The Management of Reno-Ureteral Lithiasis - from Emergency Presentation to Definitive Treatment.

Introduction: The aim of our study was to retrospectively evaluate the stone-free rate after the second intervention for every performed procedure (semirigid ureteroscopy, flexible ureteroscopy, semirigid plus flexible ureteroscopy and percutaneous nephrolithotomy). Materials and methods: A total of 149 patients, who came to the emergency room of "Saint John" Emergency Clinical Hospital, Bucharest, Romania, with acute renal pathology suggesting the presence of renal and/or ureteral lithiasis confirmed by imagining (x-ray, ultrasonography or computer tomography), were included in this retrospective study, which was conducted between September 2021 and September 2022. All selected patients had an indication of emergency surgical intervention that consisted of a double-J stent mounting. We analyzed the stone-free rate after the secondary intervention, which was one of the following procedures: semirigid ureteroscopy, flexible ureteroscopy, combined semirigid and flexible ureteroscopy (F-URS), and percutaneous nephrolithotomy (PCNL). Patients came back for the secondary intervention and were reevaluated using imaging techniques. Results:Endoscopic procedures were performed by 14 surgeons over a time period of two to six weeks after the initial stenting procedure. Encrusted stents were encountered in four cases and in five cases the patients were admitted with obstruction of previously inserted stents. From the total of 149 patients, 68 (45,6%) subjects underwent semirigid ureteroscopy, with a stone-free rate of 86% (59 cases), 32 (21,4%) F-URS, with a stone-free rate of 90,6% (30 cases), 41 (27,5%) combined flexible and semirigid ureteroscopy, with a stone-free rate of 90,24% (37 cases), and eight (5,3%) patients received PCNL, with a stone-free rate of 75% (six cases). Overall stone-free rate for all procedures was 90,06%. The mean operative time was 23 minutes. No major incidents or complications occurred during the procedures. Conclusion:The emergency pre-stenting before the definitive treatment of reno-ureteral lithiasis is a safe procedure. Flexible ureteroscopy was the most successful secondary intervention, with the highest rate of achieving stone-free status.

The Influence of SARS-CoV-2 on Minimally Invasive Therapeutic Approach for Benign Prostatic Hyperplasia.

Introduction: The COVID-19 pandemic definitely changed the management of patients with benign prostatic hyperplasia (BPH). This study followed the modalities of treatments in patients with BPH associated with SARS-CoV-2 attending the Urology Clinic of "Sf. Ioan" Emergency Clinical Hospital, Bucharest, Romania. Material and methods:The present study included 81 patients (mean age 63.2 years, age range 55-87 years) with SARS-CoV-2 and BPH who were admitted to our Urology Department between January 2021 and January 2022. The diagnosis of SARS-CoV-2 was based on the PCR test and that of BPH by using the diagnostic triad consisting of digital rectal examination, PSA, free PSA and ultrasound examination. It should be noted that some of the hospitalized patients were following treatment with alpha blockers and/or 5-alpha-reductase inhibitors at the time of admission. Results:Out of the 81 hospitalized cases, 13 required emergency endoscopic intervention under spinal anaesthesia (TURP or TURisP) for haemostasis because those patients presented with persistent haematuria which did not respond to conservative treatment. A number of 17 cases showed acute urinary retention during hospitalization and a urethrovesical catheter was fitted and will be re-evaluated urologically after the COVID episode. Of the remaining 51 subjects with BPH, 17 already had chronic urinary retention on admission, with urethrovesical probe present, 13 cases began during hospitalization with alpha-blocker treatment associated with 5-alpha-reductase inhibitors; meanwhile, there were no urological interventions to modify the treatment regimen in the remaining 21 patients, who were strictly managed on the side of COVID-19 infection. Conclusion:There was no clear influence of the evolution of patients with BPH due to SARS-CoV-2 pathology, and the general management trend was to delay chronic cases until the time of viral infection remission.

FSH RECEPTOR AND FSH BETA CHAIN POLYMORPHISM INVOLVEMENT IN INFERTILITY AND ENDOMETRIOSIS DISEASE.

