Assessment of the Particularities of Thrombophilia in the Management of Pregnant Women in the Western Part of Romania.

Background and objectives: Thrombophilia in pregnant women is a condition whose incidence is constantly increasing worldwide, and, under these conditions, the development of preventive procedures is becoming essential. In this study, we aimed to evaluate thrombophilia in pregnant women in the western part of Romania and to establish anthropometric characteristics, socioeconomic features, and genetic and risk factors. Material and Methods: 178 pregnant women were divided into three study groups, according to the type of thrombophilia, aiming to carry out the genetic profile and the acquired one. Anthropometric measures and biological tests were performed. Results: The mixed type of thrombophilia predominates. The particularities of pregnant women diagnosed with thrombophilia are higher age, living in an urban environment, with normal BMI, approximately 36 weeks of gestational period, and having at least one miscarriage. Regarding the most frequent thrombophilic genetic markers, we obtained the MTFHR gene mutation C677T and A1298C, followed by the PAI-1 4G/5G gene mutation. Smoking represents an aggravating factor in the evolution of this pathology, manifested through the increase of D-dimers and the decrease in antithrombin values, simultaneously with the increase in therapeutic need. Conclusions: The predominance of MTHFR and PAI-1 4G/5G gene polymorphism is a particularity of pregnant women with thrombophilia from the western part of Romania. Smoking is confirmed as an important risk factor in spontaneous abortion.

Approach to Thrombophilia in Pregnancy-A Narrative Review.

Thrombophilia is a genetic predisposition to hypercoagulable states caused by acquired haemostasis conditions; pregnancy causes the haemostatic system to become hypercoagulable, which grows throughout the pregnancy and peaks around delivery. Genetic testing for thrombophilic gene mutations is evaluated using different methodologies of real-time polymerase chain reaction and DNA microarrays of specific genes. Adapting the general care of the pregnant woman to the particularities caused by thrombophilia is an important component, so screening is preferred to assess the degree of genetic damage that manifests itself as a risk of thrombosis. The major goal of this narrative review was to quantitatively evaluate the literature data on the specific care of pregnant women with thrombophilia that are at risk of developing unplanned miscarriages.

A sequential assessment of the preservation injury in porcine intestines.

BACKGROUND: Clinical and experimental evidence strongly suggest that ischemia-reperfusion injury after intestinal transplantation has deleterious short- and long-term effects and finding means to reduce ischemia-reperfusion injury is a major research area. The anatomical and physiological similarities between the human and porcine digestive tract favor its use as a preclinical model for translational research. Intriguingly, no systematic appraisal of the development of the intestinal preservation injury in pigs is available. MATERIALS AND METHODS: Intestinal procurement was performed in nine pigs using histidine-tryptophan-ketoglutarate solution as preservation fluid. Ileal biopsies were obtained after 8, 14, and 24 h of static cold storage (SCS), and the preservation injury was assessed morphologically (Chiu score) as well as on the molecular level. Tight junction (zonula occludens, claudin-3 and 4, tricellulin, and occludin) and adherens junctions (E-cadherin) proteins were studied using immunofluorescence and Western blot. RESULTS: Eight hours of SCS induced minimal mucosal changes (Chiu grade 1) that advanced to significant subepithelial edema (Chiu grade 3) after 24 h; progressive Goblet cell depletion was also noted. Apoptosis (studied by cleaved caspase-3 staining significantly increased after 24 h of SCS. Significant molecular changes with decreasing expression of zonula occludens, tricellulin, and occludin were evident already after 8 h of SCS and continuously worsened. Claudin-3 and Claudin-4 and E-cadherin expression remained relatively unaltered during SCS. CONCLUSIONS: Important molecular alterations precede histologic changes during SCS of the porcine intestine and may be used as more sensitive injury markers than histologic changes in intestinal ischemia and transplantation.

Casting Light on Early Heart Failure: Unveiling the Prognostic Potential of the E/(e' × s') Index.

