Search

In Romania, cervical cancer is the second most frequent neoplasm among women of 15 to 44 years of age, mainly due to a lack of prevention efforts. The purpose of this study is to assess the current knowledge and attitude towards HPV infection and immunization among medical students. Such information is vital in order to properly assess the current shortcomings of our medical system in the struggle of lowering cancer incidence. A cross-sectional questionnaire-based study was carried out in 2016 and in 2018 on a total of 1,133 participants (median age of 21.9 years, 572 students in 2016 and 562 in 2018). No statistical differences between males and females regarding knowledge of HPV vaccine were found (chi-square 0.046, df = 1, p = 0.83). Moreover, between the 2016 and the 2018 groups, no noticeable changes in HPV awareness and information were observed (2016: chi-square: 0.003, df = 1, p = 0.955; and 2018: chi-square: 0.061, df = 1, p = 0.805). Even though the participants have noted reliable media and medical staff as their main sources of information, our study revealed poor general knowledge, no improvement in perception, and a lack of prophylactic action.

Liana Suciu,1 Maria Suciu,1 Mirela Voicu,1 Raluca Mureșan,2 Florina Viorica Pârv,3 Valentina Buda,1 Carmen Cristescu1 1Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy Victor Babeș, Timisoara, Romania; 2Department of Mathematics, Faculty of Mathematics and Informatics, West University, Timisoara, Romania; 3Department of Cardiology, Faculty of Medicine, University of Medicine and Pharmacy Victor Babeș, Timișoara, RomaniaCorrespondence: Maria Suciu; Mirela VoicuDepartment of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, University of Medicine and Pharmacy Victor Babeș, Eftimie Murgu Square, No. 1-3, Timișoara, RomâniaTel +40723319050; +40745763424Email suciu.maria@umft.ro; mavoicu@yahoo.comPurpose: Romania has a high prevalence of hypertension (45.1% in 2016). Whether this is attributable to a low rate of treatment adherence—which can aggravate the pathology and reduce patients’ quality of life (QoL)—is unknown. To address this point, the present study investigated the factors that influence short- and long-term adherence and QoL in patients with arterial hypertension using a specially designed questionnaire.Patients and Methods: The study enrolled 289 patients at different stages of hypertension with or without comorbidities. The diagnosis of hypertension was established by the cardiologist, and treatment regimens were communicated by patients to the clinical pharmacist who administered the questionnaire, which comprised 7 domains with variable numbers of items.Results: The majority of surveyed patients (57.43%) considered that their capacity for effort was decreased because of their hypertension, with 65.05% reporting that they were affected by symptoms associated with high blood pressure (eg, headache and dizziness). Most patients (71.28%) understood the consequences of discontinuing their medication and the severe complications of hypertension, and 69.55% indicated that they would not stop treatment if they experienced side effects. For 53.28% of patients, social activity was significantly affected by their condition. Only 47.05% of patients underwent regular mandatory medical examinations and 55.36% periodically monitored their blood pressure at home. A regression analysis revealed correlations between specific questionnaire items and patient characteristics.Conclusion: Nonpharmacologic factors that were shown to influence patients’ adherence to treatment and QoL included the level of health education and knowledge of disease complications, self-monitoring of hypertension, and consultation with medical and pharmaceutical healthcare providers regarding hypertension and its treatment.Keywords: arterial hypertension, quality of life, adherence, medication

The prevalence of Parkinson’s disease (PD), the second most common neurodegenerative disorder, has dramatically increased worldwide from 2,5 million in 1990, to 6,1 million in 2016. This condition continues to unfold its complexity, being nowadays recognized more as a syndrome rather than a disease. Beside the motor symptoms, the non-motor features, which can appear as early as twenty years before the classic onset, are now included in the diagnostic criteria. Increased public awareness, early recognition, and intervention (mostly neuroprotective) could highly increase the quality of life of people suffering from PD. We believe that these measures must be taken without delay, in order to counteract the increasing prevalence of PD worldwide. Abbreviations: PD = Parkinson’s disease, GBD = Global Burden of Diseases, HY = Hoehn-Yahr scale, SD = standard deviation

Retinopathy is one of the most severe diabetes-related complications, and macular edema is the major cause of central vision loss in patients with diabetes mellitus. Significant progress has been made in recent years in optical coherence tomography and angiography technology. At the same time, various parameters have been attributed the role of biomarkers creating the frame for new monitoring and treatment strategies and offering new insights into the pathogenesis of diabetic retinopathy and diabetic macular edema. In this review, we gathered the results of studies that investigated various specific OCT (angiography) parameters in diabetic macular edema, such as central subfoveal thickness (CST), cube average thickness (CAT), cube volume (CV), choroidal thickness (CT), retinal nerve fiber layer (RNFL), retinal thickness at the fovea (RTF), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), choroidal vascularity index (CVI), total macular volume (TMV), central choroid thickness (CCT), photoreceptor outer segment (PROS), perfused capillary density (PCD), foveal avascular zone (FAZ), subfoveal neuroretinal detachment (SND), hyperreflective foci (HF), disorganization of the inner retinal layers (DRIL), ellipsoid zone (EZ), inner segment/outer segment (IS/OS) junctions, vascular density (VD), deep capillary plexus (DCP), and superficial capillary plexus (SCP), in order to provide a synthesis of biomarkers that are currently used for the early diagnosis, assessment, monitoring, and outlining of prognosis.

Background and aims. Our aim is to examine the relationship between the level of education, background, tumor size and lymph node status on the treatment outcome in a group of patients with early and locally advanced breast cancer (BC) by using the restricted mean survival time (RMST), which summarizes treatment effects in terms of event-free time over a fixed period of time. Methods. We evaluated the prognostic values in 143 patients treated for early BC at Elias University Emergency Hospital, Bucharest, Romania and followed up for a maximum of 36 months. The protocol was amended to include the levels of education (gymnasium, high school, or university), the background (urban or rural) and the clinical stage (primary tumor (T) and regional nodes (N)). The methodology consisted in using a Kaplan–Meier analysis and RMST for the entire sample and Cox regression, for the variables with statistical influence. The principal endpoints of the study were overall survival (OS) and progression free survival (PFS). Results. The level of education had impact both on RMST OS (35.30 vs. 26.70) and death HR (hazard ratio) in the group of patients with general school level, compared with those with graduated university. In this study, the urban or rural background did not impact the outcome, probably because in this study we included predominantly patients from urban areas (83%). Although clinical tumor size measurements did not impact the outcome, the clinical staged lymph node influenced both OS (p=0.0500) and PFS (p=0.0006) for the patients with palpable or imaging proof of lymph node involvement of station 2 or 3. Conclusions. RMST provides an intuitive and explicit way to express the effect of those risk factors on OS and PFS in a cohort of early breast cancer patients. Low level of education and high-grade clinical lymph node status negatively influences the outcome of this cohort of BC patients.

Background, objectives: Histological diagnosis of control biopsies in patients with heart transplant represents a significant step of monitoring, with a great influence on adjusting immunosuppressive treatment. Histological lesions are usually related to ischemia and reperfusion, with varying degrees of intensity. This study aimed to highlight the most important aspects of the histological diagnosis and differential diagnosis of postoperative myocardial lesions associated or unrelated to rejection in heart transplant. Materials and Methods: This retrospective study involved 53 patients who received cardiac transplant between 2000 and 2017. Patients were monitored by lesion quantification of endomyocardial biopsies, with diagnoses established based on biopsy material in the early, medium and late post-transplant periods. Hematoxylin eosin, Masson’s trichrome, and Van Gieson stains were used; immunohistochemical determinations used CD4, CD20, CD45, CD68, HLA-DR, VEGF and CD31. Results: Ischemia and reperfusion lesions were diagnosed on all biopsies in the first 6 weeks post-transplant. Nine cases of the Quilty effect were identified, and in 12 cases, the biopsies were performed on the same spot as previous biopsies. A significant number of transplanted patients presented cytomegalovirus that was difficult to diagnose on endomyocardial biopsies. Conclusions: The detailed study of ischemia and reperfusion lesions, as well as of changes un-related to rejection becomes a major objective in the short, medium and late post-transplant period. Overdiagnosis of rejection induces changes of the immunosuppressive therapeutic protocol, with alarming repercussions on cytomegalovirus reactivation, and risks of potentiating inflammation, myocyte destruction and the recurrence of disorders related to both inducing and aggravating heart failure.