OBJECTIVES: The purpose of this study was to evaluate the association between the follicle-stimulating hormone (FSH) receptor (c.-29G>A) and FSH beta chain (c.-280G>T) polymorphisms and endometriosis in Romanian women. MATERIAL AND METHODS: We performed the polymorphic analysis of the FSH receptor gene and FSH beta chain in 44 patients with endometriosis and 34 controls. Genomic DNA was obtained from peripheral blood and polymorphisms were investigated using restriction fragment length polymorphism analysis (RFLP). RESULTS: There were no significant differences in genotype frequencies of FSH receptor gene between endometriosis patients and controls. For the heterozygous type of the FSH receptor polymorphism (c.-29G>A) we did not find a significant difference in its frequency between patients with minimal/mild and moderate/severe endometriosis (p = 0.136). Also, the FSH beta chain (c.-280G> T) polymorphism frequency was not significantly associated with the severity of endometriosis (p = 0.966). CONCLUSIONS: FSH receptor and FSH beta chain polymorphisms do not seem to influence the severity of endometriosis, but they could be correlated with female infertility (primary or secondary), therefore further studies are required to debate this topic.

Efficient uptake and retention of iron oxide-based nanoparticles in HeLa cells leads to an effective intracellular delivery of doxorubicin.

The purpose of this study was to construct and characterize iron oxide nanoparticles (IONPCO) for intracellular delivery of the anthracycline doxorubicin (DOX; IONPDOX) in order to induce tumor cell inactivation. More than 80% of the loaded drug was released from IONPDOX within 24 h (100% at 70 h). Efficient internalization of IONPDOX and IONPCO in HeLa cells occurred through pino- and endocytosis, with both IONP accumulating in a perinuclear pattern. IONPCO were biocompatible with maximum 27.9% ± 6.1% reduction in proliferation 96 h after treatment with up to 200 µg/mL IONPCO. Treatment with IONPDOX resulted in a concentration- and time-dependent decrease in cell proliferation (IC50 = 27.5 ± 12.0 µg/mL after 96 h) and a reduced clonogenic survival (surviving fraction, SF = 0.56 ± 0.14; versus IONPCO (SF = 1.07 ± 0.38)). Both IONP constructs were efficiently internalized and retained in the cells, and IONPDOX efficiently delivered DOX resulting in increased cell death vs IONPCO.

Arterial hypertension in patients with atrial fibrillation in Europe: A report from the EURObservational Research Programme pilot survey on atrial fibrillation.

BACKGROUND: Hypertension (HTN) is the most prevalent co-morbidity among atrial fibrillation (AF) patients; the relationship between the two is bidirectional, with an incremental effect on adverse outcomes. PURPOSE: To study clinical features, treatment patterns and 1year outcomes amongst AF patients with HTN in the EURObservational Research Programme Atrial Fibrillation (EORP-AF) Pilot Registry, a prospective multi-national survey conducted by the European Society of Cardiology in 9 European countries. METHODS: Of 3119 enrolled AF patients, 2194 were diagnosed with HTN (AF-HTN) and 909 were normotensive (AF-NT) (16 patients had unknown HTN status). We compared baseline clinical features, management strategy and 1-year outcomes in terms of all-cause death, cardiovascular (CV) death, and any thrombosis-related event (TE: stroke, transient ischemic attack, acute coronary syndrome, coronary intervention, cardiac arrest, peripheral/pulmonary embolism) in AF-HTN vs AF-NT patients. RESULTS: The AF-HTN patients had more prevalent CV risk factors and comorbidities (median CHA2DS2-VASc score (IQR) 4 (3, 5) in AF-HTN, versus 2 (1, 3) in AF-NT; p<0.01). Crude rate of all-cause death and any TE event was higher in AF-HTN (194 (11.2%) versus 60 (8.2%), p=0.02). Kaplan-Meier analysis curves for death by hypertensive status showed no significant differences between the subgroups (log rank test, p=0.22). On logistic regression analysis, HTN did not emerge as an independent risk factor for outcomes (OR 1.08, 95% CI 0.76-1.54). CONCLUSION: AF-HTN patients have a higher prevalence of comorbidities and this conferred a higher risk for a composite endpoint of all-cause death and thromboembolic events. In this cohort HTN did not independently predict all-cause mortality at 1-year.

Quality of Life-a Goal for Schizophrenia's Therapy.

Quality of Life (QOL) assessment represents a good instrument to monitor the evolution of schizophrenia and the treatment's outcomes. The present study has evaluated the relationship between the level of the QOL and different socio-demographical and clinical factors. Lower QOL for schizophrenic persons was influenced by the severity of symptoms and cognitive deficits, while same low level of QOL could be considered an indicator for suicidal behavior. The correct therapeutically management of individuals with schizophrenia could lead to better outcomes in terms of life satisfaction of patients and response to the treatment's strategies.

Social Functioning in Schizophrenia Clinical Correlations.