It has been shown that patients with NYHA class I and II have a high morbidity and mortality burden. We investigated the value of a new tissue Doppler index, E/(e' × s'), to predict cardiac events in the long-term follow-up of patients at an early stage of heart failure (HF). Sequential echocardiography was conducted on a consecutive cohort of 212 hospitalized HF patients, pre-discharged and with three-month follow-up. The primary end point consisted of cardiac death or readmission due to HF worsening. During follow-up, cardiac events occurred in 99 patients (46.7%). The first cardiac event was represented by cardiac death in 8 patients (3.8%) and readmission for HF in 91 patients (42.9%). A Kaplan-Meier analysis did not show a significantly different event-free survival rate between patients with NYHA class I and II. The composite end point was significantly higher in patients with an E/(e' × s') >1.6. The E/(e' × s') at discharge was the best independent predictor of cardiac events. Those exhibiting an E/(e' × s') > 1.6 at discharge, with a subsequent deterioration after three months, displayed the poorest prognosis concerning cardiac events, HF-related rehospitalization, and cardiac mortality (all p < 0.05). In early-stage HF patients, an E/(e' × s') > 1.6 emerged as a robust predictor of clinical outcomes, especially when coupled with a deterioration in condition.

Hindpaw withdrawal from a painful thermal stimulus after sciatic nerve compression and decompression in the diabetic rat.

INTRODUCTION: Although the effect of chronic compression and surgical decompression of the diabetic rat sciatic nerve has been evaluated by walking track analysis, the measurement of sensory function by response to thermal nociceptive stimulation has not been investigated. METHODS: Fifteen male Wistar rats with streptozotocin-induced diabetes underwent sciatic nerve compression through a 10-mm silicone band. Five rats had histology done 60 days after confirming chronic nerve compression. Pain threshold was measured using hindlimb withdrawal times (HLWT) from a heat stimulus. After 60 days of compression, the silicone tube was removed. Five nondiabetic, nonbanded rats were used as controls. RESULTS: Control mean HLWT was 9.7 ± 1.5 sec. In the diabetes group (60 days of compression), mean HLWT was 23.6 ± 2.4 sec. (p < 0.001). Thirty days after removal of the silicone, mean HLWT to painful stimuli was 14.9 ± 1.5 sec. (p < 0.001). CONCLUSION: Chronic compression of the diabetic rat sciatic nerve increases (worsens) the threshold to heat (pain) perception. Decompression reverses this effect (improves nociception).

Attitude of Romanian Medical Students and Doctors toward Business Ethics: Analyzing the Influence of Sex, Age, and Ethics Education.

This study investigated the attitude of Romanian medical students and doctors toward business ethics by measuring the preference for a particular ethical philosophy, namely, the preference for Machiavellianism, moral objectivism, social Darwinism, ethical relativism, and legalism. At the same time, this study aimed to explore the influence of sex, age, and ethics education on the attitude toward business ethics. The data collection was performed using a voluntary self-administered online survey including the Attitudes Toward Business Ethics Questionnaire (ATBEQ) instrument. Our findings show that the values based on which Romanian medical students and doctors make business decisions belong predominantly to the moral objectivism philosophy, which is grounded on rational actions based on a set of objective moral standards.

Maternal and Newborn Characteristics-A Comparison between Healthy and Thrombophilic Pregnancy.

A thrombophilic woman is more likely to experience difficulties during pregnancy, difficulties that will also affect the development of the newborn. This study aims to compare maternal and newborn characteristics between healthy and thrombophilic pregnancy. The following characteristics were analysed: maternal characteristics (BMI- body mass index, haemostasis parameters, thrombophilia-specific treatment) and newborn characteristics (gestational period, birth weight, the Apgar score). This follow-up study spanning five years, from 2018 to 2022, focuses on a cohort of 500 women who underwent delivery hospitalization in the western region of Romania. The maternal characteristics influence the newborn: the greater the weight of the mother with thrombophilia, the more the chances that the fetus will have a lower birth weight; increasing the dose of LMWH (low molecular weight heparin), connected with the necessity to control the homeostasis parameters, the more likely the fetus will be born with a lower birth weight. A pregnant woman with thrombophilia, treated appropriately, having a normal weight, and not presenting other risk factors independent of thrombophilia, will have a newborn with characteristics similar to a healthy pregnant woman.

