Showing papers by "Clinical Emergency Hospital Bucharest published in 2021"

PI3K/AKT/mTOR signalling pathway involvement in renal cell carcinoma pathogenesis (Review).

Abstract: Renal cell carcinoma (RCC) accounts for over 90% of all renal malignancies, and mainly affects the male population. Obesity and smoking are involved in the pathogenesis of several systemic cancers including RCC. The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway regulates cell growth, differentiation, migration, survival, angiogenesis, and metabolism. Growth factors, hormones, cytokine and many extracellular cues activate PI3K/AKT/mTOR. Dysregulation of this molecular pathway is frequently reported in human cancers including RCC and is associated with aggressive development and poor survival rate. mTOR is the master regulator of cell metabolism and growth, and is activated in many pathological processes such as tumour formation, insulin resistance and angiogenesis. mTOR inhibitors are used at present as drug therapy for RCC to inhibit cell proliferation, growth, survival, and the cell cycle. Temsirolimus and everolimus are two mTOR inhibitors that are currently used for the treatment of RCC. Drugs targeting the PI3K/AKT/mTOR signalling pathway may be one of the best therapeutic options for RCC.

Cardiovascular Stents: A Review of Past, Current, and Emerging Devices.

Abstract: One of the leading causes of morbidity and mortality worldwide is coronary artery disease, a condition characterized by the narrowing of the artery due to plaque deposits. The standard of care for treating this disease is the introduction of a stent at the lesion site. This life-saving tubular device ensures vessel support, keeping the blood-flow path open so that the cardiac muscle receives its vital nutrients and oxygen supply. Several generations of stents have been iteratively developed towards improving patient outcomes and diminishing adverse side effects following the implanting procedure. Moving from bare-metal stents to drug-eluting stents, and recently reaching bioresorbable stents, this research field is under continuous development. To keep up with how stent technology has advanced in the past few decades, this paper reviews the evolution of these devices, focusing on how they can be further optimized towards creating an ideal vascular scaffold.

Editing and Chemical Modifications on Non-Coding RNAs in Cancer: A New Tale with Clinical Significance.

Abstract: Currently, for seemingly every type of cancer, dysregulated levels of non-coding RNAs (ncRNAs) are reported and non-coding transcripts are expected to be the next class of diagnostic and therapeutic tools in oncology. Recently, alterations to the ncRNAs transcriptome have emerged as a novel hallmark of cancer. Historically, ncRNAs were characterized mainly as regulators and little attention was paid to the mechanisms that regulate them. The role of modifications, which can control the function of ncRNAs post-transcriptionally, only recently began to emerge. Typically, these modifications can be divided into reversible (i.e., chemical modifications: m5C, hm5C, m6A, m1A, and pseudouridine) and non-reversible (i.e., editing: ADAR dependent, APOBEC dependent and ADAR/APOBEC independent). The first research papers showed that levels of these modifications are altered in cancer and can be part of the tumorigenic process. Hence, the aim of this review paper is to describe the most common regulatory modifications (editing and chemical modifications) of the traditionally considered "non-functional" ncRNAs (i.e., microRNAs, long non-coding RNAs and circular RNAs) in the context of malignant disease. We consider that only by understanding this extra regulatory layer is it possible to translate the knowledge about ncRNAs and their modifications into clinical practice.

Novel chitosan and bacterial cellulose biocomposites tailored with polymeric nanoparticles for modern wound dressing development.

Abstract: Dressing biomaterials play a key role in wound management keeping a moisture medium and protecting against external factors. Natural and synthetic materials could be used as dressings where chitosan and bacterial cellulose is one of the most important solutions. These biopolymers have been used for wound dressing based on their non-toxic, biodegradable, and biocompatible features. In this study, biocomposites based on bacterial cellulose and chitosan membranes tailored with antimicrobial loaded poly(N-isopropylacrylamide)/polyvinyl alcohol nanoparticles were prepared. Core-shell polymeric nanoparticles, bacterial cellulose/chitosan membranes, and biocomposites were independently loaded with silver sulfadiazine, a well-known sulfonamide antibacterial agent used in the therapy of mild-to-moderate infections for sensitive organisms. The chemistry, structure, morphology, and size distribution were investigated by Fourier transformed infrared spectroscopy (FTIR-ATR), RAMAN spectroscopy, Scanning electron (SEM) and Transmission electron microscopy (TEM), and Dynamic light scattering (DLS). In vitro release behaviors of silver sulfadiazine from polymeric nanoparticles and biocomposites were investigated. The biological investigations revealed good biocompatibility of both the nanoparticles and the biocomposites in terms of human dermal fibroblasts viability and proliferation potential. Finally, the drug-loaded polymeric biomaterials showed promising characteristics, proving their high potential as an alternative support to develop a biocompatible and antibacterial wound dressing.

Significance of Neutrophil to Lymphocyte Ratio (NLR) and Platelet Lymphocyte Ratio (PLR) in Diabetic Foot Ulcer and Potential New Therapeutic Targets.

