Breast cancer risk assessment by Gail Model in women of Baghdad

Objectives: To assess the high incidence of breast cancer (BC) and the effect of its early diagnosis on decreasing morbidity and mortality among Iraqi women.Methods: A descriptive cross-sectional study was conducted and data were collected from 250 women in Baghdad by a questionnaire consisted of demographic and breast cancer risk (BCR) factors questions. Brest cancer risk was calculated using the BCR Assessment Tool (BCRAT) of the National Cancer Institute’s online version (Gail Model).Results: The average age of women was 45.46± 9.2 years. Twenty-six (10.4%) women have first degree relatives who had BC and three of them have more than one. More than half of the women 136 (54.4%) had their menarche at 12–13 years of age. Half of them 126 (50.4%) had their first birth at <30 year of age.The mean five year BCR for all women was 0.95 ± 1.4%, and 19 (7.6%) of them had a five year BCR ≥ 1.7%. Mean lifetime BCR up to age 90 years was 11.13 ± 4.7% and 6 (2.4%) women had high risk. Based on these findings, it can be suggested that employing Gail Model for BCR assessment can help healthcare providers in Iraq to estimate an individual’s probability of developing BC for screening and prevention.Keywords: Breast cancer risk; Gail Model; Ira

Coating of 1.4404 stainless steel by a combination of brazing and nitriding

In the current research, surface hardening of 1.4404 stainless steel was investigated. A hard Ni-containing coating was prepared by brazing at 1150 °C using a Ni foil with Si powder. The hardness behavior was increased by nitriding as well. The nitriding experiments were performed at low and high temperatures (460 and 640 °C) for a different period (3 and 6 h). The microstructure and material properties were characterized using scanning electron microscope (SEM), energy dispersive spectroscopy (EDS) and Micro Vickers hardness testing. Results show that the hard phase and the binding Ni foil were well distributed into the hard layer. The hard coating material was composed of a Si-phases and Ni-containing compound dispersion. After the nitriding, the hardness of the samples was increased with increasing the nitriding time and temperature and increasing the brazing time. The 10 min brazing and 6h nitriding at 640°C resulted in 32% higher hardness than the non-nitride sample. Strong metallurgical bonding is formed between the stainless steel substrate and the coating layer, as well as between the binding Ni foil and the hard phase; because of the mutual diffusion of alloying elements, the hardness of this hard coating was 2 to 3 times higher than the initial hardness of steel substrate

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Stability of high molecular weight iron nanoparticles and its implication for the treatment of patients with iron deficiency anemia

