Stent-Graft and Open Surgical Correction, for Two Cases and Review of the Literature.

The incidence of isolated iliac artery aneurysms is approximately 2% and common iliac artery pseudoaneurysms are even rarer. A pseudoaneurysm is a localized hemorrhage as opposed to an actual aneurysm, which affects the entire vascular wall. They are typically asymptomatic and only detectable accidentally while looking for other causes. If large and symptomatic, they typically exhibit pressure symptoms as a result of the compression of the structures around them. Common symptoms include generalized stomach pain, urological problems, gastrointestinal bleeding, and neurological symptoms such as leg paralysis or sciatica-like back pain. Rarely, they may exhibit hemodynamic instability together with an aneurysm rupture, which has a high fatality rate. Due to the unique presentation, the diagnosis is typically rarely made and there is little experience with treating it. We report two cases of common iliac artery pseudoaneurysm found in two patients who had no notable medical history and who we chose to repair through the endovascular technique in the first case, an approach that has gained more ground for vascular repair worldwide, making it the current go-to method, and for the second case we chose a more traditional approach, through open surgery.

Intrahepatic Cholangiocarcinoma - Where Do We Stand Today? Literature Review.

Intrahepatic cholangiocarcinomas represent rare and aggressive malignancies developing from the second order bile ducts to the smaller biliary branches. The aim of this narrative review is to discuss about the main diagnostic and therapeutic challenges in order to help medical and surgical oncologists to gain familiarity in regard to this subject. Articles discussing about epidemiology, histology, diagnostic, perioperative management and surgery which were published from January 2000 to September 2023 included in Cochrane Library, PubMed, Embase, MedLine, Web of Science, Elsevier, Google Scholar databases were reviewed. Articles reviewed in the current paper came to demonstrate that the main problem in such cases is related to the fact that most cases remain asymptomatic for a long period of time and therefore are diagnosed in advanced stages of the disease when curative procedures are feasible after performing extended visceral sacrifice or even worse, are no longer possible; however, the most efficient therapeutic strategy in order to improve the long term outcomes remains radical surgery. In this respect, attention was focused on improving the accuracy of the diagnostic tools and on identifying non-surgical therapeutic options which might increase the chances of achieving complete resection. Intrahepatic cholangiocarcinoma represent rare aggressive tumors with poor outcomes especially if radical surgery is not feasible.

Pulmonary Crohn's Disease or Crohn's Disease with Lung Sarcoidosis? A Case Report and Literature Review.

BACKGROUND: Crohn's disease and ulcerative hemorrhagic colitis are forms of granulomatous inflammatory intestinal disease, which usually affects the gastrointestinal tract. There are also reported rare localizations at the skin, kidney, joints, liver and eye level. Pulmonary involvement is relatively rare, and it is most commonly reported in suppuration with bronchiectasis. On the other hand, sarcoidosis is, in principle, a thoracic localization of a granulomatosis disease, although bowel, skin and intestinal disorders are described. There is not a clear line to separate Crohn's disease from sarcoidosis with, possibly because they are, in fact, considered to have the same inflammatory granulomatosis disease pathology. The diagnoses of the two entities, sarcoidosis and Crohn's disease, are based on non-pathognomonic, inclusive clinical and paraclinical criteria, without elements of the mutual exclusion of typical locations. CASE REPORT: We present a very rare case of a young male, already diagnosed with small-bowel Crohn's disease. Granulomatous lung disease with major hemoptysis requires emergency surgery. An intraoperative assessment revealed a necrotic hemorrhagic lesion located in the left lower lobe and a lobectomy was performed. The final pathological report showed the presence of non-caseous granulomatous inflammation, with the identification of specific multinucleated giant cells. CONCLUSIONS: The identical diagnostic principles of Crohn's disease and sarcoidosis, Crohn's disease as a predecessor to pulmonary lesions, the clinical picture and the necrotico-hemorrhagic appearance of the unilateral pulmonary lesion, which are similar to aggressive necrotico-hemorrhagic or perforating intestinal forms, are arguments in favor of the diagnosis of pulmonary Crohn's disease and not pulmonary sarcoidosis. At the same time, in general, the two diseases have overlapping elements, suggesting they are, in fact, not the same disease with different facets.

Diastolic versus Systolic Left Ventricular Dysfunction as Independent Predictors for Unfavorable Postoperative Evolution in Patients with Aortic Regurgitation Undergoing Aortic Valve Replacement.