Objective The presence of extrathyroidal extension (ETE) is generally considered as an indication for total thyroidectomy for differentiated thyroid cancer. The accuracy of neck ultrasound for the diagnosis of ETE is controversial. The aim of this study was to assess the diagnostic accuracy of preoperative ultrasound evaluation of ETE. Methods The retrospective and observational study of consecutive patients operated between 2016 and 2019 for cytologically suspicious or indeterminate thyroid nodules were analyzed. US images obtained preoperatively were retrospectively reviewed to identify signs of minimal or gross ETE. Histology was considered as the golden standard for diagnosis of ETE. The sensitivity, specificity, positive (PPV) and negative predictive values (NPV), and accuracy of US were evaluated. Results A cohort of 305 patients (75% females, median age 48 years) with 378 nodules (median size 18 mm) was studied. Seventy-five percent of the nodules (n = 228) were malignant on histology and ETE was present in 106 cases (28%): 83 minimal ETE and 23 gross ETE. Suspicion of minimal ETE on preoperative ultrasound was found in 50 (13%) with a sensitivity of 30%, a specificity of 93%, a PPV of 62% and an NPV of 78%, with an accuracy of 76%. Gross ETE on ultrasound was found in 19 (5%) nodules with a sensitivity of 78%, a specificity of 99.7% a PPV of 94.7% an NPV of 98.6% and an accuracy of 98%. Conclusions Preoperative US is very specific and accurate in diagnosing gross ETE which impacts the extent of initial surgery for thyroid cancers.

Bicuspid aortic valve (BAV) is the most common heart valve malformation, and it may be associated with the development of long-term complications, such as aortic stenosis (AS) secondary to valvular calcification and aortic insufficiency (AI), with or without ascending aortic aneurysm (AAA). This study was performed at the Institute of Cardiovascular Diseases, Timişoara, Romania, from 2015 through 2018 and included a total of 105 patients with BAV. Out of the 105 BAV patients, 14 displayed AAA, alongside either AS or AI, and were selected undergo aortic valve replacement (AVR) alongside surgical replacement or aortoplasty of the ascending aorta, and the elastic fiber loss in the ascending aortic wall was evaluated for each patient. Two surgical interventions used alongside AVR in BAV patients with AAA and AS or AI were compared in this study: reduction ascending aortoplasty (RAA) and ascending aorta replacement (AAR). Postoperative follow-ups have shown RAA is useful short-term but that, in contrast to AAR, it leads to aortic redilatation over time. These results can contribute to a major future meta-analysis with the goal of improving the current clinical practice guidelines for BAV aortopathy.

Introduction. Stroke is the second cause of mortality worldwide, after the ischemic coronary disease, and the first cause of long term-disability. Recent studies report that ischemic stroke (IS) in young patients is increasing in incidence, even though the overall stroke hospitalization rate is decreasing. Stroke in the young, working individuals significantly affects the quality of life (QoL) and also determines an important, negative economic impact by reducing the workforce. Material and method. The aim of this paper is to present the results of a 4-year observational, retrospective study on all patients between 18-49 years, who suffered from acute IS and were admitted and investigated in the Neurology Clinic of Sibiu and the CVASIC Research Center. Clinical evaluations, imaging investigations, and risk factor evaluations were performed on all patients in order to elucidate the etiology and organize according to the TOAST classification. Results and discussions. 114 patients with ischemic stroke were included in the study. 76% of the subjects fall into the 40-49 age class. In respect to the TOAST classification, most cases of IS were of UE (rural

Tuberculosis (TB) in pregnancy is not only a matter of the past; it is also a current problem. These days, TB appears through mass migration and tourism in countries where it was believed that this condition is eradicated. Adequate knowledge about the medical history of patients, risk factors, diagnosis and treatment of tuberculosis should be part of the armamentarium of each physician involved in clinical practice. TB is mainly found in urban and socially deprived areas. Due to the length of the treatment, there is an increased risk of drug resistance in partially treated patients. Strong knowledge about the history, risk factors, diagnosis and treatment of TB should be part of the armamentarium of each physician. Many practitioners are reluctant to request a chest X-ray in pregnancy due to the fear of harming the fetus. Bypassing a diagnosis can have a devastating effect on the mother and fetus, as well as their family and medical staff. This article discusses the matters of diagnosis and treatment of asymptomatic infection and active TB in pregnancy.

In this paper we present the clinical course during 3 years of follow-up of a patient who was admitted in our clinic being formerly diagnosed with sporadic amyotrophic lateral sclerosis (ALS). After he was diagnosed in 2016 with ALS, he was treated with Riluzole for 6 months, but his symptoms aggravated in this period of time. During the first admission in our department, he presented a flail-arm syndrome with bilateral scapula alata, facio-scapulo-humeral wasting, fasciculations, abolished reflexes in the upper limbs, generalized pruritus, xeroderma and weight loss over 25 kg. Extensive investigations revealed the HIV infection for which he was referred then to the nearest infectious diseases center for proper treatment. A follow-up spanning on 3 years, revealed increased muscle power and improved muscle bulk after HAART therapy. In this paper we present the case report and a short to the point literature review of amyotrophic lateral sclerosis mimics in HIV infection.

Our study aimed to assess the longitudinal change of cognitive functions in depressed patients after a 6-month interval free of mood symptoms.In a longitudinal study, 65 patients diagnosed with recurrent major depressive disorder were evaluated twice with neurocognitive tests, during an acute depressed episode and after 6 months of euthymia. The cognitive dimension was assessed with neuropsychological tests of attention and processing speed, memory, verbal fluency, psychomotor speed and executive functions. The severity of depression was evaluated through Hamilton Depression Rating Scale - 17 items. All the results were compared with the outcomes of 35 healthy controls, both in depression and euthymia.Depressed patients compared to controls displayed significant statistical differences for most cognitive tests applied, verbal and working memory being the most severely impaired. They were still impaired at the second evaluation. Significant differences were noted between the euthymic and control group, too. Between the depression phase and euthymia, patients obtained significant improvement for attention and processing speed, verbal fluency, motor speed and executive functions.Results from the current study indicate that cognitive impairment is more severe for depressed patients, decreases for euthymic subjects, and lasts longer after depressive symptoms remit.

BACKGROUND Malnutrition is frequently encountered in patients with cirrhosis and appears to significantly impact their prognosis. While evaluating the burden of malnutrition in cirrhosis is gathering momentum, as suggested by multiple recently published reports, there is still a persistent scarcity of solid data in the field, especially with regards to the role of nutritional interventions. AIM To assess the prevalence of malnutrition in patients with advanced cirrhosis and to evaluate its impact on survival. METHODS One hundred and one consecutive patients with advanced cirrhosis were screened for malnutrition using the Subjective Global Assessment (SGA) criteria and the mid-arm circumference (MAC). Malnutrition was defined as SGA class B and C and MAC < 10th percentile. All patients were interviewed regarding their food intake using an adapted questionnaire. Subsequently, total energy intake was calculated and further subdivided in main nutrients. The data were then compared to the available recommendations at the time of analysis to assess adherence. RESULTS 54/79 patients (68.4%) in the decompensated group had malnutrition, while only 3/22 patients (13.6%) were malnourished in the compensated group. After a median follow-up time of 27 mo (0-53), the overall mortality was 70%. Survival was significantly lower among patients with malnutrition. The mortality rates were 50% at 1 year and 63% at 2 years for the patients with malnutrition, compared to 21% at 1 year and 30% at 2 years for patients without malnutrition (P = 0.01). On multivariate analysis, the factors independently associated with mortality were age, creatinine level and adherence to the protein intake recommendations. The mortality was lower in patients with the appropriate protein intake: 8% at 1 year and 28% at 2 years in the adherent group, compared to 47% at 1 year and 56% at 2 years in the non-adherent group. CONCLUSION The prevalence of malnutrition is high among patients with advanced cirrhosis and might be related in part to a low adherence to nutritional recommendations, especially with regards to protein intake.

