Prospective Survey of AntibioticUtilization in Pediatric Hospitalized Patients to IdentifyTargets for Improvement of Prescription

Abstract. : Background: : The rise in the use of antibiotics has resulted in increasing health care costs and the emergence of resistant bacteria. Little is known about the general misuse of antibiotics in hospitalized children. We evaluated the utilization of antibiotics in a pediatric teaching hospital aiming to identify targets for improvement of prescription. Patients and Methods: : Clinical, radiological, laboratory and treatment data of patients hospitalized in a pediatric medical and a pediatric surgery ward were prospectively collected during a 6-week period. A subsequent review of the collected data by a pediatric infectious diseases specialist, taking into consideration existing in-house treatment guidelines, was carried out. Results: : A total of 125 (36%) of 349 patients was prescribed 246 antibiotics. The median length of hospital stay for children prescribed antibiotics was 5 days (range, 2-30 days) and for those not prescribed 3 days (1-32 days; p < 0.001). Of 154 patients in the medical ward, 64 (42%) received antibiotics, compared to 61 (31%) of 195 patients in the surgical ward (p < 0.05). Empirical prescriptions were more frequent than prophylactic ones, which were more frequent than therapeutic prescriptions (136 [55%] vs 94 [38%] vs 16 [7%]; p < 0.001). Overall, 85% of the prescriptions were considered justified. The rates of inappropriate prescriptions were similar in the medical and surgical ward, and higher for therapeutic (19%) or prophylactic treatment (18%) than for empirical treatment (12%). Higher inappropriate prescription rates were noted for macrolides than for co-trimoxazole and β-lactams (50% vs 18% and 15%, respectively; p < 0.05). Conclusion: : Efforts need to be undertaken towards continuous education of medical staff on judicious antibiotic use, as well as ensuring compliance with existing guidelines. Improvement in the availability of rapid diagnostic methods to discern viral from bacterial infections may help reduce the numbers of empiric therapies in favor of pathogen-targeted therapeutic treatment

Niwolumab w leczeniu raka nerkowokomórkowego w praktyce klinicznej

W ciągu ostatniej dekady nastąpił intensywny rozwój badań nad niwolumabem, jak i nad pozostałymi inhibitorami punktu kontrolnego. Jednym z nowotworów, w przypadku których istnieje najwięcej doświadczeń z niwolumabem, jest rak nerki. Wraz z coraz lepszym zrozumieniem mechanizmów działania komórkowej odpowiedzi immunologicznej, coraz lepiej rozumiemy, jakie jest miejsce niwolumabu wśród dostępnych w tym rozpoznaniu opcji terapeutycznych. W ostatnich kilku latach wyraźniej rysują się kierunki badań nad zwiększeniem skuteczności terapii inhibitorami punktu kontrolnego, toteż rozwijane są nowe skojarzenia leków immunokompetentnych. Niniejszy artykuł ma na celu przystępne przybliżenie onkologom praktykom kluczowych aspektów leczenia raka jasnokomórkowego nerki niwolumabem

BRAF — nowy cel terapeutyczny w raku jelita grubego

Mutacja BRAF V600E, o ugruntowanej już roli w leczeniu przerzutowego czerniaka, w ostatnich latach była intensywnie badana u chorych na przerzutowego raka jelita grubego. Występuje w około 10% przypadków tego nowotworu. Dowiedziono, iż jest negatywnym czynnikiem rokowniczym, chociaż nowsze prace wskazują na złożoną zależność tego efektu od stanu genów odpowiedzialnych za naprawę uszkodzeń DNA typu „mismatch”. Niezależnie od faktu, iż znaczenie predykcyjne mutacji BRAF V600E dla chemioterapii oraz leczenia celowanego pozostaje przedmiotem kontrowersji, konieczność odmiennego podejścia do leczenia systemowego pacjentów z tej grupy jest podnoszona w wytycznych międzynarodowych towarzystw naukowych. Badane są liczne opcje terapii: od intensyfikacji klasycznych schematów chemioterapii podawanych w pierwszej linii, po innowacyjne kombinacje leków celowanych mające na celu zniesienie efektu mutacji BRAF V600E na aktywację osiowych, dla karcynogenezy, szlaków transdukcji sygnału. Niniejsza praca przeglądowa ma na celu przybliżenie tego złożonego tematu onkologom zajmującym się na co dzień leczeniem nowotworów przewodu pokarmowego