Abstract: Diabetic foot ulcer (DFU) is a well-known complication of diabetes and a significant burden on the national health systems. The neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio are inexpensive and easily accessible biomarkers that have proved to be useful in several inflammatory, infectious and cardiovascular diseases. We carried out a comprehensive review examining the association of NLR and PLR with the onset and progression of DFU. PLR and NLR were significantly increased in patients with DFU, compared with a control group of T2DM patients without DFU, and correlate well with DFU severity, evaluated by Wagner and IWGDF grading scales. In patients with diabetic foot infections (DFI), elevated NLR and PLR were correlated with osteomyelitis, increased risk of amputation, and septic complications. The significance of the elevated value of these biomarkers in DFU is related to chronic hyperglycemia and low-grade systemic inflammation, atherosclerotic and vascular complications, and also the associated septic factor. Serial, dynamic follow-up can provide useful information in planning and monitoring DFU treatment, as well as in risk stratification of these vulnerable patients. Further randomized studies are needed to set the cut-off values with clinical significance.

Impact of adipose tissue in chronic kidney disease development (Review).

Abstract: Obesity is a worldwide pandemic health issue. Obesity is associated with the pathogenesis of type 2 diabetes, hypertension, dyslipidemia, cardiovascular diseases, cancer, and kidney diseases. This systemic disease can affect the kidneys by two mechanisms: Indirectly through diabetes mellitus (DM) and hypertension and directly through adipokines secreted by adipose tissue. Obesity is a risk factor for chronic kidney disease (CKD), which is associated with an increased risk of morbidity and mortality among the adult population. Increased visceral adipose tissue leads to renal glomerular hyperfiltration and hyperperfusion, which may lead to glomerular hypertrophy, proteinuria, and CKD development. Adipokines are hormones produced by fat tissue. They are involved in energy homeostasis, sugar and fat metabolism, reproduction, immunity, and thermogenesis control. Hormones and cytokines secreted by adipose tissue contribute to the development and progression of CKD. Decreased serum or urinary adiponectin levels are specific in diabetic and non-diabetic CKD patients, while leptin presents increased levels, and both are associated with the development of glomerulopathy. Excessive adipose tissue is associated with inflammation, oxidative stress (OS), insulin resistance and activation of the renin angiotensin-aldosterone system (RAAS). Therefore, adipose tissue dysfunction plays an important role in the development of CKD.

Impact of Increased Oxidative Stress on Cardiovascular Diseases in Women With Polycystic Ovary Syndrome

Abstract: Polycystic ovary syndrome (PCOS) is a complex disorder that affects around 5% to 10% of women of childbearing age worldwide, making it the most common source of anovulatory infertility. PCOS is defined by increased levels of androgens, abnormal ovulation, irregular menstrual cycles, and polycystic ovarian morphology in one or both ovaries. Women suffering from this condition have also been shown to frequently associate certain cardiovascular comorbidities, including obesity, hypertension, atherosclerosis, and vascular disease. These factors gradually lead to endothelial dysfunction and coronary artery calcification, thus posing an increased risk for adverse cardiac events. Traditional markers such as C-reactive protein (CRP) and homocysteine, along with more novel ones, specifically microRNAs (miRNAs), can accurately signal the risk of cardiovascular disease (CVD) in PCOS women. Furthermore, studies have also reported that increased oxidative stress (OS) coupled with poor antioxidant status significantly add to the increased cardiovascular risk among these patients. OS additionally contributes to the modified ovarian steroidogenesis, consequently leading to hyperandrogenism and infertility. The present review is therefore aimed not only at bringing together the most significant information regarding the role of oxidative stress in promoting CVD among PCOS patients, but also at highlighting the need for determining the efficiency of antioxidant therapy in these patients.

In Vitro Interaction of Doxorubicin-Loaded Silk Sericin Nanocarriers with MCF-7 Breast Cancer Cells Leads to DNA Damage.

Abstract: In this paper, Bombyx mori silk sericin nanocarriers with a very low size range were obtained by nanoprecipitation. Sericin nanoparticles were loaded with doxorubicin, and they were considered a promising tool for breast cancer therapy. The chemistry, structure, morphology, and size distribution of nanocarriers were investigated by Fourier transformed infrared spectroscopy (FTIR-ATR), scanning electron microscopy (SEM) and transmission electron microscopy (TEM), and dynamic light scattering (DLS). Morphological investigation and DLS showed the formation of sericin nanoparticles in the 25-40 nm range. FTIR chemical characterization showed specific interactions of protein-doxorubicin-enzymes with a high influence on the drug delivery process and release behavior. The biological investigation via breast cancer cell line revealed a high activity of nanocarriers in cancer cells by inducing significant DNA damage.

Myelomeningocele Surgery over the 10 Years Following the MOMS Trial: A Systematic Review of Outcomes in Prenatal versus Postnatal Surgical Repair.