Schizophrenia remains one of the major psychiatric disorder with huge social and economic costs for the individual and community. The role of psycho-social factors is important both on the etiopathogenesis of the illness and its evolution, lack of social functioning and associated stress have impact on everyday life of people with this diagnosis. Our study of 100 subjects with schizophrenia has showed significant correlations between clinical and social items: bigger number of admissions, longest duration of the evolution, cognitive deficits, smoking, suicidal behavior, age, marital status, smoking, level of perceived stress. The social functioning was influenced by these factors, and the therapeutically management during the hospitalization does not showed an improvement of the social function.

Microemulsion-made gadolinium carbonate hollow nanospheres showing magnetothermal heating and drug release.

Gadolinium carbonate (Gd2(CO3)3) hollow nanospheres and their suitability for drug transport and magnetothermally-induced drug release are presented. The hollow nanospheres are prepared via a microemulsion-based synthesis using tris(tetramethylcyclopentadienyl)gadolinium(iii) and CO2 as the starting materials. Size, structure and composition of the as-prepared Gd2(CO3)3 hollow nanospheres are comprehensively validated by several independent analytical methods (HRTEM, HAADF-STEM, DLS, EDXS, XRD, FT-IR, DTA-TG). Accordingly, they exhibit an outer diameter of 26 ± 4 nm, an inner cavity of 7 ± 2 nm, and a wall thickness of 9 ± 3 nm. As a conceptual study, the nanocontainer-functionality of the Gd2(CO3)3 hollow nanospheres is validated upon filling with the anti-cancerogenic agent doxorubicin (DOX), which is straightforward via the microemulsion (ME) strategy. The resulting DOX@Gd2(CO3)3 nanocontainers provide the option of multimodal imaging including optical and magnetic resonance imaging (OI, MRI) as well as magnetothermal heating and drug release. As a proof-of-concept, we could already prove the intrinsic DOX-based fluorescence, a low systemic toxicity according to in vitro studies as well as the magnetothermal effect and a magnetothermally-induced DOX release. In particular, the latter is new for Gd-containing nanoparticles and highly promising in view of theranostic nanocontainers and synergistic physical and chemical tumor treatment.

Novel bioactive glass-AuNP composites for biomedical applications.

The bioactive glasses doped with gold nanoparticles (AuNPs) are very attractive materials due to their potential in medical applications. In the present study Pluronic-nanogold hybrid nanoparticles were introduced during the sol-gel route of the SiO2-CaO-P2O5 glasses preparation. The obtained samples were characterized by UV-vis spectroscopy, X-ray diffraction, FT-IR spectroscopy, transmission electron and scanning electron microscopy and afterwards they were investigated in terms of bioactivity, protein adsorption and cells viability. The in vitro bioactivity assessment shows the increase of the number of agglomerated spherical shapes of apatite layers for all Au containing samples, but apatite like structure sizes are influenced by the AuNP content. Beside the spherical shapes, three-dimensional flower-like nanostructures were observed on the surface of the glass with 0.2mol% Au2O. Zeta potential and fluorescence spectroscopy measurements evidenced that the amount of serum albumin adsorbed onto the composites surface increases with the AuNP content. FT-IR measurements point out that the secondary structure of the adsorbed proteins presents few minor changes, indicating biocompatibility of the AuNP doped glasses. The good proliferation rate of Human keratinocytes cells obtained in the presence of samples with 0.15 and 0.2mol% Au2O is comparable with the values achieved from free AuNP, fact that proves the preservation of AuNP properties after their incorporation inside the bioactive glass matrices.

Bioactive and biocompatible copper containing glass-ceramics with remarkable antibacterial properties and high cell viability designed for future in vivo trials.