BRAF — nowy cel terapeutyczny w raku jelita grubego

Mutacja BRAF V600E, o ugruntowanej już roli w leczeniu przerzutowego czerniaka, w ostatnich latach była intensywnie badana u chorych na przerzutowego raka jelita grubego. Występuje w około 10% przypadków tego nowotworu. Dowiedziono, iż jest negatywnym czynnikiem rokowniczym, chociaż nowsze prace wskazują na złożoną zależność tego efektu od stanu genów odpowiedzialnych za naprawę uszkodzeń DNA typu „mismatch”. Niezależnie od faktu, iż znaczenie predykcyjne mutacji BRAF V600E dla chemioterapii oraz leczenia celowanego pozostaje przedmiotem kontrowersji, konieczność odmiennego podejścia do leczenia systemowego pacjentów z tej grupy jest podnoszona w wytycznych międzynarodowych towarzystw naukowych. Badane są liczne opcje terapii: od intensyfikacji klasycznych schematów chemioterapii podawanych w pierwszej linii, po innowacyjne kombinacje leków celowanych mające na celu zniesienie efektu mutacji BRAF V600E na aktywację osiowych, dla karcynogenezy, szlaków transdukcji sygnału. Niniejsza praca przeglądowa ma na celu przybliżenie tego złożonego tematu onkologom zajmującym się na co dzień leczeniem nowotworów przewodu pokarmowego

Do solitary pancreatic metastases of renal-cell carcinoma indicate an indolent disease with a strong indication for aggressive local treatment? A case report with literature review

Renal-cell carcinoma (RCC) most often metastasizes to the lungs, liver, and brain. Metastases of RCC to the pancreas are very rare. In the last decade, only a few cases of metachronous metastasis of kidney cancer to the pancreas have been reported in the literature. This article presents a case report of a 75-year-old female patient with a 16-year history of treatment of clear-cell carcinoma of the kidney, in whom pancreatic metastases were detected twice. Renal-cell carcinoma may have an indolent course with late relapse or may show dissemination. It is important to establish new recommendations for long-term follow-up in patients after radical treatment

Land Policy for Flood Risk Management-Toward a New Working Paradigm

Flood risk management (FRM) aims to integrate necessary technical measures with environmental and societal approaches. Focusing on the process and governance of how to plan, implement, and maintain solutions therefore becomes essential. Among the different stakeholders, landowners are a key group to be considered. This contribution elaborates on the interconnections between land policy, FRM and private land ownership. It is based on the European COST Action network LAND4FLOOD, which brings together academics and stakeholders from various disciplines and more than 35 countries. We argue for a less project oriented and more process oriented approach, a focus on land management and more emphasis on small-scale measures. This represents a break with some of the recent working paradigms of FRM

Anthracycline-induced cardiotoxicity prevention with angiotensin-converting enzyme inhibitor ramipril in women with low-risk breast cancer : results of a prospective randomized study