Pregnancy in a Young Patient with Metastatic HER2-Positive Breast Cancer-Between Fear of Recurrence and Desire to Procreate.

Breast cancer is the most frequent neoplasm among women and the second leading cause of death by cancer. It is the most frequent cancer diagnosed during pregnancy. Pregnancy-associated breast cancer is defined as breast cancer that is diagnosed during pregnancy and/or in the postpartum period. Data about young women with metastatic HER2-positive cancer who desire a pregnancy are scarce. The medical attitude in these clinical situations is difficult and nonstandardized. We present the case of a 31-year-old premenopausal woman diagnosed in December 2016 with a stage IV Luminal HER2-positive metastatic breast cancer (pT2 N0 M1 hep). The patient was initially treated by surgery in a conservative manner. Postoperatively, the presence of liver metastases was found by CT investigation. Consequently, line I treatment (docetaxel l75 mg/m² iv; trastuzumab 600 mg/5 mL sq) and ovarian drug suppression (Goserelin 3.6 mg sq at 28 days) was administered. After nine cycles of treatment, the patient's liver metastases had a partial response to the therapy. Despite having a favorable disease evolution and a strong desire to procreate, the patient vehemently refused to continue any oncological treatment. The psychiatric consult highlighted an anxious and depressive reaction for which individual and couple psychotherapy sessions were recommended. After 10 months from the interruption of the oncological treatment, the patient appeared with an evolving pregnancy of 15 weeks. An abdominal ultrasound revealed the presence of multiple liver metastases. Knowing all the possible effects, the patient consciously decided to postpone the proposed second-line treatment. In August 2018, the patient was admitted in the emergency department with malaise, diffuse abdominal pain and hepatic failure. Abdominal ultrasound found a 21-week-old pregnancy which had stopped in evolution, multiple liver metastases and ascites in large quantity. She was transferred to the ICU department where she perished just a few hours later. Conclusions/Discussion: From a psychological standpoint, the patient had an emotional hardship to make the transition from the status of a healthy person to the status of a sick person. Consequently, she entered a process of emotional protection of the positive cognitive distortion type, which favored the decision to abandon treatment and try to complete the pregnancy to the detriment of her own survival. The patient delayed the initiation of oncological treatment in pregnancy until it was too late. The consequence of this delay in treatment led to the death of the mother and fetus. A multidisciplinary team worked to provide this patient with the best medical care and psychological assistance throughout the course of the disease.

The Pattern of Second Primary Tumours in Postmenopausal Women with Prior Breast Cancer in Western Romania: A Retrospective, Single-Institution Study.

With improved survival, more patients with prior breast cancer are at risk of having a second primary cancer diagnosed. The pattern and impact of second primary cancers following breast cancer is important for overall breast cancer therapeutic management. Our study is a first analysis of the trend of second primary tumours over time in terms of incidence, sites with significantly elevated risks and correlation with stage, molecular subtype and therapeutic strategies conducted in Eastern Europe in postmenopausal women with breast cancer. PATIENTS AND METHODS: Our study population included 28 patients with prior breast cancer (BC) and second primary tumours, which were diagnosed and treated in our Institution between 2004 and 2017. The criteria for selection were based on the completeness of the documentation of the first treatment for breast cancer, stage of disease, molecular subtype, the site of origin of the second tumours and the survival data. RESULTS: An increased risk of second primary cancer was associated with the 51-60 years age group (53.6%), with the greater prevalence in patients living in urban environments (82.1%). The use of chemotherapy increased the risk of the occurrence of gynecological second malignancies (75%). Our study is a first analysis of the trend of second primary tumours over time in terms of identifying sites with significantly elevated risks and correlation with therapeutic strategies conducted in Eastern Europe in postmenopausal women with breast cancer. CONCLUSIONS: Our study is a first analysis of the trend of second primary tumours over time in terms of correlation with luminal subtype and stage at diagnosis of primary cancer sites with significantly elevated risks and correlation with therapeutic strategies in postmenopausal women with breast cancer conducted in Eastern Europe. The reported time from primary to second primary malignancy onset, with a significantly higher rate for postmenopausal breast cancer patients, was less than one year (50%). With the advances and wider availability of genetic testing (e.g., gene panels), patients diagnosed with multiple primaries should be increasingly investigated for an underlying cancer predisposition. Postmenopausal women with breast cancer may benefit from increased surveillance and advice to avoid second malignancies.

