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31.
Muhammad Ahsan Javed Georg Beyer Nha Le Alessio Vinci Helen Wong Daniel Palmer Robert D. Morgan Angela Lamarca Richard A. Hubner Juan W. Valle Salma Alam Sumsur Chowdhury Yuk Ting Ma Livia Archibugi Gabriele Capurso Patrick Maisonneuve Albrecht Neesse Malin Sund Sebastian Krug 《Pancreatology》2019,19(1):97-104
Background
Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.Methods
A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors.Results
Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4–12.6), NAB+GEM 7.9 months (95%CI 6.2–10.0), other combinations 8.5 months (95%CI 7.7–9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4–5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1–3) with poor prognosis.Conclusion
Gemcitabine monotherapy was predominantly used in 2012–2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials. 相似文献32.
Changes of Marginal Bone Level in Patients with “Progressive Bone Loss” at Brånemark System® Implants: A Radiographic Follow‐Up Study over an Average of 9 Years 下载免费PDF全文
33.
André M Eriksson M Mölstad S Stålsbylundborg C Jacobsson A Odenholt I;Swedish Study Group on Antibiotic Use 《Scandinavian journal of infectious diseases》2005,37(11-12):863-869
A diagnosis-prescribing study was performed in 5 Swedish counties during 1 week in November in 2000 and repeated in 2002. The aim of the present study was to analyse data for children 0-15y of age who consulted a general practitioner with symptoms of an infection. During the 2 weeks studied, 4049 children were consulted. Respiratory tract infections (RTI) were the predominant diagnoses, above all among the youngest children, while the proportion of urinary tract infections and skin infections increased with increasing age. Between the y 2000 and 2002, the proportion of children allocated the diagnosis streptococcal tonsillitis and pneumonia decreased (p<0.01 and p<0.001, respectively) while the proportion of common cold increased (p<0.001). Antibiotic prescribing decreased from 55% to 48% (p<0.001) for respiratory infections between the years studied. The only significant changes in type of antibiotics prescribed were the increase of isoxazolylpenicillins (p<0.001) used for skin infection and the decrease of macrolides (p=0.001). A diagnostic test was used in more than half of the consultations. Of children allocated a RTI diagnosis, 36% were prescribed antibiotics when a C-reactive protein test was performed compared to 58% in those not tested. Further studies are needed in general practice to determine the optimal use of near-patient tests in children with RTI. 相似文献
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35.
Ambort D Johansson ME Gustafsson JK Nilsson HE Ermund A Johansson BR Koeck PJ Hebert H Hansson GC 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(15):5645-5650
MUC2, the major colonic mucin, forms large polymers by N-terminal trimerization and C-terminal dimerization. Although the assembly process for MUC2 is established, it is not known how MUC2 is packed in the regulated secretory granulae of the goblet cell. When the N-terminal VWD1-D2-D'D3 domains (MUC2-N) were expressed in a goblet-like cell line, the protein was stored together with full-length MUC2. By mimicking the pH and calcium conditions of the secretory pathway we analyzed purified MUC2-N by gel filtration, density gradient centrifugation, and transmission electron microscopy. At pH 7.4 the MUC2-N trimer eluted as a single peak by gel filtration. At pH 6.2 with Ca(2+) it formed large aggregates that did not enter the gel filtration column but were made visible after density gradient centrifugation. Electron microscopy studies revealed that the aggregates were composed of rings also observed in secretory granulae of colon tissue sections. The MUC2-N aggregates were dissolved by removing Ca(2+) and raising pH. After release from goblet cells, the unfolded full-length MUC2 formed stratified layers. These findings suggest a model for mucin packing in the granulae and the mechanism for mucin release, unfolding, and expansion. 相似文献
36.
37.
A Svee P Frykholm A Linder M Hakelius V Skoog D Nowinski 《The Journal of craniofacial surgery》2012,23(4):e299-e302
This article presents a treatment strategy for early release of interalveolar synechiae, aiming to facilitate early oral feeding and prevent temporomandibular joint ankylosis.The treatment results of 2 patients with van der Woude syndrome were retrospectively studied. Both patients underwent early surgical release of interalveolar synechiae under general anesthesia through fiberscopic nasal intubation. The 2 patients were treated at the ages of 6 and 14 days, respectively. The interincisival distances increased from 5 and 6 mm preoperatively to 11 and 10 mm immediately after surgery. This was increased further to 25 and 20 mm at long-term follow-up (6 and 24 months).In conclusion, synechiae between the upper and lower jaws can be safely treated at a very early age under general anesthesia with fiberscopic nasotracheal intubation. The purpose of early intervention in these cases is to facilitate oral feeding and prevent temporomandibular joint ankylosis. 相似文献
38.