Abstract: Background and Objectives: Myelomeningocele is the most severe form of spina bifida, a congenital neural tube defect arising from an incomplete neural tube closure during early development with damage worsening with advancing gestational age. The Management of Myelomeningocele Study (MOMS) Trial proved that surgery performed before 26 weeks of gestation significantly improved the prognosis, significantly changing treatment paradigms. This article aims to provide a review of the changes and updates in spina bifida repair over the 10-year period following the MOMS Trial. Material and methods: We performed a systematic review in the PubMed and Cochrane databases as well as a hand-search of high-impact journals using the reference list of all identified articles, searching for randomized controlled trials and observational studies. Results: We identified 27 articles published between 2011 and 2021 that fulfilled the inclusion criteria and review them in the present study. Conclusions: With growing experience and with the improvement of prenatal open and fetoscopic techniques, the outcome of SB-associated conditions could be improved and the risks to both the mother and the fetus reduced. A continuous follow-up of the treated infants and further randomized trials are essential to study the complications and advantages or disadvantages of any given treatment strategy.

Association between Liver Cirrhosis and Diabetes Mellitus: A Review on Hepatic Outcomes.

Abstract: Background: Liver cirrhosis (LC) is largely associated with diabetes mellitus (DM). More than 80% of patients with LC manifest glucose intolerance and about 30% have type 2 DM. A particular and yet unrecognized entity is hepatogenous diabetes (HD), defined as impaired glucose regulation caused by altered liver function following LC. Numerous studies have shown that DM could negatively influence liver-related outcomes. Aim: We aimed to investigate whether patients with LC and DM are at higher risk for hepatic encephalopathy (HE), variceal hemorrhage (VH), infections and hepatocellular carcinoma (HCC). The impact of DM on liver transplant (LT) outcomes was also addressed. Methods: Literature search was performed in PubMed, Ovid, and Elsevier databases. Population-based observational studies reporting liver outcomes in patients with LC were included. Results: Diabetics are at higher risk for HE, including post-transjugular intrahepatic portosystemic shunt HE. DM also increases the risk of VH and contributes to elevated portal pressure and variceal re-bleeding, while uncontrolled DM is associated with increased risk of bacterial infections. DM also increases the risk of HCC and contributes to adverse LT outcomes. Conclusions: Patients with DM and LC may benefit from close follow-up in order to reduce readmissions and mortality. Due to the heterogeneity of available research, prospective multicenter clinical trials are needed to further validate these findings.

Remote Ischemic Conditioning May Improve Disability and Cognition After Acute Ischemic Stroke: A Pilot Randomized Clinical Trial.

Abstract: Background and Aim: Remote ischemic conditioning is a procedure purported to reduce the ischemic injury of an organ. This study aimed to explore the efficiency and safety of remote ischemic conditioning in patients with acute ischemic stroke. We hypothesized that remote ischemic conditioning administered from the first day of hospital admission would improve the infarct volume and clinical outcome at 180 days. Material and Methods: We performed a unicentric double-blind randomized controlled trial. We included all patients consecutively admitted to an Emergency Neurology Department with acute ischemic stroke, ineligible for reperfusion treatment, up to 24 hours from onset. All subjects were assigned to receive secondary stroke prevention treatment along with remote ischemic conditioning on the non-paretic upper limb during the first 5 days of hospitalization, twice daily - a blood pressure cuff placed around the arm was inflated to 20 mmHg above the systolic blood pressure (up to 180 mmHg) in the experimental group and 30 mmHg in the sham group. The primary outcome was the difference in infarct volume (measured on brain CT scan) at 180 days compared to baseline, whereas the secondary outcomes included differences in clinical scores (NIHSS, mRS, IADL, ADL) and cognitive/mood changes (MoCA, PHQ-9) at 180 days compared to baseline. Results: We enrolled 40 patients; the mean age was 65 years and 60% were men. Subjects in the interventional group had slightly better recovery in terms of disability, as demonstrated by the differences in disability scores between admission and 6 months (e.g., the median difference score for Barthel was -10 in the sham group and -17.5 in the interventional group, for ADL -2 in the sham group and -2.5 in the interventional group), as well as cognitive performance (the median difference score for MoCA was -2 in the sham group and -3 in the interventional group), but none of these differences reached statistical significance. The severity of symptoms (median difference score for NIHSS = 5 for both groups) and depression rate (median difference score for PHQ-9 = 0 for both groups) were similar in the two groups. The median difference between baseline infarct volume and final infarct volume at 6 months was slightly larger in the sham group compared to the interventional group (p = 0.4), probably due to an initial larger infarct volume in the former. Conclusion: Our results suggest that remote ischemic conditioning might improve disability and cognition. The difference between baseline infarct volume and final infarct volume at 180 days was slightly larger in the sham group.

A spotlight on underlying the mechanism of AMPK in diabetes complications.