Unilateral Orbital Metastasis as the Unique Symptom in the Onset of Breast Cancer in a Postmenopausal Woman: Case Report and Review of the Literature.

The orbit represents an unusual metastases site for patients diagnosed with cancer, however, breast cancer is the main cause of metastases at this level. These orbital metastases were discovered in patients with a history of breast cancer as unique or synchronous lesions. We present a rare case of a unique retroocular metastasis as the first initial symptom of a tubulo-lobular mammary carcinoma in a postmenopausal woman. A 57-year-old patient complains of diplopia, diminishing visual acuity, orbital tenderness, slight exophthalmia and ptosis of the left eyelid, with insidious onset. Clinical examination and subsequent investigations revealed a left breast cancer cT2 cN1 pM1 stage IV. Breast conserving surgery was performed on the left breast. Pathological examination with immunohistochemistry staining established the complete diagnostic: pT2pN3aM1 Stage IV breast cancer, luminal B subtype. After two years from the initial breast cancer diagnosis, the patient was diagnosed by the psychiatrist with a depressive disorder and was treated accordingly. Orbital metastases are usually discovered in known breast cancer patients and they are found in the context of a multi-system end-stage disease. Most reports cite that up to 25% of the total orbital metastases cases are discovered before the diagnosis of the primary tumor, as our case did. MRI is the gold standard for evaluating orbital tumors. The ILC histological subtype metastasizes in the orbitals more frequently than invasive ductal carcinoma. The prognosis of patients with orbital metastases is poor. The median survival after diagnosis of orbital metastases from a breast cancer primary is ranging from 22 to 31 months. Overall survival of our patient was 56 months, longer than the median survival reported in literature. Orbital metastases must be taken into account when patients accuse ophthalmologic symptoms even in the absence of a personal history of cancer. Objective examination of every patient that incriminates these types of symptoms is essential, and breast palpation must be made in every clinical setting. Orbital biopsy is necessary for the confirmation of the diagnosis and for an adequate treatment. Although recommendations for management of orbital metastases are controversial, it appears that multidisciplinary treatment of both metastases and primary cancer improves overall survival.

Postmenopausal Breast Cancer in Women, Clinical and Epidemiological Factors Related to the Molecular Subtype: A Retrospective Cohort Study in a Single Institution for 13 Years. Follow-Up Data.

This study focused on the characteristics of postmenopausal breast cancer in the population of southeastern Europe. This retrospective study explored the clinical, epidemiological, and molecular characteristics of women with postmenopausal breast cancer. MATERIAL AND METHODS: A retrospective cohort study was performed on 721 postmenopausal breast cancer patients selected from the database of our institution. The data collected consisted of age, living environment, location of the breast tumor, stage of the disease, and molecular sub-type. Patient characteristics were collected based on a systematic chart audit from medical records. The data were analyzed using SPSS 20.0 and Pearson analysis. RESULTS: The most frequent age range for breast cancer diagnosis was 51 to 70 years old. Most of the patients (80.7%) came from an urban environment. The vast majority of patients were initially diagnosed in stage II (40.3%) and III (30.3%). The most frequent molecular sub-types were luminal B (39%) and luminal A (35.4%). Almost half of the breast tumors were located in the upper outer quadrant (48.8%). CONCLUSIONS: The results of this study describe the profile of patients in southeastern Europe within our institution diagnosed with postmenopausal breast cancer. In our study, patients were first diagnosed with more advanced stages of breast cancer compared with other European countries.

Rat Animal Model of Pectus Excavatum.