Hintergrund Eisennanopartikel wurden zur Behandlung von Eisenmangelanämie entwickelt und werden intravenös eingesetzt. Unter ihnen wurde 1949 Eisensaccharose (IS) (Venofer® von Vifor, Schweiz) entwickelt. Intravenöse Eisenpräparate sind Eisen-Kohlenhydrat-Komplexe, die entwickelt wurden, um hohe Eisendosen in einer stabilen, nicht toxischen Form abzugeben. Die Präparate bestehen aus kolloidalen Suspensionen von Eisenoxid-Nanopartikeln mit einem mehrkernigen Fe (III)-oxyhydroxid/Oxid-Kern, der von einem Kohlenhydratliganden umgeben ist. Aufgrund der Komplexität der intravenösen Eisenpräparate wird derzeit (von der EMA und der FDA) die Zulassung der generischen Arzneimittelfreisetzung von nicht- biologischen komplexen Arzneimitteln diskutiert. Die Zulassung von Generika basiert hauptsächlich auf der physikalisch-chemischen Äquivalenz. Mit der Verfügbarkeit von Eisensaccharose (ISS) in der Europäischen Union wurden jedoch Unterschiede in den klinischen Wirksamkeits- und Sicherheitsprofilen gegenüber dem Originalarzneimittel gemeldet. Die Hersteller des Originalpräparats behaupten, dass eine strenge Prüfung der generischen und der Originalpräparate für die Genehmigung des Inverkehrbringens obligatorisch ist. Probleme (1) Gibt es Unterschiede in der Menge an labilem Eisen in verschiedenen Chargen von originaler Eisensaccharose (Venofer), die für den Vertrieb in verschiedenen europäischen Ländern und für den US-amerikanischen Markt hergestellt wurden? (2) Unterscheidet sich die Menge an labilem Eisen in zwei generischen Eisensaccharosepräparaten signifikant von der Menge der ursprünglichen Eisensaccharosepräparate? Materialen und Methoden Eisenpräparate: (1) 8 Lots (Chargen) Eisensaccharose (Venofer®) aus EU- und Nicht-EU- Ländern. (2) Zwei andere Eisensaccharosepräparate, einschließlich eines generischen Eisensaccharose-ähnlichen Präparat, das in Österreich klinisch angewendet wird. Die Eisenpräparate wurden mit eisenfreiem HBS bis zur empfohlenen maximalen Verdünnung in (c (Eisen) = 1 mg / ml) verdünnt, 30 Minuten bei 25 C inkubiert und auf eine 96-Well-Platte gegeben, die mit einem Hydroxyethylstärke-gekoppelten Eisenchelator beschichtet war. Gleichzeitig wurden einige Wells mit Eisenstandards mit einem Eisenkonzentrationsbereich zwischen 0-1000mol / l inkubiert. Proben und Standards wurden in einem wasserdampfgesättigten Inkubator bei 37 C inkubiert. Labiles Eisen wurde durch den an die Platte gebundenen Chelator gebunden. Nach der Inkubation wurden die Proben und Standards aus den Vertiefungen entfernt und ungebundenes Eisen weggewaschen. Um die Menge des an den in der Platte gebundenen Eisenchelators in den Vertiefungen zu quantifizieren, wurde eine Nachweislösung, die einen nicht fluoreszierenden Eisenchelatorkomplex enthielt, in die Wells pipettiert und die Entwicklung eines eisenfreien fluoreszierenden Eisenchelators in einem Fluoreszenzplattenlesegerät bei 37C alle 30 Minuten während 4 Stunden gemessen. Ergebnise In diesem Assay konnte in allen Eisenpräparaten labiles Eisen in den Präparaten nachgewiesen werden. Die geringste Menge an chelatisierbarem Eisen war in Ferrum vitis (P9) vorhanden, gefolgt von Venofer aus Deutschland (P2-P4). Venofer-Chargen aus Griechenland (P1) und den USA (P6-P8) wiesen höhere Gehalte an labilem DFO-chelatierbarem Eisen auf. Obwohl sich Unterschiede in den Mittelwerten ergaben, gab es nur statistisch signifikante Unterschiede in der Konzentration an labilem Eisen zwischen zwei Chargen Venofer aus den USA (P7, P8) im Vergleich zu Ferrum vitis (P9). Es gab keinen signifikanten Unterschied zwischen der Eisensaccharose-Originalzubereitung (Venofer, Charge P1-P8) und dem generischen Eisensaccharosepräparate FerMed (P10). Daher können diese Chargen in Bezug auf den Gehalt an labilem Eisen als äquivalent angesehen werden, wenn sie in HBS, pH 7,4, verdünnt wurden. Schlussfolgerungen Die Ergebnisse dieser Studie zeigen, wie wichtig es ist, neue Assays zur Messung des Gehalts an labilem Eisen in intravenösen Eisenpräparaten zu entwickeln und Reduktionsmittel zur Beurteilung der Komplexstabilität zu verwenden. Zukünftig könnte dieser Test auf labiles Eisen in die Zulassungsanforderungen für die Prüfung neuer Eisensaccharoseprodukte als Sicherheitsparameter aufgenommen werden. Die Ergebnisse dieser Studie zeigen, dass es in verschiedenen Chargen von Venofer und FerMed in Puffer und in Gegenwart des Plasmaproteins Albumin keine signifikanten Unterschiede in der Menge des chelatierbaren labilen Eisens gibt. Beim Vergleich einer in Griechenland vertriebenen Charge von Venofer mit sieben in Deutschland und den USA vertriebenen Chargen derselben Präparats und dem in Österreich vertriebenen Generikum wurden erhebliche Unterschiede in der Abbaukinetik festgestellt.Abstract Background Iron nanoparticles were developed for the treatment of iron deficiency anemia and are used intravenously. Among them, Iron Sucrose (IS) (Venofer® from Vifor, Switzerland) was developed in 1949. Intravenous iron preparations are iron-carbohydrate complexes developed to deliver high doses of iron in a stable, non-toxic form. The preparations consist of colloidal suspensions of iron oxide nanoparticles with a polynuclear Fe (III)-oxyhydroxide/oxide core surrounded by a carbohydrate ligand. Due to the complexity of the intravenous iron preparations, there is an ongoing discussion (by EMA and FDA) regarding approval of generic drug release of non-biologic complex drugs. Authorization of generic pharmaceuticals is mostly based on physico-chemical equivalence. However, with the availability of iron sucrose similar (ISS) In the European Union, differences in clinical efficacy and safety profiles to the originator drug have been reported. Producers of the originator claim that rigorous testing of the generic vs. original preparations is mandatory for marketing authorization, however there are even for the original preparations no high throughput assays available for testing equivalence within lots of the original preparations. Problems There are two questions which will be addressed in this thesis: 1. Is there a variation in the amount of labile iron in different lots of original iron sucrose (Venofer) manufactured for distribution in different European countries and for the US market? 2. Is the amount of labile iron in two generic iron sucrose preparations significantly different from the original iron sucrose preparations? Materials and Methods Iron preparations: 1. 8 lots (batches) of iron sucrose (Venofer®) from from EU and non-EU countries. 2. 2 other iron sucrose preparations, including one generic iron sucrose similar preparation which is clinically used in Austria. 7 The iron preparations will be diluted with HBS iron free up to the recommended maximal dilution in 0,9% HBS iron free (c(iron) = 1mg/ml), incubated for 30min at 25C and added to a 96-well plate coated with hydroxyethyl starch coupled iron chelator. At the same time, some wells will be incubated with iron standards with an iron concentration range between 0-1000mol/l. Samples and standards are incubated in a humidified incubator at 37C. Labile iron will be bound by the chelator bound to the plate. Following incubation, samples and standards are removed from the wells and are washed 2x with distilled water, 1x with 5mM EDTA and 2x with distilled water, to remove sample and unbound iron. To quantify the amount of iron bound to the wells, a detection solution containing a non-fluorescent iron-chelator-complex will be added to the wells and development of iron-free fluorescent iron chelator will be measured in a fluorescence plate reader at 37C every 30 minutes over 4 hours. Results In this assay labile iron in the preparations could be detected in all iron preparations. The lowest amount of chelatable iron was present in Ferrum vitis (P9), followed by lots of Venofer obtained from Germany (P2-P4). Venofer lots from Greece (P1) and the USA (P6-P8) had higher levels of labile DFO-chelatable iron. Although there were differences in the means, there were only statistically significant differences in the labile iron concentration between two lots of Venofer from the USA (P7, P8) compared to Ferrum vitis (P9). There was no significant difference between iron sucrose original preparation (Venofer, lot P1-P8) and the generic iron sucrose similar preparation FerMed (P10). Therefore, in regard to labile iron content, these lots can be regarded as equivalent, when diluted in HBS, pH 7,4. Conclusions The results of this study show the importance to develop new assays to measure labile iron content of intravenous iron preparation and to use reductive agents to assess complex stability. In the future, this test for labile iron could be included in the marketing authorization requirements for testing new iron sucrose products as a safety parameter. The results of this study show that there are no significant differences in the amount of chelatable labile iron in different lots of Venofer and FerMed in buffer and in the presence of the plasma protein albumin. Significant lot to lot variation in the degradation kinetic were observed when a lot Venofer marketed in Greece was compared with seven lots of the same brand sold in Germany and the US market and the generic product sold in Austria.Paralleltitel laut Übersetzung des VerfassersMedizinische Universität Wien, Diplomarbeit, 2019(VLID)384899