Abstract: Type 2 diabetes (T2D) is one of the centenarian metabolic disorders and is considered as a stellar and leading health issue worldwide. According to the International Diabetes Federation (IDF) Diabetes Atlas and National Diabetes Statistics, the number of diabetic patients will increase at an exponential rate from 463 to 700 million by the year 2045. Thus, there is a great need for therapies targeting functions that can help in maintaining the homeostasis of glucose levels and improving insulin sensitivity. 5′ adenosine monophosphate-activated protein kinase (AMPK) activation, by various direct and indirect factors, might help to overcome the hurdles (like insulin resistance) associated with the conventional approach. A thorough review and analysis was conducted using various database including MEDLINE and EMBASE databases, with Google scholar using various keywords. This extensive review concluded that various drugs (plant-based, synthetic indirect/direct activators) are available, showing tremendous potential in maintaining the homeostasis of glucose and lipid metabolism, without causing insulin resistance, and improving insulin sensitivity. Moreover, these drugs have an effect against diabetes and are therapeutically beneficial in the treatment of diabetes-associated complications (neuropathy and nephropathy) via mechanism involving inhibition of nuclear translocation of SMAD4 (SMAD family member) expression and association with peripheral nociceptive neurons mediated by AMPK. From the available information, it may be concluded that various indirect/direct activators show tremendous potential in maintaining the homeostasis of glucose and lipid metabolism, without resulting in insulin resistance, and may improve insulin sensitivity, as well. Therefore, in a nut shell, it may be concluded that the regulation of APMK functions by various direct/indirect activators may bring promising results. These activators may emerge as a novel therapy in diabetes and its associated complications.

Management strategies and clinical follow-up of pregnant women with intracranial meningioma.

Abstract: Meningiomas are common primary tumors of the central nervous system. The incidence at the age of fertility is low, although there are some hormonal mechanisms involved. Growth in size was observed during the luteal phase of the menstrual cycle, which could lead to developing new symptoms during pregnancy or worsening of the already existing ones. Visual impairment is the chief complaint, followed by headache, nausea, vomiting, and seizures. Diagnosis is based on neurological examination, ophthalmoscopy, imaging techniques like gadolinium-enhanced magnetic resonance imaging (MRI), and contrast-enhanced computed tomography (CT) scans, bearing in mind the patient's irradiation and prejudice on the fetus together with the histopathological examination. The objective of the review is to determine the influence of meningioma on pregnancy and vice-versa and provide a strategy of follow-up for maternal-fetal specialists and not only. We performed a systematic review by searching relevant information in PubMed and Wiley databases using keywords as meningioma, pregnancy, progesterone receptors. The results showed that besides a similar incidence of meningioma in pregnant and non-pregnant women, symptoms might flare during pregnancy due to water retention, engorgement of vessels, and the presence of sex hormone receptors on tumor cells. Meningioma may impact the route of pregnancy with adverse effects on the fetus. Thus, fetal monitoring by biophysical profile and cardiotocography (CTG) is needed. The preferred treatment option is surgery, but gestational age and the woman's status must be taken into consideration.

Single-use ureteroscopes in ectopic pelvic kidney stones.

Abstract: We analyzed the results of single-use flexible ureteroscopy (su-fURS) with the holmium laser in treating renal stones associated with ectopic pelvic kidney (EPK). The study retrospectively analyzed data of 11 patients diagnosed with EPK and stone disease who underwent su-fURS between May 2017 and November 2019. The analyzed surgical data included the mean operation time, stone-free and complication rates, as well as hospitalization period. Disposable digital flexible ureteroscopes were exclusively used. The mean age was 55, with a 1.2:1 male to female ratio. The mean stone burden was 30±9 mm (ranging from 17 to 49 mm). The mean calculi digitized surface area (DSA) was 299±56 mm2 (ranging from 170 to 597 mm2). A ureteral access sheath was used in all 11 patients, and holmium laser lithotripsy was performed (dusting mode parameters: low energy - 0.5J, high frequency - 50 Hz, long pulse; pop-corn mode: high energy >1 J, medium frequency- 10-50 Hz, long pulse; fragmenting mode: high energy >1 J, low frequency <10 Hz, short pulse). The average operative time was 78±19 minutes (ranging from 68 to 144 minutes). The stone-free status (residual fragments <3 mm) after one session was 60.1%, 84.1% after the second session, and 94.4% after the third session. The hospitalization period was 29 hours (ranging from 17 to 39 hours). The overall complications rate (according to the Clavien-Dindo system) was 19.7%. Therefore, su-fURS represents an effective therapeutic approach characterized by a remarkably high stone-free rate and few complications in EPK-associated calculi.

Dysregulation of miRNAs Targeting the IGF-1R Pathway in Pancreatic Ductal Adenocarcinoma

Abstract: Background: Pancreatic ductal adenocarcinoma (PDAC), the most prevalent neoplastic lethal pancreatic disease, has a poor prognosis and an increasing incidence. The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is considered to be a contributing factor to the progression, metastasis, and therapy resistance of PDAC. Currently available treatment options for PDAC are limited, but microRNAs (miRNAs) may represent a new therapeutic strategy for targeting genes involved in the IGF-1R signaling pathway. Method: We investigated the expression levels of 21 miRNAs involved in the IGF-1R signaling pathway in pancreatic tissue from 38 patients with PDAC and 11 controls (five patients with chronic pancreatitis and six patients with normal pancreatic tissue). Results: We found 19 differentially expressed miRNAs between the PDAC cases and the controls. In particular, miR-100-5p, miR-145-5p, miR-29c-3p, miR-9-5p, and miR-195-5p were exclusively downregulated in PDAC tissue but not in chronic pancreatitis or normal pancreatic tissues; both control types presented similar levels. We also identified miR-29a-3p, miR-29b-3p, and miR-7-5p as downregulated miRNAs in PDAC tissues as compared with normal tissues but not with pancreatitis tissues. Conclusions: We identified a panel of miRNAs that could represent putative therapeutic targets for the development of new miRNA-based therapies for PDAC.