Hepatocellular carcinoma is one of the most common liver tumours. At the time of diagnosis, only 20% of patients are suitable for liver resection for curative purposes. In patients who are not suitable for surgical resection, chemoembolization of the hepatic artery is a viable therapeutic option. We present the case of a 60-year-old male patient being admitted with a diagnosis of liver tumour in the right liver lobe. Abdominal angio-CT examination revealed the existence of a tumour formation of 9x10 cm in the liver segments IV, VIII. Given the large size of the tumour, as well as the patient’s comorbidities, it was decided to practice hepatic chemoembolization with Irinotecan. The clinical evolution was favourable, the patient being discharged 48 hours after the intervention. Hepatic transarterial chemoembolization is a viable alternative in the treatment of patients with unresectable hepatocellular carcinomas, which may improve the prognosis of these patients.

Introduction Recent changes in the adjuvant treatment of melanoma have raised interest in confirming relapse-free survival (RFS) as a surrogate for overall survival (OS). Methods We explore this issue with the meta-analytic framework, using individual patient data from the European Organisation for Research and Treatment of Cancer (EORTC) 18071 trial of ipilimumab and published results from other adjuvant trials. Results The individual patient data analysis results at a median follow-up of 5.3 years showed a strong association between RFS and OS at the patient level (ρ = 0.84; 95% confidence interval [CI]: 0.82–0.87) and a moderate association at the trial level (R2 = 0.59; 95% CI: 0.08–1.00). Conclusions The trial-level association previously observed in interferon-based trials appeared to be maintained when the EORTC 18071 results were added to a regression analysis using published results from other trials. More data from adjuvant trials are required to confirm the strength of association between RFS and OS in this setting.

The aim of the article was to determine the association between neutrophil to lymphocyte-ratio (NLR), clinical disease severity and joint effusion in patients with early knee osteoarthritis. We evaluated 79 patients with mild knee degeneration. We obtained NLR from routine hematology panels. As controls, 1260 hematology panels were also obtained. Clinical severity was evaluated from patient reported outcome scores: International Knee Documentation Committee Subjective Knee Evaluation Form, Knee Disability And Osteoarthritis Outcome Score For Joint Replacement, Tegner-Lysholm scale and Euroqol EQ-5D-5L questionnaire. Joint effusion was determined by ultrasound. For the statistics software R, version 3.4.4 was used. There were differences in demographics but not in NLR between the study patients and controls (2.03 versus 1.98, p=0.606). There was no correlation between NLR and joint effusion (r2= - 0.121) or between NLR, joint effusion and any other parameter recorded (r2 from - 0.134 to 0.190). In the multiple regression model, NLR was minimally influenced by age (p=0.059) and KOOSJR (p=0.023). Neutrophil to lymphocyte ratio is within normal limits in patients with early stage knee osteoarthritis and is not associated with clinical severity or with joint effusion.

Background. Increased arterial stiffness assessed by pulse wave velocity (PWV) measurement is a marker of arterial wall dysfunction and has an independent predictive value for adverse cardiovascular outcomes. A positive correlation between the neutrophil-to-lymphocyte ratio (NLR) and PWV has been reported in chronic inflammatory conditions and the general population as well. Furthermore, an association between NLR and PWV has been assumed in hypertensive patients. However, the available data are scarce. The objective of the study was to validate the association between NLR and PWV in a homogenous group of controlled-hypertensive patients without chronic inflammatory conditions. Material and methods. A retrospective observational study was conducted in outpatient cardiology and a general practice. A total number of 25 already on-target treated essential hypertensive, non-diabetic and non-chronic kidney disease (non-CKD) patients were selected. PWV was automatically calculated for each patient using the ABPM BPLab® device. The following laboratory data were collected: complete blood count, fibrinogen, alkaline phosphatase, lactate dehydrogenase, uric acid, serum glucose, total cholesterol, triglycerides, iron, calcium, and creatinine. Neutrophil-to-lymphocyte ratio was calculated. Antihypertensive treatment classes were also assessed. Results. A correlation between increased NLR and PWV in a homogenous group of controlled-hypertensive patients was identified. Conclusions. There is an evident relation between increased NLR and increased PWV in controlled hypertensive patients without evidence of chronic inflammatory conditions.

Introduction. Infections in newborns are a widely studied topic worldwide. Neonatal infections are of two types: those with early onset, acquired from microorganisms from the female genital tract or peripartum and those with late onset, which appeared as a result of invasive procedures, due to nosocomial or invasive germs peri- or postpartum. Objectives. The aim of the study was to identify predictors of early-onset neonatal infections. Material and methods. We conducted a prospective study at the Neonatology Clinic within the County Clinical Hospital in Tg. Mures, Romania, between January 2017 and March 2019. Results. The study included 120 newborns, of which 15 (12.5%) had an APGAR score of 10 per 1 minute. At 5 minutes, 57 (47.5%) had an APGAR score of 10. Type of birth: 59 (49.2%) of the patients were born vaginally and 61 (50.8%) by cesarean section. The average of the gestational age was 39.04 weeks. The average weight at birth was 3,197.33 g, and at discharge was 3,126.12 g. The average length of the new-borns was 51.62 cm, and the average of the cranial perimeter was 33.48 cm. Most frequently, patients presented infectious pathologies, early neonatal (n = 40), frequently associated with the damage of the lung system. The average length of time spent in hospital was of 4 days, with an average of 6.15 days. The APGAR score at 1 minute and 5 minutes was statistically significantly correlated with the number of days of hospitalization and parity of the mother. Conclusions. The APGAR score at 1 minute and 5 minutes was the most accurate indicator for the risk of neonatal infection in our study. Its values correlated with the number of days of hospitalization. The number of hospitalization days was also correlated with parity.

Introduction: The purpose of the paper was to evaluate the indications, fitting, advantages and functional results of Kerasoft 3 contact lenses in keratoconus. Material and method: A retrospective single center study was performed at Oculens Private Clinic in Cluj-Napoca, Romania. Our study included 61 eyes of 35 patients diagnosed with keratoconus in different stages of evolution fitted with Kerasoft 3 lens. The study was undergone between August 2015 and January 2019. Results: In our study, the mean age of the patients was 26.36±8.69 years. The group of study included 80.32% males and 19.62% females. Regarding previous surgeries, CXL was performed in 25 eyes, ICR in 1 eye, CXL and ICR in 15 eyes. The mean BCVA habitual was 0.38±0.19 logMar and with the lens 0.22±0.23 logMar (p

Objective: Congenital heart disease (CHD) is the most common birth defect and represents the leading cause for mortality and morbidity in infants and young adults. Early fetal echocardiography is usually considered a highly specialized scan. The goal of this study is to evaluate the impact of operator's experience in assessing still images of the 4-chamber view and 3-vessels view and to evaluate the feasibility and the performance of a first trimester screening protocol for CHD.Methods: An online questionnaire consisting of still images of the 4-camber view and 3-vessel view from 50 normal and abnormal cases was reviewed by an expert group made of seven obstetricians specialized in fetal medicine and a nonexpert group made of 13 obstetricians that are certified in ultrasound. After individually visualizing each image set made of the 4-chamber view and 3-vessel view, they had to conclude if the case was normal or abnormal and what images were abnormal.Results: A total of 50 image sets of both normal and abnormal fetal hearts were examined by the 20 reviewers, resulting in 1000 evaluations. The expert group achieved a detection rate of 97.1% with a false positive rate of 5.7%. The nonexpert group achieved also a good detection rate of 91.3% but with a much higher false positive rate of 33.9%. The most frequently missed CHD involved the great arteries and had a normal 4-chamber view. In the majority of false positive cases the 3-vessel view was incorrectly interpreted as abnormal.Conclusions: A screening protocol for CHD, based on the 4-chamber view and 3-vessel view alone can offer a good detection rate for CHD with a small false positive rate, but only if it is implemented by highly specialized sonographers.