In the present study our interest is focused on finding the efficiency of 60SiO2·(32 - x)CaO·8P2O5·xCuO (mol%) glass-ceramics, with 0 ≤ x ≤ 4 mol%, in terms of bioactivity, biocompatibility, antibacterial properties and cell viability in order to determine the most appropriate composition for their further use in in vivo trials. The sol-gel synthesized samples show a preponderantly amorphous structure with a few crystallization centers associated with the formation of an apatite and calcium carbonate crystalline phases. The Fourier Transform Infrared (FT-IR) spectra revealed slightly modified absorption bands due to the addition of copper oxide, while the information derived from the measurements performed by transmission electron microscopy, UV-vis and electron paramagnetic resonance spectroscopy showed the presence of ions and metallic copper species. X-Ray photoelectron spectroscopic analysis indicated the presence of copper metallic species, in a reduced amount, only on the sample surface with the highest Cu content. Regarding in vitro assessment of bioactivity, the results obtained by X-ray diffraction, FT-IR spectroscopy and scanning electron microscopy, demonstrated the formation of a calcium phosphate layer on all investigated sample surfaces. The inhibitory effect of the investigated samples was more significant on the Pseudomonas aeruginosa than the Staphylococcus aureus strain, the sample with the lowest concentration of copper oxide (0.5 mol%) being also the most efficient in both bacterial cultures. This sample also exhibits a very good bactericidal activity, for the other samples it was necessary to use a higher quantity to inhibit and kill the bacterial species. The secondary structure of adsorbed albumin presents few minor changes, indicating the biocompatibility of the glass-ceramics. The cell viability assay shows a good proliferation rate on samples with 0.5 and 1.5 mol% CuO, although all glass-ceramic samples exhibited a good in vivo tolerance.

Monitoring the Laryngeal Nerves During Thyroidectomy. Initial 115 Cases Experience.

The lesions of the laryngeal nerves, despite low incidence, are the most severe long term complications after thyroidectomy. Visualization after careful dissection of the recurrent laryngeal nerve (RLN) is now the golden standard among thyroid surgeons. We assessed traditional landmarks for the identification of RLN and anatomic high risk situation. The study also presented our initial experience using neuro monitoring of RLN (IONM) during surgery. The results show a recognizable Zuckerkandl tubercle in 162 of the 222 cases (72,97%). After dissection RLN was found posterior from TZ in 154 cases (95,06%) and lateral from TZ in 8 cases (4,93%). The identification of the Zuckerkandl tubercle is a useful landmark for RLN localization. As concerning high risk situations we found 2 non recurrent laryngeal nerves (both on the right side). Extra laryngeal ramification of RLN is an anatomical reality with significant incidence (23,8% in our study) and major surgical involvement. Extra laryngeal ramification of RLN occurs more often between the cross point with inferior thyroid artery and larynx entry point. Monitoring the branches of RLN we obtain major EMG signal on the anterior one. The surgical meaning is that the anterior branch carries the most important motor fibers and we have to pay extra care in the correct identification and preservation of it. From a total of 222 visually identified RLN we have 215 nerves (96,84%) with positive EMG signal on monitoring. For 7 nerves (3,15%) we had no EMG signal. In 3 cases (2 total thyroidectomies and 1 lobectomy) involving 5 RLN there was a false negative result caused by electrode malposition or desoldering from endotracheal tube. Our initial experience shows that IONM is harmless, easy to handle and a useful tool for identifying the nerve and confirm its integrity. More extended studies are needed to show if intraoperative monitoring decreases the rate of RLN iatrogenic injury.

Corneal collagen cross-linking in keratoconus -- long-term prospective study.

PURPOSE: To determine the refractometric, keratometric and functional results 3 years after cross-linking therapy in patients with keratoconus. PATIENTS AND METHODS: Eighty-one patients in various stages of keratoconus were studied, all meeting eligibility criteria for the cross-linking technique. RESULTS: The results showed a decrease both in the K-values, of about 1.5 D, and in the refraction. Visual acuity improved by 1, 2 or 3 Snellen lines in 70% of the cases. CONCLUSIONS: The cross-linking technique is a modern method for stopping the progression of keratoconus.

Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06).

BACKGROUND: Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. PATIENTS AND METHODS: In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. RESULTS: The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1-5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8-3.8) months for no continuation; HR 0.74 (95% CI 0.58-0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63-1.1; P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30,000 USD per patient. CONCLUSIONS: Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4-6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00544700.

Plurietiologyc Possibilities and Difficulties of Seizures Management in Pregnancy.

Background - Pre-existing pathology, the development of acute new one strictly dependent of the pregnancy or an independent acute or chronic medical problems generate a highly complex disease that requires a nuanced interpretation of the pregnant women in an attempt to identify the most favorable solutions for evaluation and treatment. Case report - 26-28 weeks pregnant women, 23 years old, known epilepsy, HIV encephalitis and pulmonary TB in inconsistent treatment with prolonged seizure status. Emergency air evacuation from a third degree medical center to regional center ( first level) under general anesthesia. After 24 hours, conscious, without focal signs. Favorable ongoing pregnancy. Conclusions - Considering the medical history, we analyzed several possibly triggering and maintenance of the crisis elements so that clarification of them constituted the main challenges. Finding an imaging examination solution with minimal harming effect on the fetus was a key decision points. Tocography and excluding eclampsia as the etiology were the main reasons to refrain from practicing cesarean section and magnesium sulphate administration. Paralytic agents use, in particular succinylcholine was a decisional key point, considering the variation in serum cholynesterase activity in peripartum period. The phenytoin administration was also a difficult choice because of the risk of bradycardia to the fetus. No any adverse event as effects of the crisis and medical intervention on the mother reported to the newborn during the first 8 months of life, but cerebral palsy continues to concern before 24 months.