Romanian National premiere with the new Thulium SuperPulsed Laser in the endourological treatment of urolithiasis.

Abstract: In this paper, we aimed to verify the efficiency and functionality of the new Soltive Thulium Fiber Laser (TFL) in the treatment of urinary stones. The Soltive Laser System was used in 17 urolithiasis cases: 10 renal, 5 ureteral, and 2 bladder stone patients. The average stone size was 13.1 mm (ranging between 11-29 mm) for the kidney, 8 mm (ranging between 6-12 mm) for the ureter, and 31 mm (ranging between 27-34 mm) for the bladder. Only single calculi patients were included in the study. We used 100 and 150 μm core-diameters fibers (CDF). Three settings were applied: 0.15 J/100 Hz for "fine dusting", 0.5 J/30 Hz for "dusting" and 1 J/15 Hz for the fragmentation mode. The mean operative time was 34 minutes for renal, 21 minutes for ureteral, and 39 minutes for bladder stones. The visibility was optimal in all cases. The stone-free rate at 1 month after treatment was 95% for renal calculi and 100% for ureteral and bladder stones. Very fine dust made of stone fragments smaller than 1 mm in size that passed spontaneously through the access sheath was observed, especially subsequent to the "fine dusting" mode. The complication rate was very low: 1 patient was classified as Clavien grade 1 and 1 patient as Clavien grade 2, and this was the case for renal stones only. No urinary tract infections were observed. The new Soltive TFL appears to be a remarkably promising tool in the therapeutic approach of urolithiasis. Lithotripsy was achieved up to the level of extremely small stone fragments with improved efficiency while also optimizing the operative time.

Ratio between Right Ventricular Longitudinal Strain and Pulmonary Arterial Systolic Pressure: Novel Prognostic Parameter in Patients Undergoing Cardiac Resynchronization Therapy.

Abstract: Background: We aimed to evaluate whether right ventricle (RV) longitudinal strain indexed to pulmonary arterial systolic pressure (PASP) has prognostic significance in patients undergoing cardiac resynchronization therapy (CRT). Methods: Patients undergoing CRT were prospectively included. The primary endpoint was adverse cardiovascular events (death and HF-related hospitalizations). RV global longitudinal strain (RVGLS) and RV free wall strain (RVfwS) were measured by speckle tracking and indexed to echocardiographic estimated PASP. Results: A total of 54 patients (64.0 ± 13.8 years; 58% male) were included. After 33 ± 12.9 months, the primary endpoint occurred in 18 patients. Baseline RVGLS/PASP and RVfwS/PASP showed good discriminative ability for response to CRT (AUC = 0.88, 95% CI (0.74–1) and AUC = 0.87, 95% CI (0.77–1)). RVGLS/PASP and RVfwS/PASP were significantly associated with high risk of events at univariate analysis (HR 0.039, 95% CI (0.001–0.8) p < 0.05, respectively HR = 0.049, 95% CI (0.0033–0.72), p < 0.05). Upon multivariate Cox regression analysis, RVGLS/PASP and RVfwS/PASP remained associated with high risk of events (HR 0.018, 95% CI (0.0005–0.64), p = 0.02 and HR 0.015, 95% CI (0.0004–0.524), p = 0.01) after correction for gender, etiology, QRS duration and morphology. Conclusions: Indexing RV longitudinal strain (global and free wall) by PASP provides a parameter, which independently identifies patients with high risk of cardiovascular events and predicts non-response to CRT.

Use of platelet-rich plasma in the treatment of infertility in poor responders in assisted human reproduction procedures.

Abstract: Couple infertility is a pathology with an absolute number of cases growing markedly over the last decade in connection mainly with the increased age of couples wishing to conceive. Platelet-rich plasma (PRP) is an alternative treatment used for several years for experimental purposes. Yet, this method is not yet defined as a standard therapeutic option in the infertility protocol for poor responders in assisted human reproduction procedures. Thus, the present study is a retrospective study conducted between February 2019 and February 2020 to evaluate the effect of ovarian PRP injection in patients with a poor ovarian response (POR) to ovarian stimulation. Women (n=20; age 31-44 years) diagnosed with POR based on the European Society of Human Reproduction and Embryology criteria underwent ovarian injection with autologous PRP injection. Markers of ovarian reserve before, during the following two menstrual cycles, and at six months after treatment were followed as well as stimulation and fertilisation parameters before and post-treatment. PRP treatment resulted in increased antral follicle count and serum anti-Mullerian hormone, while levels of serum follicle-stimulating hormone and luteinising hormone were decreased. These changes were more pronounced during the 2nd menstrual cycle following treatment. By six months following the injection, their values return to pre-treatment levels and any small differences were not considered statistically significant. The average dose of gonadotropin used and duration remained statistically unchanged, but a significant increase in estradiol achieved by the day of the human chorionic gonadotropin trigger day was achieved. The cancellation rate decreased following PRP treatment while the number of collected oocytes, number of oocytes in metaphase II rose. The number of embryos (of A and B quality) resulting also increased but fell short of the significance level set (α=0.073). Following the PRP injection, two singleton pregnancies were achieved, resulting in live births at term without complications during pregnancy. Another pregnancy was achieved spontaneously 45 months following the PRP and a failed assisted human reproduction procedure. Although the group included a small number of women, the results indicate the potential benefits of an ovarian autologous PRP injection in women with POR. Positive results appear to be short-term for 2-6 months after the procedure.