Atherosclerotic plaque ruptures with subsequent intraluminal thrombosis are the most prevalent causes of acute coronary syndromes, ischemic stroke, acute limb ischemia or cardiovascular death. Hyperlipidemia is no longer considered the primary cause of atherosclerotic disease, as recent data supports the involvement of other triggers such as age, excessive activation of sympathetic nervous system in arterial hypertension, and most importantly, inflammation. Arteriosclerosis is a consequence of interaction between similar mechanisms resulting in arterial stiffening. Furthermore, wall stiffening resulted from the arteriosclerotic process is a risk factor for atherosclerotic disease. This unstructured literature review aimed to present the underlying remodelling processes and mechanisms for atherosclerosis and arteriosclerosis highlighting the common aspects of this two entities and the continuous interrelation that eventually leads to cardiovascular events.

PURPOSE Three new therapies have been approved recently for the adjuvant treatment of stage III melanoma, substantially reducing the risk of tumor recurrences. This study evaluates 3 independent data sets to clarify the survival probabilities of patients with stage III melanoma. PATIENTS AND METHODS The Central Malignant Melanoma Registry (CMMR) evaluated 1,553 patients with a primary diagnosis of stage III melanoma from 2000 to 2012. Studies from the European Organisation for Research and Treatment of Cancer (EORTC), of 573 patients in the observation arm of the 18991 study and 445 patients in the placebo arm of the 18071 study, were evaluated as reference cohorts. The survival outcomes were compared with the published American Joint Committee on Cancer version 8 (AJCCv8) stage III survival data. RESULTS For the CMMR stage III cohort versus the AJCCv8 cohort, the melanoma-specific survival (MSS) rates at 5 years were 67% versus 77%, and at 10 years were 56% versus 69%, respectively. For stage IIIA, the MSS rates at 5 years were 80% versus 93%, and at 10 years were 71% versus 88%; for stage IIIB, the MSS rates at 5 years were 75% versus 83%, and at 10 years were 61% versus 77%. The MSS rates of the EORTC studies either overlapped with or were lower than, the CMMR data. CONCLUSION The MSS rates in the CMMR and EORTC cohorts over the entire stage III are less favorable than those published in AJCCv8. This is particularly true for substages IIIA and IIIB.

Dilated cardiomyopathy (DCM) is the most common type of cardiomyopathy in children. Heart transplantation is considered standard therapy in dilated cardiomyopathy with end-stage heart failure. We present a case of a 15-year-old patient diagnosed with DCM in the neonatal period, who underwent heart transplantation for end-stage heart failure. Despite the use of induction therapy, the endomyocardial biopsy performed at two weeks post-transplant revealed mixed moderate cellular (2R) and humoral (pAMR2) allograft rejection. Aggressive rejection treatment was initiated with good outcome. Besides endomyocardial biopsy, advanced echocardiography can also be a valuable noninvasive tool for rejection assessment.

Introduction Relapsing polychondritis (RP) is a rare disease evolving with recurrent cartilage inflammation, but also with ocular, respiratory, cardiac and vascular involvement. Associations with various autoimmune disorders and with hematological diseases, mainly leukemia, lymphoma and myelodysplastic syndrome and rarely with hemolytic anemia, have been described. We report a 63-year patient with thyroiditis and pernicious anemia in whom a left eye necrotizing scleritis led to the diagnosis of RP and common variable immune deficiency (CVID). The necrotizing scleritis was successfully operated with scleral graft. However, the disease control was difficult to be achieved with glucocorticoids and various immune suppression regimens tried (including cyclophosphamide, cyclosporine, azathioprine, leflunomide and infliximab) along with immunoglobulin substitution. The association of RP and CVID or CVID-like diseases is rare, another 4 cases having been reported. We review the literature and discuss the diagnostic and management difficulties. A multidisciplinary team approach is necessary in this setting.

Introduction: Our study investigated the importance of inflammation markers – ratio of platelets and lymphocytes (PLR), ratio of neutrophils and lymphocytes (NLR) and ratio of lymphocytes and monocytes (LMR) – as predictive markers in the occurrence of fistula or stenosis in patients diagnosed with gastric adenocarcinoma who underwent gastric resections. Materials and Methods: We conducted a retrospective study of 178 patients diagnosed with gastric adenocarcinoma. The included patients were divided into 3 groups: group 1 (77 patients, who underwent lower gastrectomy), group 2 (27 patients, who had upper polar gastrectomy otherwise known as proximal gastrectomy), group 3 (74 patients, who underwent total gastrectomy). Ratios of PLR, NLR, respectively LMR were calculated for all patients. Results: Out of 178 patients 52 (29.2%) developed postoperative stenosis and 16 patients (9.0%) had postoperative fistulae. The occurrence of anastomotic stenosis was associated with significantly higher preoperative platelet counts (p=0.043) and PLR values (p=0.023). ROC curve analysis indicated that the optimal PLR value for the prediction of gastric stenosis was 198.4 (AUC= 0.609, sensitivity: 59.6%, specificity: 61.9%). For the prediction of fistulization PRL also displayed the highest performance among the analyzed hematological parameters (AUC=0.561, sensitivity: 43.7%, specificity: 81.5%, cut-off value 116.6. Conclusion: Our study indicates the importance of PLR as e predictive factor in the occurrence of anastomotic complications (fistulae or stenosis) immediately following surgery in patients with gastric adenocarcinoma that undergo gastric resections. Further prospective studies on larger groups of patients are required, considering that PLR, NLR and LMR will be key markers in the clinical management of patients with gastric cancer.

The purpose of this study was to establish a correlation between markers of inflammation and the risk of rectal stenosis or obstruction, in patients with rectal adenocarcinomas. We performed a retrospective observational study on 188 patients diagnosed with rectal adenocarcinomas. We attempted to establish a correlation between the neutrophils to lymphocyte ratio(NLR), platelet to lymphocyte ratio(PLR) levels and the presence of rectal stenosis or rectal obstruction. From 188 patients included in the study, 65 patients had stenotic tumors (34.57% of cases) and 10 patients had occlusive tumors (5.31% of cases). We obtained a statistically significant correlation between the blood levels of neutrophils, lymphocytes, platelets, and the existence of rectal stenosis. (p[0.05). The cutoff value of NLR that correlates with the presence of rectal stenosis was 2.5 (95% CI: 0.426-0.574, AUC: 0.500). As for PLR, the cutoff value correlated with the presence of rectal stenosis was 106,522 (95%CI: 0.428-0.575, AUC: 0.502). We established a statistically significant correlation between NLR, PLR and rectal obstruction (p[0.05). The cutoff value of the NLR that correlates with the presence of rectal obstruction was 4.633 (95%CI: 0.614-0.751, AUC: 0.685). As for PLR, the cutoff value correlated with the presence of rectal stenosis was 345.05 (95% CI: 0.673-0.803, AUC: 0.742). Our study shows that there is a statistically significant correlation between NLR and PLR and the risk of rectal obstruction in patients with adenocarcinomas. It is still necessary to conduct prospective studies on much larger lots of patients to determine the NLR and PLR values that can predict rectal stenosis as well as rectal obstruction.