Hurdles and delays in access to anti-cancer drugs in Europe.

Demographic changes in the world population will cause a significant increase in the number of new cases of cancer. To handle this challenge, societies will need to adapt how they approach cancer prevention and treatment, with changes to the development and uptake of innovative anticancer drugs playing an important role. However, there are obstacles to implementing innovative drugs in clinical practice. Prior to being incorporated into daily practice, the drug must obtain regulatory and reimbursement approval, succeed in changing the prescription habits of physicians, and ultimately gain the compliance of individual patients. Developing an anticancer drug and bringing it into clinical practice is, therefore, a lengthy and complex process involving multiple partners in several areas. To optimize patient treatment and increase the likelihood of implementing health innovation, it is essential to have an overview of the full process. This review aims to describe the process and discuss the hurdles arising at each step.

Surgical treatment for pulmonary metastases in urogenital cancers.

INTRODUCTION: The malignant disease's ability to metastasize remains one of the major obstacles when treating patients with cancer. The indication of metastasectomy is currently limited to patients undergoing treatment of the primary tumor. Resections for lung metastases of high selected patients with urogenital cancer present minimal risks and can prolong survival. Prognostic factors that determine which patients will benefit from surgery are still unclear. MATERIAL AND RESULTS: This article presents a retrospective analysis of patients who underwent lung metastases resection between 2008 and 2013 in our clinic. Among 148 patients, 8 (5.41%) had lung metastases after urologic cancers (UC), 18 (12.16%) after genital cancers (GC), 13 (8.78%) after breast tumors and 109 (73.65%) had lung metastases from other type of tumors. The overall 6 months survival was 100% for UC, 94.44 for GC, 84.62% for BC and 87.16% for others. DISCUSSION AND CONCLUSION: The criteria for surgery proved to have a positive predictive value and what should be considered are the following: prolonged disease-free interval (DFI), unilateral disease, the absence of systemic pathologies, oncological margins resecability and less than 3 radioimagistic detectable metastases. A negative prognosis was observed in those with primary tumor in the cervix, at least 3 metastases and a tumor larger than 3 cm. To determine how to select surgical candidates for pulmonary metastasectomy more precisely, further analysis of prognostic factors is evident and the need for a prospective, randomized, multicenter study is clear.

Investigation of osteoblast cells behavior in polymeric 3D micropatterned scaffolds using digital holographic microscopy.

The effect of micropatterned polymeric scaffolds on the features of the cultured cells at different time intervals after seeding was investigated by digital holographic microscopy. Both parallel and perpendicular walls, with different heights, were fabricated using two-photon lithography on photopolymers. The walls were subsequently coated with polypyrrole-based thin films using the matrix assisted pulsed laser evaporation technique. Osteoblast-like cells, MG-63 line, were cultured on these polymeric 3D micropatterned scaffolds. To analyze these scaffolds with/without cultured cells, an inverted digital holographic microscope, which provides 3D images, was used. Information about the samples' refractive indices and heights was obtained from the phase shift introduced in the optical path. Characteristics of cell adhesion, alignment, orientation, and morphology as a function of the wall heights and time from seeding were highlighted.

Lesions of the laryngeal nerves during thyroidectomy - what's new?

Lesions to the laryngeal nerves, despite their low incidence, are the most severe long term complications after thyroidectomy.Visualization after careful dissection of the recurrent laryngeal nerve (RLN) is now the gold standard among thyroid surgeons. The Zuckerkandl tubercle (TZ) is a constant landmark for the identification of the RLN. Recent studies show the occurrence of two or more branches of RLN before entering the larynx. Knowledge about their existence could prevent lesions. Some high risk surgical situations are evidenced, such as: non recurrent laryngeal nerve emerging high from the vagus and the superior laryngeal nerve type Cernea 2. Several examination procedures are mandatory for a complete postoperative evaluation: video laryngoscopy and laryngeal electromyography (LEMG) bring valuable objective and prognostic data. However, due to the unpredictability of the synkynesis process, the prognosis of recovery in RLN injuries remains difficult.