Investigating Caesarean Section Practice among Teenage Romanian Mothers Using Modified Robson Ten Group Classification System.

Abstract: The Robson ten-group classification system is a recognized effective method of assessing caesarean rate. It is based on dividing patients into ten mutually exclusive groups, focusing on six maternal and newborn variables (parity, gestational age, plurality, foetal presentation, previous caesarean, and mode of labour onset). The aim of our analysis was twofold: first, to present the implementation of Robson classification in a pregnant teenage population; and second, to identify the indications for CS in the adolescent population. This study was designed as a one-year prospective analysis and considered all women younger than 20 years of age who delivered in a tertiary care hospital. Before discharge, women who had caesarean delivery responded to a questionnaire regarding their education, prenatal surveillance, and obstetrical history. Caesarean sections accounted for 47.01% of all births. A proportion of 24.57% of the participants had at least one previous caesarean section. Group 10 (all women with a single cephalic preterm pregnancy) was second most often identified among women in middle adolescence (14.03%); 32.20% of the participants in late adolescence were in group 5 (multiparas with a scarred uterus, single cephalic term pregnancy). Differences between the two age groups were not statistically different (p = 0.96). Abnormal cardiotocographic findings (38.23%), the arrest of descent (19.11%) and arrest of dilation (19.11%), were the most frequent indications for caesareans in Robson group 1. Neonates from mothers in Robson groups 8 (women with a multiple pregnancy) and 7 (multiparas single breech pregnancy) had the most unfavourable outcomes regarding gestational age at delivery and admission to the intensive care unit. We concluded that future focus on obstetrical management is mandatory in Robson groups 7 and 8. Adolescents in Robson group 1 (nulliparas, single cephalic term pregnancy, spontaneous labour) are the primary beneficiaries of strategies to reduce caesarean sections rates.

High-normal blood pressure and related cardiovascular risk factors prevalence in the Romanian adult population: insights from the SEPHAR III study.

Abstract: High normal blood pressure (HNBP) is associated with an increased risk of incident high blood pressure (HBP) and of cardiovascular diseases (CVD). To estimate the prevalence of HNBP and related cardiovascular risk factors, a representative sample of 1970 Romanian adults was enrolled in SEPHAR III survey (Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania). All were evaluated for blood pressure values and by a 71-item questionnaire, anthropometric measurements, together with extensive evaluation for target organ damage, blood, and urine sample collection. Prevalence of HNBP was 11% [45.1% had HBP, 43.9% normal BP (NBP)]. HNBP individuals were older (51.14 ± 17.13 years) than subjects with NBP (40.5 ± 15.96 years) but younger than those with HBP (55.79 ± 15.68 years), p < 0.0001 (95% CI 18-85, respectively 18-91). Values of weight, waist circumference, body mass index, total and LDL cholesterol, triglycerides, fasting blood glucose, glycosylated hemoglobin (HbA1c), uric acid, serum creatinine, glomerular filtration rate estimate by CKD-EPI equation, urinary albumin to creatinine ratio, intimae-media thickness, arterial stiffness measurements and diastolic dysfunction, indexed left ventricular mass, interventricular septum and posterior left ventricle wall thickness, left atrial volume, and LA dilatation were significantly higher in HNBP subjects than in NBP. Our study showed that individuals with HNBP represent ~11% and most of them had an elevated total cardiovascular risk. It is essential to educate the public and health care providers to be aware of these individuals and of steps that should be taken to treat modifiable cardiovascular risk factors.

Management of acute intradialytic cardiovascular complications: Updated overview (Review).

Abstract: An increasing number of patients require renal replacement therapy through dialysis and renal transplantation. Chronic kidney disease (CKD) affects a large percentage of the world's population and has evolved into a major public health concern. Diabetes mellitus, high blood pressure and a family history of kidney failure are all major risk factors for CKD. Patients in advanced stages of CKD have varying degrees of cardiovascular damage. Comorbidities of these patients, include, on the one hand, hypertension, hyperlipidemia, hyperglycemia, hyperuricemia and, on the other hand, the presence of mineral-bone disorders associated with CKD and chronic inflammation, which contribute to cardiovascular involvement. Acute complications occur quite frequently during dialysis. Among these, the most important are cardiovascular complications, which influence the morbidity and mortality rates of this group of patients. Chronic hemodialysis patients manifest acute cardiovascular complications such as intradialytic hypotension, intradialytic hypertension, arrhythmias, acute coronary syndromes and sudden death. Thus, proper management is extremely important.