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population

Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC EORP PPCM Registry

Aims: Hypertensive disorders occur in women with peripartum cardiomyopathy (PPCM). How often hypertensive disorders co-exist, and to what extent they impact outcomes, is less clear. We describe differences in phenotype and outcomes in women with PPCM with and without hypertensive disorders during pregnancy. Methods: The European Society of Cardiology PPCM Registry enrolled women with PPCM from 2012-2018. Three groups were examined: 1) women without hypertension (‘PPCM-noHTN’); 2) women with hypertension but without pre-eclampsia (‘PPCM-HTN’); 3) women with pre-eclampsia (‘PPCM-PE’). Maternal (6-month) and neonatal outcomes were compared. Results: Of 735 women included, 452 (61.5%) had PPCM-noHTN, 99 (13.5%) had PPCM-HTN and 184 (25.0%) had PPCM-PE. Compared to women with PPCM-noHTN, women with PPCM-PE had more severe symptoms (NYHA IV in 44.4% and 29.9%, p<0.001), more frequent signs of heart failure (pulmonary rales in 70.7% and 55.4%, p=0.002), higher baseline LVEF (32.7% and 30.7%, p=0.005) and smaller left ventricular end diastolic diameter (57.4mm [±6.7] and 59.8mm [±8.1], p<0.001). There were no differences in the frequencies of death from any cause, re-hospitalization for any cause, stroke, or thromboembolic events. Compared to women with PPCM-noHTN, women with PPCM-PE had a greater likelihood of left ventricular recovery (LVEF≥50%) (adjusted OR 2.08 95% CI 1.21-3.57) and an adverse neonatal outcome (composite of termination, miscarriage, low birth weight or neonatal death) (adjusted OR 2.84 95% CI 1.66-4.87). Conclusion: Differences exist in phenotype, recovery of cardiac function and neonatal outcomes according to hypertensive status in women with PPCM