Background Rational use of medications and monitoring of prescriptions in elderly patients is important to decrease the number and duration of hospitalizations, emergency medical consultations, mortality, as well as medical costs. Purpose To identify potentially inappropriate medications (PIMs) and potential prescription omissions (PPOs), and determine their prevalence based on the Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) v2 criteria and Screening Tool to Alert doctors to Right Treatment (START) v2 criteria for patients aged >65 years. Methods This cross-sectional study was conducted in two rural counties in Romania based on electronic prescriptions for chronic conditions (EPCCs) issued from 30 days to 90 days by a specialist or general practitioner. Collected EPCCs were evaluated by an interdisciplinary team of specialists based on 26 STOPP v2 criteria and 10 START v2 criteria. Results PIM prevalence was 25.80% and PPO prevalence was 41.72% for 646 EPCCs. The mean age of patients was 75 years and the mean number of drugs per EPCC was four. The most frequently identified PIMs were treatment duration (6.65%), theophylline administration (5.72%), drug indication (4.64%), cyclo-oxygenase-2 non-steroidal anti-inflammatory drugs (1.39%), and zopiclone prescription (0.77%). Statins (24.76%), beta-blockers (8.04%), and beta-2 agonist/antimuscarinic bronchodilators (5.88%) were the most frequently identified PPOs. Conclusion PPOs were more prevalent than PIMs for elderly populations living in the two rural counties in Romania we studied. Health practitioners (family physicians, specialists, and pharmacists) should focus on prophylactic and curative considerations when prescribing agents to decrease the morbidity and mortality of elderly rural Romanian patients.

An 46-year-old Caucasian woman was diagnosed with idiopathic intracranial hypertension (IIH) after presenting with papilledema and bilateral visual blurring. Lumbar puncture revealed an opening pressure of more than 550 mmH2O. Cerebral magnetic resonance imaging (MRI) showed bilateral flattening of the posterior sclera, enhancement of the prelaminar optic nerve, distension of the perioptic subarachnoid space, intraocular protrusion of the prelaminar optic nerve and empty sella. The main purpose of the treatment was to release the symptoms and preserve the vision. It was initiated the general treatment with Mannitol 20%, 250 ml/day, Acetazolamide 2x500 mg/day and B-vitamins. After discharge the patient followed a treatment with acetazolamide 2x250 mg/ daily doses and oral potassium supplements 30 mg bid/day. Key words: pseudotumor cerebri, idiopatic intracranial hypertension, papilledema

PURPOSE We conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up. PATIENTS AND METHODS A total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)–positive tumors. RESULTS Pembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1–positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type). CONCLUSION In resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

Importance: Whether immune-related adverse events (irAEs) indicate drug activity in patients treated with immune checkpoint inhibitors remains unknown.Objective: To investigate the association between irAEs and recurrence-free survival (RFS) in the double-blind EORTC 1325/KEYNOTE-054 clinical trial comparing pembrolizumab therapy and placebo for the treatment of patients with high-risk stage III melanoma.Design, Setting, and Participants: A total of 1019 adults with stage III melanoma were randomly assigned on a 1:1 ratio to receive treatment with pembrolizumab therapy or placebo. Eligible patients were adults 18 years and older with complete resection of cutaneous melanoma metastatic to lymph nodes, classified with stage IIIA (at least 1 micrometastasis measuring >1 mm in greatest diameter), IIIB, or IIIC (without in-transit metastasis) cancer. Patients were randomized from August 26, 2015, to November 14, 2016. The clinical cutoff for the data set was October 2, 2017. Analyses were then performed on the database, which was locked on November 28, 2017.Interventions: Participants were scheduled to receive 200 mg of pembrolizumab or placebo every 3 weeks for a total of 18 doses for approximately 1 year or until disease recurrence, unacceptable toxic effects, major protocol violation, or withdrawal of consent.Main Outcomes and Measures: The association between irAEs and RFS was estimated using a Cox model adjusted for sex, age, and AJCC-7 stage, with a time-varying covariate that had a value of 0 before irAE onset and 1 after irAE onset.Results: Of 1011 patients who began treatment with pembrolizumab therapy or placebo, 622 (61.5%) were men and 389 (38.5%) were women; 386 patients (38.2%) were aged 50 to 64 years, 377 (37.3%) were younger than 50 years, and 248 (24.5%) were 65 years and older. Consistent with the reported main analysis in the intent-to-treat population, RFS was longer in the pembrolizumab arm compared with the placebo arm (hazard ratio [HR], 0.56; 98.4% CI, 0.43-0.74) among patients who started treatment. The incidence of irAEs was 190 (37.4%) in the pembrolizumab arm (n = 509) and 45 (9.0%) in the placebo arm (n = 502); in each treatment group, the incidence was similar for men and women. The occurrence of an irAE was associated with a longer RFS in the pembrolizumab arm (HR, 0.61; 95% CI, 0.39-0.95; P = .03) in both men and women. However, in the placebo arm, this association was not significant. Compared with the placebo arm, the reduction in the hazard of recurrence or death in the pembrolizumab arm was greater after the onset of an irAE than without or before an irAE (HR, 0.37; 95% CI, 0.24-0.57 vs HR, 0.61; 95% CI, 0.49-0.77, respectively; P = .03).Conclusions and Relevance: In this study, the occurrence of an irAE was associated with a longer RFS in the pembrolizumab arm.Trial Registrations: ClinicalTrials.gov identifier: NCT02362594; EudraCT identifier: 2014-004944-37.

Although benefiting from an unprecedented technological evolution, contemporary endodontics is still characterized by the recurrence of retreatments, due to the need to solve quite frequent incidents, accidents, or even failures of primary endodontic treatment. This survey aims to assess both the etiology and the prevention methods of one of the most troublesome endodontic iatrogenies: instrument separation during root canal shaping. The multifactorial nature of this occurrence entails identifying and taking into account all the causal and contributing factors. Their significant number and the possible involvement of any of them, starting with the complexity and variability of the root canals and ending with the technical specifications concerning the nickel-titanium rotary instrumentation system being used, highlight the necessity to develop valid guidelines to avert the occurring of such an upsetting situation.

The associations between periodontitis and cardiovascular diseases have been intensely studied in recent years. Oxidative stress is involved in the initiation and both progression of periodontitis and atherosclerosis. Antioxidants can reduce the effects of oxidative stress on inflammatory diseases. Our aim was to measure the effects of a grape seed extract (GSE), rich in antioxidants, on atherosclerosis caused by ligature-induced periodontitis in rats. Thirty male Wistar rats were randomly divided into three groups of 10: control group, periodontitis group, and periodontitis group treated with GSE (GSE group). Periodontitis was induced by placing an orthodontic wire around the cervix of the first mandibular molar and keeping it in place for 4 weeks. On days 1, 7 and 28, blood samples were taken to assess oxidative stress and inflammation markers (malondialdehyde and glutathione - MDA, reduced glutathione - GSH, C reactive protein) and lipids. After 4 weeks, the animals were euthanized, and aortas were collected for histopathologic examination. MDA was significantly higher in Periodontitis group compared to the other groups only at day 7. GSH was significantly increased in the Control and GSE groups on days 1 and 7, compared to Periodontitis group and on day 28 higher in GSE vs. Periodontitis groups. C reactive protein was significantly increased in the Periodontitis group on days 1 and 7 compared to both groups. Cholesterol was significantly decreased in the aortas of GSE group at day 28 compared to the Periodontitis group. Oral administration of a grape seed extract reduces the oxidative stress, inflammation and atherosclerosis in a rat model of ligature-induced periodontitis.