Age in the Time of COVID-19: An Ethical Analysis

Abstract: Despite using a myriad of methods to combat the spread of COVID-19, the healthcare systems (especially the intensive care units) have been overwhelmed, showing an outpaced capacity of available beds and ventilators. Choosing the right criteria to allocate the scarce ICU seems very challenging, being necessary a rapid, uncomplicated and universally accepted tool for patients' triage regarding access to lifesaving resources; one such criterion, which generates intense debates, is age. Under certain circumstances, it might seem appropriate to choose to treat a young over an old patient. The main advantage of this approach is the potential for long-term survival, implying an equal right to reach an advanced age. Many authors have given moral reasons to support it, mainly based on utilitarian ethics or on distributive justice. However, there are numerous counterarguments to this approach, which we will summarize in this article. We will show that age should never be used as a unique criterion for withholding/not initiating life-saving procedures, even in pandemics or cases in which healthcare resources are extremely scarce. This approach is based on fundamental Codes of Ethics, such as the WMA Code of Ethics or the Oath of Hippocrates and all physicians treating patients should obey them.

Superior Sinus Venosus Atrial Septal Defect with Partial Anomalous Pulmonary Venous Drainage-Minimally Invasive Approach-Case Report.

Abstract: The atrial septal defect is, after bicuspid aortic valve disease, the most common congenital cardiac disease present in the adult population. The most common atrial septal defects are the ostium secundum type (75-80%), followed by the ostium primum type (15%). The sinus venosus atrial septal defects (SV-ASD), defined as a communication in the posterior part of the interatrial septum, account for about 5 to 10% of atrial septal defects. Approximately 90% of SV-ASDs are associated with partial anomalous pulmonary venous drainage (PAPVD). The minimally invasive approach has gained ground in the treatment of ASDs, especially those of the ostium secundum type. The sinus venosus type is a relatively uncommon form of ASD, which, when associated with a PAPVD, is considered a complex cardiac malformation, and is usually treated in a classical manner, through median sternotomy. We describe the case of a 45-year-old woman diagnosed in adolescence with SV-ASD with PAPVD, who successfully underwent minimally invasive repair with fresh autologous pericardial patch reconstruction through an anterolateral mini-thoracotomy incision. The patient presented with shortness of breath and fatigue after heavy exertions, episodes of paroxysmal nocturnal dyspnea, palpitations during effort and at rest, and had a history of syncope dating from 17 years previously. Echocardiography revealed an SV-ASD with PAPVD in the right atrium and the intraoperative examination discovered that both right pulmonary veins were draining into the superior vena cava.

The "no-touch" technique in the flexible ureteroscopic approach of renal stones.

Abstract: Large meta-analyses demonstrated that ureteral access sheaths (UAS) have specific complications during and after flexible ureteroscopy (fURS). The present study focused on the technical aspects, advantages, drawbacks, and limitations of the latest "no-touch" technique (NTT) in the flexible ureteroscopic therapeutic approach of renal stones. A total of 288 patients with a single pyelocaliceal stone (largest diameter between 11 and 29 mm) underwent fURS: 144 using the 12/14 Fr UAS (group 1) and 144 without UAS (group 2). For NTT, we used four types of ureteroscopes: Olympus URF-V2 (8.5 Fr) - 33 cases, Storz Flex X2 (8.4 Fr) - 60 cases, single-use PUSEN PU 3022 (9.5 Fr) - 37 cases, and single-use PUSEN - PU 3033A (7.5 Fr) - 14 cases. For group 1, we used the Olympus URF-V2 ureteroscope in 44 cases, the Storz Flex X2 in 58 cases, and the single-use PUSEN PU 3022 in 42 cases. We compared the operative time, hospitalization periods, and complications. Successful access sheath insertion was noted in 83.3% of cases from group 1, and successful ureteroscope insertion was noted in 90.9% of cases from group 2. The average operative time was slightly higher in group 1 vs. group 2 (47 vs. 39 min). Stone-free rates (SFRs) were overall lower in group 2 (76.3% vs. 86.8%) at 1 month. At 3 months, we did not find a significant difference between these two groups. Superficial mucosal ureteral wall lesions were found in 38.8% of patients from group 1 and 4.1% from group 2. Hospitalization periods were longer in group 1 vs. group 2 (21 vs. 29 hours, respectively). The single-use 7.5 Fr ureteroscope should receive a special mention: the insertion was simple, we did not encounter any mucosal ureteral wall lesions, and all patients were discharged on the same day. Despite the clear advantages of routine UAS usage, there are many adverse events for the patient. Larger diameter sheaths involve a greater risk of ureteral wall injury. NTT seems to improve peri- and postoperative safety while preserving therapeutic efficiency. The new 7.5 Fr ureteroscopes appear to optimize surgical efficiency and diminish complications in the flexible ureteroscopic treatment of renal stones.

Diagnosis of Cardiac Abnormalities in Muscular Dystrophies.