Background: Anthracycline‑induced cardiotoxicity (AIC) remains the main long‑term irreversible side effect in malignancy survivors. Cardiotoxicity prevention is one of the most reasonable approaches. Aims: In this prospective randomized open‑label study, we aimed to verify whether ramipril protects from early‑onset AIC in women with breast cancer (BC). Methods: We analyzed data from 96 women (median age, 47 years) with BC after breast surgery, without significant cardiovascular diseases, who were eligible for adjuvant anthracyclines. They were randomized to a ramipril or control arm. Cardiotoxicity was estimated with repeat echocardiography and themeasurement of troponin I and N‑terminal fragment of the prohormone brain natriuretic peptide (NT‑proBNP) levels over 1‑year follow‑up. Anthracycline‑induced cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF), elevated biomarker levels, and/or occurrence of heart failure (HF) or cardiac death. Results: A decrease in LVEF above 10‑percent points occurred in 6.3% of ramipril patients and 18.5% ofcontrols (P = 0.15). No cases of HF, cardiac death, or LVEF decline below 50% were reported. The percentage of patients with elevated NT‑proBNP levels increased with time in controls (P = 0.003) and remained unchanged in the ramipril arm. At the end of follow‑up, an increase in NT‑proBNP levels was more common and decline was less common in the control than ramipril arm (P = 0.01). No significant differences in troponin levels were found between the study arms. Ramipril was well tolerated in normotensive women. Conclusions: In relatively young women with BC without serious comorbidities, who received anthracyclines, 1‑year treatment with ramipril exerts potentially protective effects on cardiotoxicity assessed with NT‑proBNP levels

Socialist Dandies International: East Europe, 1946-1959

This article maps the looks and lifestyle choices of small groups of young, like-minded people who emerged in the postwar Soviet Union and East Europe in the background of huge political, social, and cultural changes. With their androgynous bodies wrapped in drape jackets and narrow trousers, and their love of jazz and swing, these young men stood in a sharp contrast to the official ideology that promoted socialism as a new, pure, and highly rationalized project, its ideal robust and strong man, and its mass culture that insisted on educational and restrained forms of entertainment. Through the categories of dress, body, and big city, the article investigates the clashes, and the eventual truce, between the socialist streamlined and rationalized master narrative and the young dandies' fragmented and disordered narrative. The article argues that the socialist dandies were not politically minded, and that their challenge to the officially proclaimed values was informed by their adolescent recklessness and a general postwar desolation. They were declared state enemies because the socialist regimes did not allow for alternative types of modernity. Consequently, the authorities condemned the young dandies' looks and interests as cosmopolitan, because they originated in the West, and as artificial, since they belonged to the culture that had preceded a new socialist world

A Duplication CNV That Conveys Traits Reciprocal to Metabolic Syndrome and Protects against Diet-Induced Obesity in Mice and Men

The functional contribution of CNV to human biology and disease pathophysiology has undergone limited exploration. Recent observations in humans indicate a tentative link between CNV and weight regulation. Smith-Magenis syndrome (SMS), manifesting obesity and hypercholesterolemia, results from a deletion CNV at 17p11.2, but is sometimes due to haploinsufficiency of a single gene, RAI1. The reciprocal duplication in 17p11.2 causes Potocki-Lupski syndrome (PTLS). We previously constructed mouse strains with a deletion, Df(11)17, or duplication, Dp(11)17, of the mouse genomic interval syntenic to the SMS/PTLS region. We demonstrate that Dp(11)17 is obesity-opposing; it conveys a highly penetrant, strain-independent phenotype of reduced weight, leaner body composition, lower TC/LDL, and increased insulin sensitivity that is not due to alteration in food intake or activity level. When fed with a high-fat diet, Dp(11)17/+ mice display much less weight gain and metabolic change than WT mice, demonstrating that the Dp(11)17 CNV protects against metabolic syndrome. Reciprocally, Df(11)17/+ mice with the deletion CNV have increased weight, higher fat content, decreased HDL, and reduced insulin sensitivity, manifesting a bona fide metabolic syndrome. These observations in the deficiency animal model are supported by human data from 76 SMS subjects. Further, studies on knockout/transgenic mice showed that the metabolic consequences of Dp(11)17 and Df(11)17 CNVs are not only due to dosage alterations of Rai1, the predominant dosage-sensitive gene for SMS and likely also PTLS. Our experiments in chromosome-engineered mouse CNV models for human genomic disorders demonstrate that a CNV can be causative for weight/metabolic phenotypes. Furthermore, we explored the biology underlying the contribution of CNV to the physiology of weight control and energy metabolism. The high penetrance, strain independence, and resistance to dietary influences associated with the CNVs in this study are features distinct from most SNP–associated metabolic traits and further highlight the potential importance of CNV in the etiology of both obesity and MetS as well as in the protection from these traits