This study aims to analyze the performance of rotary root canal preparation, conducted by beginner operators (students). After acquiring the necessary skills involved in applying endodontic preparation techniques on extracted teeth, all students from a cohort learned to use ProTaper Universal files (Dentsply Maillefer). The preclinical training had several stages. Experience 1: instrumentation on extracted single-root teeth; Experience 2: instrumentation on EndoTraining blocks (Dentsply Maillefer); Experience 3: instrumentation on EndoTraining blocks (Dia Dent Group International); Experience 4: Instrumentation on extracted multiradicular teeth. Preparation was done according to the manufacturer’s instructions, the initial file is Sx, followed by S1, S2, F1, F2 and the last file is F3. A batch of 50 teeth (E1, E2, E3, E4) was randomly selected to evaluate the onset of the rotary preparation of young operators. Two independent evaluators analyzed the array radiologically by stereomicroscope evaluation (E1, E4) and photo-analysis of the resulting Endo Training blocks (E2, E3). The success rate was 80% for E1, 72% for E2, 64% for E3 and 76% for E4 (p Endodontic instrumentation techniques require training to acquire the necessary skills. Rotary root canal instrumentation techniques used almost exclusively in modern endodontics require adequate preclinical training.

Heart failure is still the leading cause of hospitalization in patients over 65 years of age and is defined as a multifactorial pathology which involves environmental factors and also genetic predispositions. The aim of the present study was to evaluate a possible correlation between single nucleotide polymorphisms (SNPs) of angiotensin converting enzyme 2 (ACE2) and monocyte chemoattractant protein-1 (MCP-1) genes and cardiac remodeling in Caucasian patients diagnosed with heart failure. Our comparative translational research study included 116 patients diagnosed with heart failure and was carried out in Cluj-Napoca, Romania between September 2017 and March 2019. Three SNPs, namely rs4646156, rs4646174 and rs1024611, were genotyped using a Taqman real-time PCR technique. Our results showed that carriers of the AA genotype for ACE2 rs4646156 had a significant dilatation of the left ventricle (LV) with signs of LV hypertrophy (LVH), while TT carriers had a significant left atrial dilatation. For ACE2 rs4646174, homozygotes for the C allele presented a dilated LV with signs of LVH with statistical significance and had a tendency towards a lower ejection fraction. MCP-1 rs1024611 AA variant carriers had a significant LVH in the dominant model. In conclusion, our study showed a strong association between echocardiographic parameters of cardiac remodeling and SNPs rs4646156, rs4646174 of ACE2 and rs1024611 of MCP-1.

Background: We investigated the correlation between the androgen receptor (AR) and immunohistochemistry (IHC) as a prognostic factor in breast cancer (BC). AR is expressed in 60–80% of BC. Methods: We evaluated the prognostic values of AR expression among 143 patients with BC for 36 months. The protocol was amended to measure androgen, estrogen and progesterone receptor expression by IHC and the percentage of hormone positive nuclei was quantified. We determined and quantified the Her2/neu status using IHC and in situ hybridization. The methodology consisted in using a Kaplan–Meier analysis and restricted mean survival time up to 36 months. The principal endpoints of the study were overall survival (OS) and progression free survival (PFS). Results: 57 % of patients (n = 82) from our group had AR+ (≥ 1%). Patients with AR+ had better OS, 35.50 vs. 33.40 months, with p = 0.027. Moreover, PFS was prolonged for patients AR+, 32.60 vs. 30.50 months, with p = 0.38. Triple negative breast cancer (TNBC) patients had lower OS and no difference was observed for PFS. Conclusions: Both OS and PFS were favorably influenced by the presence of AR. TNBC had worse outcomes compared with patients with hormonal or/and Her 2/neu positive disease in terms of OS.

Introduction. In recent years a link between periodontitis and cardiovascular diseases has been proposed. Oxidative stress has been found to be involved in their pathophysiology. Objectives. The aim of this study was to demonstrate that a wire ligature placed around the first mandibular molars of the rat causes inflammation in the periodontium and lipid deposits in the aorta, via oxidative stress. Methods. Twenty male Wistar rats were divided randomly into two groups of 10: Control group and Periodontitis group. An orthodontic wire ligature was placed around the cervix of the first mandibular molar and was kept in place for 4 weeks. Clinical attachment loss was determined to assess the gingival recession. Aorta was harvested after 4 weeks and the malondialdehyde (MDA) levels in the aorta tissue homogenate were determined. Lipid deposits were evaluated using Oil Red staining and immunofluorescence under confocal microscopy. Total lipid deposits in the aorta were assessed using a computer morphometry system. Results. Significant gingival recession was observed in the Periodontitis group in comparison with the Control group. Increased MDA levels were present in the aorta in the ligatured rats in comparison with the Control group. Significant lipid deposits were observed in the aorta of the Periodontitis group as opposed to the Control group. Conclusions. The affixing of an orthodontic wire ligature produces gingival recession, increased oxidative stress and lipid deposits in the rat descending aorta.

Background: Lymph node status in gastric cancer is known as an independent prognostic factor that guides the surgical and oncological treatment and independently influences long-term survival. Several studies suggest that the lymph node ratio has a greater importance in survival than the number of metastatic lymph nodes. Aim: The aim of this study was to evaluate the clinical and morphological factors that can influence the survival of gastric cancer patients, with an emphasis on nodal status and the lymph node ratio. Material and methods: We conducted a retrospective study in which 303 patients with gastric cancer admitted to the Department of Surgery of the Mureș County Hospital between 2008 and 2018 were screened for study enrolment. Data were obtained from the records of the department and from the histopathological reports. The examined variables included: age, gender, tumor localization, T stage, histological type, grade of differentiation, surgical procedure, lympho-vascular invasion, excised lymph nodes, metastatic lymph nodes, lymph node ratio. After screening, the study included a total number of 100 patients, for which follow-up data was available. Results: The mean age of the study population was 66.43 ± 10 years, and 71% were males. The average survival period was 21.42 months. Statistical analysis showed that the localization of the tumor (p = 0.021), vascular invasion (p ---lt---0.001), T (p = 0.004) and N (p ---lt---0.001) stages, type of surgery (partial gastrectomy 59% vs. total gastrectomy 41%, p = 0.005), as well as the lymph node ratio (p ---lt---0.001) were prognostic factors for survival in patients with gastric cancer undergoing surgical therapy. Conclusions: The survival of gastric cancer patients is significantly influenced by tumor localization, T stage, vascular invasion, type of surgery, N stage and the lymph node ratio based on univariate analysis. Also, the lymph node ratio proved to be an independent prognostic factor for survival.