Background and Objectives: Chronic severe aortic valve disease is associated with important changes in left ventricle (LV) performance associated with eccentric or concentric LV hypertrophy. We aimed to assess the immediate prognostic implications of the type of the LV diastolic filling pattern (LVDFP) compared with LV systolic performance in patients with severe aortic regurgitation (AR) undergoing aortic valve replacement (AVR) and to define the independent echographic predictors for the immediate and long-term prognoses. Materials and Methods: We performed a prospective study enrolling 332 AR patients undergoing AVR, divided into two groups: Group A­201 pts with normal LV systolic function, divided into two subgroups (A1: 129 pts with a nonrestrictive LVDFP and A2: 72 pts with restrictive LVDFP), and Group B­131 pts with LV systolic dysfunction (LV ejection fraction LVEF < 50%), divided into two subgroups (B1: 83 pts with a nonrestrictive LVDFP and B2: 48 pts with restrictive LVDFP). Results: The early postoperative mortality rate was higher in patients with a restrictive LVDFP (11.12% in A2 and 12.5% in B2) compared with normal LV filling (2.32% in A1 and 7.63% in B1, p < 0.0001), regardless of the LVEF. The restrictive LVDFP­defined by at least one of the following echographic parameters: an E/A > 2 with an E wave deceleration time (EDt) < 100 ms; an isovolumetric relaxation time (IVRT) < 60 ms; or an S/D ratio < 1 in the pulmonary vein flow­was an independent predictor for early postoperative mortality, increasing the relative risk by 8.2-fold. Other independent factors associated with early poor prognosis were an LV end-systolic diameter (LVESD) > 58 mm, an age > 75 years, and the presence of comorbidities (chronic obstructive pulmonary disease-COPD or diabetes mellitus). On a medium-term, an unfavorable evolution was associated with: an age > 75 years (RR = 8.1), an LV end-systolic volume (LVESV) > 95 cm3 (RR = 6.7), a restrictive LVDFP (RR = 9.8, p < 0.0002), and pulmonary hypertension (RR = 8.2). Conclusions: The presence of a restrictive LVDFP in patients with AR undergoing AVR is associated with both increased early and medium-term mortality rates. The LV diastolic function is a more reliable parameter for prognosis than LV systolic performance (RR 9.2 versus 2.1). Other independent predictors for increased early postoperative mortality rate were: an age > 75 years, an LVESD > 58 mm, and comorbidities (diabetes mellitus, COPD), and for unfavorable evolution at 2 years postoperatively: an age > 75 years, an LVESV > 95 cm3, and severe pulmonary hypertension.

Impact of retroperitoneal tumors on the digestive tract (Review).

Primary retroperitoneal tumors are a rare group of neoplasms that often prove to be a real therapeutic challenge. The clinical picture is in most cases nonspecific, being the result of nearby tissue and organ compression, displacement and/or invasion, and it usually includes a variety of deceiving signs and symptoms that may lead to diagnostic errors. During the course of the disease, up to half of the patients diagnosed with retroperitoneal tumors can develop gastrointestinal symptoms, the incidence of such symptoms significantly increasing with tumor size. Therefore, symptoms such as abdominal distension, diffuse abdominal pain or epigastric pain mimicking acute pancreatitis, diarrhea, constipation, jaundice, hematemesis, melena and hematochezia can be found. The mainstream treatment for primary retroperitoneal tumors is surgical excision, chemotherapy and radiotherapy but associated with poor results. Due to their rarity, as well as to the complexity of these tumors, patients should be managed in high volume centers that allow the possibility of a multidisciplinary approach.

Implications of Type 2 Diabetes Mellitus in Patients with Acute Cholangitis: A Systematic Review of Current Literature.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) has been associated with higher rates and poorer prognosis of infections, mainly due to poor glycemic control, reduced response of T-cells and neutrophils, and impaired migration, phagocytosis, and chemotaxis of leukocytes. However, the impact of T2DM on acute cholangitis (AC) has not been assessed so far. Thus, we aimed to explore this association by means of a systematic review of the literature. METHODS: This systematic review was carried out based on the recommendations stated in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed/MEDLINE, Web of Science and SCOPUS databases to identify relevant publications depicting an association between T2DM and AC from the inception of these search services up to present. RESULTS: We detected a total of 435 eligible records. After we applied the inclusion and exclusion criteria, a total of 14 articles were included in the present systematic review. Included manuscripts focused on the potential role of T2DM as a risk factor for the development of AC and on its contribution to a worse prognosis in AC, e.g., development of sepsis or other complications, the risk of AC recurrence and the impact on mortality. CONCLUSIONS: As compared to non-diabetic individuals, patients with T2DM have a higher risk of AC as a complication of choledocholithiasis or gallstone pancreatitis. Several oral hypoglycemic drugs used in the management of T2DM may also be involved in the onset of AC. Diabetic patients who suffer from AC have a higher likelihood of longer hospital stays and sepsis, as well as a higher risk of mortality and more severe forms of AC as compared to non-diabetic individuals.