Abstract: Muscular disorders are mainly characterized by progressive skeletal muscle weakness. There are several aspects that can be monitored, which are used to differentiate between the types of muscular disorders, ranging from the targeted muscle up to the mutated gene. An aspect that holds critical importance when managing muscular dystrophies is that most of them exhibit cardiac abnormalities. Therefore, cardiac imaging is an essential part of muscular disorder monitoring and management. In the first section of the review, several cardiac abnormalities are introduced; afterward, different muscular dystrophies’ pathogenesis is presented. Not all muscular dystrophies necessarily present cardiac involvement; however, the ones that do are linked with the cardiac abnormalities described in the first section. Moreover, studies from the last 3 years on muscular disorders are presented alongside imaging techniques used to determine cardiac abnormalities.

In Vitro Cytotoxic Protective Effect of Alginate-Encapsulated Capsaicin Might Improve Skin Side Effects Associated with the Topical Application of Capsaicin.

Abstract: Chronic neuropathic pain, particularly peripheral pain, is a cause of great concern for diabetic patients. Current treatments include numerous agents such as capsaicinoids, a known deterrent of neuropathic pain despite the inconvenience associated with local side effects. In this context, the current work aims to elucidate the potential mechanisms involved in cytotoxicity by capsaicin and proposes an efficient formulation of capsaicin in alginate microcapsules, which significantly reduces side effects from capsaicin topical administration. For this, human dermal fibroblast cells were treated with alginate-microencapsulated capsaicin extracts and screened for potential cytotoxic effects produced by the treatment. Cell viability and morphology were examined, as well as oxidative stress status and anti-inflammatory potential. Our results show that the alginate encapsulated formulation of capsaicin exerted lower cytotoxic effects on human dermal fibroblasts as measured by cell viability and reactive oxygen species (ROS) production. Furthermore, the expression profiles of inflammatory cytokines were significantly altered by the treatment as compared with the control culture.

The prevalence of SARS-CoV-2 antibodies in triage-negative patients and staff of a fertility setting from lockdown release throughout 2020

Abstract: Study question What is the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in triage-negative patients undergoing ART and fertility care providers after lockdown release and throughout 2020? Summary answer Out of the triage-negative patients whose blood samples were assessed for SARS-CoV-2 antibodies over 6 months, 5.2% yielded positive results with a significantly higher rate in health care workers (HCWs) and a significant month-by-month increase in those with evidence of antibodies. What is known already Patients of reproductive age are more prone to asymptomatic or minimal forms of coronavirus disease 2019 (COVID-19) as compared to older age groups, and the identification of those with active infection and those already exposed (and probably immunized) is important for safety and cost-effective use of testing resources in the fertility setting. Data on the prevalence of SARS-CoV-2 in ART patients are limited and encompass short time frames; current rates are unknown. There is also no consensus on the optimal way of screening triage-negative ART patients in moderate/high-risk areas. Study design size duration A prospective longitudinal unicentric study on triage negative ART patients (n = 516) and clinical staff (n = 30) was carried out. We analyzed 705 serological tests for SARS-CoV-2 sampled between 17 May 2020 (the first working day after lockdown release) up to 1 December 2020, to assess the positivity rates for SARS-CoV-2 antibodies. Participants/materials setting methods We collected data on the serological status for IgM and IgG antibodies against SARS-CoV-2 in 516 triage-negative men (n = 123) and women (n = 393) undergoing ART at a private fertility center and 30 HCWs that were at work during the study period. Antibodies were detected with a capture chemiluminescence assay (CLIA) targeting the highly Immunogenic S1 and S2 domains on the virus spike protein. We also analyzed the molecular test results of the cases exhibiting a positive serology. Main results and the role of chance The data showed that 5.2% of the triage-negative ART patients had a positive serological result for SARS-CoV-2, with an overall conversion rate of 2.1% for IgG and 4.6% for IgM. There was no significant difference in seroprevalence between sexes. The small cohort (n = 30) of HCWs had a markedly increased seroprevalence (12.9% for Ig M and 22.6% for IgG). The highest seropositivity in our cohort was recorded in November (16.2%). The IgM positivity rates revealed significant monthly increments, paralleling official prevalence rates based on nasopharyngeal swabs. No positive molecular tests were identified in cases exhibiting a solitary positive IgG result. We show that despite a 6-fold increase in the number of ART patients with a positive serology between May and December 2020, most of our patients remain unexposed to the virus. The study was undertaken in a high-risk area for COVID-19, with a 20-times increase in the active cases across the study period. Limitations reasons for caution The geographical restriction, alongside the lack of running a second, differently-targeted immunoassay (orthogonal testing), could limit the generalizability and translation of our results to other fertility settings or other immunoassays. Wider implications of the findings The low positivity rates for IgG against the SARS-CoV-2 spike protein seen at the end of 2020 imply that most of the fertility patients are still at risk for SARS-CoV-2 infection. Until mass vaccination and other measures effectively diminish the pandemic, risk mitigation strategies must be maintained in the fertility units in the foreseeable future. Patients with a solitary IgG+ status are most likely 'non-infectious' and can elude further testing without giving up the strict use of universal protective measures. With increasing seroprevalences owing to infection or vaccination, and with the consecutive increase in test performance, it is possible that serological screening of ART patients might be more cost-effective than PCR testing, especially for the many patients with repeat treatments/procedures in a time-frame of months. Study funding/competing interests This research received no external funding. All authors declare having no conflict of interest with regard to this trial.