Background: In the phase III double-blind European Organisation for Research and Treatment of Cancer 1325/KEYNOTE-054 trial, pembrolizumab improved recurrence free and distant metastasis-free survival in patients with stage III cutaneous melanoma with complete resection of lymph nodes. In the pembrolizumab group, the incidence of grade I-V and of grade III-V immune-related adverse events (irAEs) was 37% and 7%, respectively. Methods: Patients were randomised to receive intravenous (i.v.) pembrolizumab 200 mg (N = 514) or placebo (N = 505) every 3 weeks, up to 1 year. On recurrence, patients could enter part 2 of the study: pembrolizumab 200 mg i.v. every 3 weeks up to 2 years, for crossover (those who received placebo) or rechallenge (those who had recurrence >6 months after completing 1-year adjuvant pembrolizumab therapy). For these patients, we present the safety profile and efficacy outcomes. Results: At the clinical cut-off (16-Oct-2020), in the placebo group, 298 patients had a disease recurrence, in which 155 (52%) crossed over ('crossover'). In the pembrolizumab group, 297 patients completed the 1-year treatment period; 47 had a recurrence >6 months later, in which 20 (43%) entered the rechallenge part 2 ('rechallenge'). In the crossover group, the median progression-free survival (PFS) was 8.5 months (95% confidence interval [CI] 5.7-15.2) and the 3-year PFS rate was 32% (95% CI 25-40%). Among 80 patients with stage IV evaluable disease, 31 (39%) had an objective response: 14 (18%) patients with complete response (CR) and 17 (21%) patients with partial response. The 2-year PFS rate from response was 69% (95% CI 48-83%). In the rechallenge group, the median PFS was 4.1 months (95% CI 2.6-NE). Among 9 patients with stage IV evaluable disease, 1 had an objective response (CR). Among the 175 patients, 51 (29%) had a grade I-IV irAE and 11 (6%) had a grade III-IV irAE. Conclusions: Pembrolizumab treatment after crossover yielded an overall 3-year PFS rate of 32% and a 39% ORR in evaluable patients, but the efficacy (11% ORR) was lower in those rechallenged. (c) 2021 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background and objectives: Our aim is to explore the relationship between the levels of protein encoded by Ki67 and the histopathological aspects regarding the overall survival and progression-free survival in a single university center. A secondary objective was to examine other factors that can influence these endpoints. New approaches to the prognostic assessment of breast cancer have come from molecular profiling studies. Ki67 is a nuclear protein associated with cell proliferation. Together with the histological type and tumor grade, it is used to appreciate the aggressiveness of the breast tumors. Materials and Methods: We conducted a retrospective single-institution study, at Elias University Emergency Hospital, Bucharest, Romania, in which we enrolled women with stage I to III breast cancer. The protocol was amended to include the immunohistochemistry determination of Ki67 and the histological aspects. The methodology consisted in using a Kaplan&ndash, Meier analysis for the entire sample and restricted mean survival time up to 36 months. Results: Both lower Ki67 and low tumor grade are associated with better prognosis in terms of overall survival (OS) and progression-free survival (PFS) for our patients&rsquo, cohort. In our group, the histological type did not impact the time to progression or survival. Conclusions: Both overall survival and progression-free survival may be influenced by the higher value of Ki67 and less differentiated tumors. Further studies are needed in order to establish if the histologic type may impact breast cancer prognostic, probably together with other histologic and molecular markers.

Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrine disorder in women of reproductive age. Vitamin D and its receptor are thought to play an important role in PCOS susceptibility, although the impact of vitamin D receptor (VDR) polymorphisms on the hormonal and metabolic profile is still controversial. A literature search in PubMed and Embase was performed up to September 2020 for case-control studies in women suffering from PCOS, with outcome related to VDR polymorphisms effect on metabolic/endocrine disturbances. We have found 16 eligible studies including 2566 women with PCOS and 2430 controls. ApaI polymorphism seemed to be associated with hyperandrogenism in both Asian and Caucasian population. FokI variant was correlated with metabolic/endocrine parameters especially in Asian population, while a relation between Cdx2 genotypes and insulin sensitivity was observed in both ethnicities. VDR polymorphisms have an important role in PCOS development and related hormonal and metabolic abnormalities. Few case-control studies analysed the interaction between VDR variants and metabolic/endocrine parameters with the majority of the articles focused on the Asian region. Further research on various ethnic populations with larger sample size are still needed for a definitive conclusion, in order to allow early diagnosis and prevention of PCOS comorbidities.

Background: Hypertension and left ventricular hypertrophy (LVH) are most important contributors to left ventricular diastolic dysfunction (DD), left atrial remodeling and atrial fibrillation. Objectives: The primary goal is to compare left atrial (LA) remodelling and left ventricular DD in patients with or without paroxysmal atrial fibrillation (PAF) and with or without essential hypertension (HTN). Materials and Method: The study comprised 128 patients with normal left ventricular systolic function (LVEF\(\ge\)50%). They were divided into two groups based on the presence or absence of essential hypertension. The normotensive individuals (n=65) were split into two groups: PAF (n=32) and control no-PAF (n=33).The hypertensive individuals were further split into two groups: PAF (n=32) and control no-PAF (n=31). The patients in the control group were chosen to match the PAF groups in terms of gender, age, and weight. Resting 12 lead ECG, 24 hour Holter ECG monitoring, 24 hour blood pressure monitoring, and 2D Doppler echocardiography were used to evaluate the patients. The follow-up was done every six months for three years. The MedCalc 12.3.0.0 statistical software for Windows was used for the statistical analysis. When the p-value was less than 0.05, the results were considered statistically significant. Results and Conclusion: PAF patients have larger LA diameters. HTN causes an increase in supplemental LA.The number of PAF episodes has no effect on LA diameters. The gender of the patients has little effect on the statistical data, with larger diameters in PAF and HTN patients.

This chapter deals with the emergency treatment of transverse colon cancer. The main complications that classify transverse colon cancer in an emergency setting are obstruction, perforation accompanied by localized or generalized peritonitis, and hemorrhage which may be occult or cataclysmic with hemorrhagic shock. We present the technical principles of radical surgical resection using embryological, anatomical, and oncological concepts. In this chapter we also discuss the principles of lymphadenectomy associated with complete excision of the mesocolon with high vascular ligation, in particular with T3 or T4 cancers requiring D2/D3 lymphadenectomy. The use of infrapyloric, gastro-epiploic, and prepancreatic lymphadenectomy is recommended due to the frequent metastases in these regional lymph nodes.

Rectal cancer is one of the most common types of cancer in both men and women. In recent years, the importance of magnetic resonance imaging (MRI) has greatly increased in the multidisciplinary treatment of patients with rectal cancer. MRI has a particularly important role in the most accurate preoperative staging of these patients, both in terms of assessing the local invasion of the tumor and in terms of assessing the status of pelvic lymph nodes. Many patients with rectal cancer, especially those in the advanced stage of the disease, in the preoperative period undergo neoadjuvant radio chemotherapy. The evaluation of the clinical response of these patients to neoadjuvant therapy is of crucial importance both in terms of personalized treatment and in terms of their prognosis. In this regard, MRI has its clearly defined role at present in evaluating the efficacy of neoadjuvant therapy, as well as in postoperative follow-up.

Introduction: Pediatric patients with cardiac congenital diseases require heart valve implants that can grow with their natural somatic increase in size. Current artificial valves perform poorly in children and cannot grow; thus, living-tissue-engineered valves capable of sustaining matrix homeostasis could overcome the current drawbacks of artificial prostheses and minimize the need for repeat surgeries.Materials and Methods: To prepare living-tissue-engineered valves, we produced completely acellular ovine pulmonary valves by perfusion. We then collected autologous adipose tissue, isolated stem cells, and differentiated them into fibroblasts and separately into endothelial cells. We seeded the fibroblasts in the cusp interstitium and onto the root adventitia and the endothelial cells inside the lumen, conditioned the living valves in dedicated pulmonary heart valve bioreactors, and pursued orthotopic implantation of autologous cell-seeded valves with 6 months follow-up. Unseeded valves served as controls.Results: Perfusion decellularization yielded acellular pulmonary valves that were stable, no degradable in vivo, cell friendly and biocompatible, had excellent hemodynamics, were not immunogenic or inflammatory, non thrombogenic, did not calcify in juvenile sheep, and served as substrates for cell repopulation. Autologous adipose-derived stem cells were easy to isolate and differentiate into fibroblasts and endothelial-like cells. Cell-seeded valves exhibited preserved viability after progressive bioreactor conditioning and functioned well in vivo for 6 months. At explantation, the implants and anastomoses were intact, and the valve root was well integrated into host tissues; valve leaflets were unchanged in size, non fibrotic, supple, and functional. Numerous cells positive for a-smooth muscle cell actin were found mostly in the sinus, base, and the fibrosa of the leaflets, and most surfaces were covered by endothelial cells, indicating a strong potential for repopulation of the scaffold.Conclusions: Tissue-engineered living valves can be generated in vitro using the approach described here. The technology is not trivial and can provide numerous challenges and opportunities, which are discussed in detail in this paper. Overall, we concluded that cell seeding did not negatively affect tissue-engineered heart valve (TEHV) performance as they exhibited as good hemodynamic performance as acellular valves in this model. Further understanding of cell fate after implantation and the timeline of repopulation of acellular scaffolds will help us evaluate the translational potential of this technology.