BACKGROUND: pectus excavatum (PE) is the most common congenital deformity of the thoracic wall. Lately, significant achievements have been made in finding new, less invasive treatment methods for PE. However, most of the experimental work was carried out without the help of an animal model. In this report we describe a method to create an animal model for PE in Sprague-Dawley rats. METHODS: We selected 15 Sprague-Dawley rat pups and divided them into two groups: 10 for the experimental group (EG) and 5 for the control group (CG). We surgically resected the last four pairs of costal cartilages in rats from the EG. The animals were assessed by CT-scan prior to surgery and weekly for four consecutive weeks. After four weeks, the animals were euthanized and the thoracic cage was dissected from the surrounding tissue. RESULTS: On the first postoperative CT, seven days after surgery, we observed a marked depression of the lower sternum in all animals from the EG. This deformity was present at every CT-scan after surgery and at the post-euthanasia assessment. CONCLUSIONS: By decreasing the structural strength of the lower costal cartilages, we produced a PE animal model in Sprague-Dawley rats.

Chronic Hindlimb Ischemia Assessment; Quantitative Evaluation Using Laser Doppler in a Rodent Model of Surgically Induced Peripheral Arterial Occlusion.

Therapeutic neoangiogenesis (TNA) holds promise as a treatment for peripheral arterial disease. Nevertheless, proper tools for in vivo pre-clinical investigation of different TNA approaches and their effects are still lacking. Here we describe a chronic ischemic hindlimb model in rats using laser Doppler quantitative evaluation of tissue perfusion. Male Wistar rats (n = 20), aged between 6-8 months, with an average weight of 287 ± 26.74 g, were used. Animals were divided into two experimental groups: group A (n = 17; hindlimb chronic ischemia model) and group B (n = 3; control). Hindlimb ischemia was induced by concomitant ligation of the right femoral and popliteal artery. Evaluation of tissue perfusion was quantified in perfusion units (PU) on a scale from 0 to 500 (500 PU = maximal detectable perfusion) by laser Doppler analysis at day 0, day 15 and day 30 after induction of ischemia. Induction of chronic ischemia in the rat hindlimb by concomitant ligation of the femoral and popliteal artery can be readily obtained but requires basic microsurgical skills. Laser Doppler analysis has shown unaltered ischemia levels throughout the study (129,17 PU ± 3.13 day 0 vs. 130,33 PU day 30 ± 3,27, p = not significant (n.s.)). We demonstrate a simple and reproducible model of chronic hindlimb ischemia in rats, with stable tissue perfusion levels that are accurately quantified using laser Doppler technology. Hence, this model can represent a valid tool for further studies involving therapeutic neoangiogenesis.

Aspects of renal function in patients with colorectal cancer in a gastroenterology clinic of a county hospital in Western Romania.

Colorectal cancer represents the third cause of cancer. Since its detection in due time is important resolution, appropriate monitoring is mandatory. The present study deals with the relationship between colorectal cancer and renal function, as well as other associated risk factors. Chronic kidney disease (CKD) represents a risk factor of cancer, both in non-dialysed patients and especially in dialysed patients and in patients with renal transplant. It can get aggravated with cancer in general and particularly with colorectal cancer, partly related to the toxins that cannot be appropriately eliminated because of renal functional disturbances. At the same time, immunosuppressive therapy used for treating glomerular or secondary nephropathies represents an important risk factor of cancer. Some patients with colorectal cancer were found to present also impaired renal function, a fact whose significance is still little known. The object of the present paper is an analysis of the case records of a clinic of gastroenterology on the relationship between colorectal cancer and renal functional impairment. We found in the patients with colorectal cancer under study a glomerular filtration rate (GFR calculated with the EPI formula) of < 60 ml/min/1.73m2 in 31/180 patients, respectively 17.22% of the cases, a value that is similar to that in specialised literature. We also analysed associated risk factors that could be related to renal function impairment in these patients: age, gender, anaemia, diabetes mellitus and hypertension. These could represent, together with the colorectal cancer of the investigated patients, risk factors affecting on the one hand renal function, and on the other hand, potentially increasing the risk of cancer. Correction of these risk factors would have beneficial effects on patients. The relationship between renal functional impairment, respectively CKD, and colorectal cancer is to be regarded from the point of view of complex reciprocity: the impairment of the renal function is a factor of risk of colorectal cancer and colorectal cancer can influence renal function of these patients. This report of reciprocity based on important pathogenic mechanisms also interrelates with factors of risk consecutive to both renal function impairment and colorectal cancer.