Introduction: Hydatid disease is a parasitic disease caused by and is commonly met in clinical practice. The most common location for hydatic cysts is the liver, while the lung is the second organ in terms of localization frequency. Case report: We present the case of a 40-year-old patient with pulmonary hydatid cysts (two hydatid cysts located in the upper and lower pulmonary left lobes), and multiple hepatic hydatid cysts (ten cysts located in both hepatic lobes). Initially, the patient underwent thoracic surgery and was subjected to atypical lung resection of the upper and lower left pulmonary lobes. The patient underwent surgical treatment of the hepatic hydatid cysts 6 months after the thoracic surgery. The patient underwent multiple partial cystectomies, cholecystectomy, Kehr drainage with two hepatic hydatid cysts showing biliary fistulas. The postoperative evolution was favorable with patient discharge 10 days following surgery. Conclusions: Although the hepatic hydatid cyst is a seemingly benign disease, there are complex cases of disseminated echinococcosis in clinical practice that may require complex treatment. Surgical treatment remains the best therapeutic option in these cases. Thus, for these patients, a careful postoperative follow-up is required to detect recurrence of hydatid disease.

Funding Acknowledgements This work was supported by the University of Medicine, Pharmacy, Science and Technology of Targu Mures Research Grant number 615/13/17.01.2019 Background An early appearance of cardiac masses after valve replacement raises differential diagnosis problems. The specific therapeutic approach of autoimmune comorbidities enhances the risk of infective endocarditis or inflammatory reactions. Among systemic disorders leading to cardiac complications, rheumatoid arthritis is cited. Leflunomide is a synthetic disease-modifying antirheumatic drug (DMARD) with immunomodulatory actions as it inhibits the de novo synthesis of pyrimidine, hence suppressing T cell activation and proliferation. It is used as first line treatment strategy for rheumatoid arthritis (RA) patients, with contraindication or non-tolerance of Methotrexate. Case presentation We present the case of a 63-year old Caucasian male with seropositive RA, treated with Leflunomide 20 mg od, with history of severe calcified aortic stenosis and permanent atrial fibrillation. The patient underwent an aortic valve replacement with a St. Jude Regent 25 mechanical valve and ascending aorta replacement with a Dacron 30mm graft. Leflunomide was forthwith discontinued before surgery. Five months after surgery, in a routine check-up, including proper adherence to the anticoagulation regimen (regular INR 2.6-3.2), and stable hemodynamic status, a right atrial mass was identified by transthoracic echocardiography (figure). The mobile hyperechogenic mass appeared to be attached by a narrow stalk to the atrial septum, presenting a quasi-parallel movement to the septal cusp. The haemodynamic of the tricuspid valve was not affected. A suspicion of early infective endocarditis was ruled out. Cardiac CT identified a well-defined, pedunculated, mobile mass measuring 2.8x3.1 cm originating above the tricuspid annulus, attached to the atrial septum without hemodynamic impact. An inflammatory pseudotumor was identified and a granulomatous mass was diagnosed. Consecutively, Leflunomide 20 mg od along with adjusted doses of corticosteroids were initiated with progressively diminished dimensions of the tumour three months after the ultrasound and CT diagnosis. One year after complete resolution of the mass, the patient continues his immunosuppressive and cardiac pharmacological regimen. Repeated echocardiograms showed standard functionality of the aortic prosthesis, without recurrent intracardiac mass. Conclusion Management of an intracardiac mass after cardiac surgery in patients with systemic inflammatory diseases may be challenging. Cardiac imaging is mandatory to differentiate among thrombi, vegetations, primary or metastatic cardiac tumours. In RA patients DMARD and immunosuppressive therapy should not be discontinuing during perioperative procedures as they do not increase the risk of infectious complications. Sequential imaging studies in patients presenting systemic inflammatory comorbidities should be used to assess and identify the immunological responses in the absence of targeted therapy. Abstract P1454 Figure.

Nasopharyngeal carcinoma (NPC) is a rare form of malignancy, accounting for 2% of all cancers of the head and neck in Europe. Axillary lymph node metastases are very rare in these cases. This is a case report of a 40-year-old premenopausal woman diagnosed in May 2015 with T1N2M0 stage III NPC, treated with induction chemotherapy, followed by chemo-radiotherapy. Post-therapeutic computed tomography (CT) scan showed partial response (PR) on the primary tumor and complete response (CR) on the latero-cervical lymph nodes. In 2017, our patient developed left carcinomatous-like mastitis with axillary lymphadenopathy. This raised suspicions of a carcinomatous mastitis. The pathology report with immunohistochemistry (IHC) of the third biopsy highlighted axillary metastasis of a non-keratinizing squamous cell carcinoma (NSCC). There are very few references in the literature regarding axillary metastases from squamous cell carcinoma of the head and neck (HNSCC). As far as we know, this is the first case report of mastitis due to NPC. To conclude, treatment consisted of two surgical excisions of axillary lymphadenopathy associated with local radiotherapy and chemotherapy (neo-adjuvant, adjuvant). The second surgery, performed after radiotherapy, required plastic surgery. A psychiatric evaluation was necessary, revealing a reactive anxiety disorder. This case required multidisciplinary management, where oncology, plastic surgery, pathology and psychiatric specialists collaborated in deciding the therapeutic approach.

Melanomas of the skin are poorly circumscribed lesions, very frequently asymptomatic but unfortunately with a continuous growing incidence. In this landscape, one can distinguish melanomas originating in the mucous membranes and located in areas not exposed to the sun, namely the vulvo-vaginal melanomas. By contrast with cutaneous melanomas, the incidence of these types of melanomas is constant, being diagnosed in females in their late sixties. While hairy skin and glabrous skin melanomas of the vulva account for 5% of all cancers located in the vulva, melanomas of the vagina and urethra are particularly rare conditions. The location in areas less accessible to periodic inspection determines their diagnosis in advanced stages, often metastatic. Moreover, despite the large number of drugs newly approved in recent decades for the treatment of cutaneous melanoma, especially in the category of biological drugs, the mortality of vulvo-vaginal melanomas has remained almost constant. This, together with the absence of specific treatment guidelines due to the lack of a sufficient number of cases to conduct randomized clinical trials, makes melanomas with this localization a discouraging diagnosis, associated with a very poor prognosis. Our aim is therefore to draw attention to this oftentimes overlooked entity in order to encourage the community to employ various strategies meant to increase research in this area. By highlighting the main risk factors of vulvar and vaginal melanomas, as well as the clinical manifestations and molecular changes underlying these neoplasms, ideally novel therapeutic schemes will, in time, be brought into effect.

Ovarian cancer is one of the most common causes of death in women as survival is highly dependent on the stage of the disease. Ovarian cancer is typically diagnosed in the late stage due to the fact that in the early phases is mostly asymptomatic. Genomic instability is one of the hallmarks of ovarian cancer. While ovarian cancer is stratified into different clinical subtypes, there still exists extensive genetic and progressive diversity within each subtype. Early detection of the disorder is one of the most important steps that facilitate a favorable prognosis and a good response to medical therapy for the patients. In targeted therapies, individual patients are treated by agents targeting the changes in tumor cells that help them grow, divide and spread. Currently, in gynecological malignancies, potential therapeutic targets include tumor-intrinsic signaling pathways, angiogenesis, homologous-recombination deficiency, hormone receptors, and immunologic factors. Ovarian cancer is usually diagnosed in the final stages, partially due to the absence of an effective screening strategy, although, over the times, numerous biomarkers have been studied and used to assess the status, progression, and efficacy of the drug therapy in this type of disorder.