39.
Annika Rosén Anna Feldreich Nakisa Dabirian Malin Ernberg 《Acta odontologica Scandinavica》2013,71(3):181-188
Objectives. The aims of the study were to investigate the influence of heterotopic noxious conditioning stimulation (HNCS) on pain thresholds in the orofacial and spinal regions and to find out whether there are gender differences in this respect. Material and Methods. Thirty healthy subjects (15 of each sex) with a mean (SD) age of 25.1 (4.4) years participated. Pain thresholds to electrical (EPT) and pressure stimuli (PPT) were recorded in the masseter muscle and 1st upper incisor (tooth), as well as in the fingertip, before, during, and 5 and 15 min after a cold pressor task to the contralateral hand immersed in ice-cold water for a maximum of 5 min. Results. With the exception of the EPT in the orofacial region, all pain thresholds increased during the HNCS and then returned to baseline during the 15 min follow-up. The significant changes in EPT were greater in the finger than in the tooth, while the changes in PPT were greater in the masseter muscle than in the finger. Electrical stimuli in the finger induced greater significant changes of pain thresholds than pressure. In the orofacial region, pressure induced greater significant changes in pain thresholds during HNCS than electrical stimuli did. The HNCS induced pain of high intensity and unpleasantness, i.e. varying between 5 and 10 on the numeric rating scale (NRS). There were no gender differences in the response to the HNCS. Conclusion. We conclude that, in general, HNCS induced by cold pressor stimulation increases pain thresholds, but the magnitude of the effect differs between the orofacial region and the finger and is influenced by the tissue and type of test stimuli. 相似文献
40.
Liana Ghazarian Julien Diana Lucie Beaudoin P?r G. Larsson Raj K. Puri Nico van Rooijen Malin Flodstr?m-Tullberg Agnès Lehuen 《Diabetes》2013,62(11):3785-3796
Invariant natural killer T (iNKT) cells belong to the innate immune system and exercise a dual role as potent regulators of autoimmunity and participate in responses against different pathogens. They have been shown to prevent type 1 diabetes development and to promote antiviral responses. Many studies in the implication of environmental factors on the etiology of type 1 diabetes have suggested a link between enteroviral infections and the development of this disease. This study of the pancreatropic enterovirus Coxsackievirus B4 (CVB4) shows that although infection accelerated type 1 diabetes development in a subset of proinsulin 2–deficient NOD mice, the activation of iNKT cells by a specific agonist, α-galactosylceramide, at the time of infection inhibited the disease. Diabetes development was associated with the infiltration of pancreatic islets by inflammatory macrophages, producing high levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α and activation of anti-islet T cells. On the contrary, macrophages infiltrating the islets after CVB4 infection and iNKT-cell stimulation expressed a number of suppressive enzymes, among which indoleamine 2,3-dioxygenase was sufficient to inhibit anti-islet T-cell response and to prevent diabetes. This study highlights the critical interaction between virus and the immune system in the acceleration or prevention of type 1 diabetes.Type 1 diabetes is characterized by the destruction of pancreatic islet β-cells by autoreactive CD4 and CD8 T cells, leading to low insulin production and incapacity to regulate blood glucose levels (1). Despite numerous studies, the etiology of type 1 diabetes remains elusive. Besides genetics (2–4), environmental factors such as viral infections have been suggested as triggers of type 1 diabetes (5–7). Most striking of these infections are the type B Coxsackieviruses belonging to the enterovirus genus whose genome and anti-Coxsackievirus antibodies were detected more frequently in the blood of recently diagnosed patients compared with healthy controls (8,9). Besides, enteroviral RNA or enteroviral particles were directly detected in the pancreas of type 1 diabetic patients, whereas they were undetectable in the pancreas of healthy donors (9,10). In a mouse model of type 1 diabetes, Serreze et al. (11) showed that diabetes can develop rapidly after Coxsackievirus B4 (CVB4) infection if mice had an advanced age and sufficient insulitis. Others have reported that inefficient islet β-cell response, viral dose, and replication rate as well as a lack of islet neogenesis could also promote accelerated diabetes development after CVB4 infection (12–14).Natural killer T (NKT) cells are CD1d-restricted, nonconventional T cells recognizing self and exogenous glycolipids. Most NKT cells express an invariant T-cell receptor α chain, Vα14-Jα18 (Vα14) in mice and Vα24-Jα18 in humans, and are named invariant NKT (iNKT) cells. They can promptly secrete copious amounts of interferon-γ (IFN-γ) and interleukin (IL)-4 and provide maturation signals to dendritic cells (DCs) and lymphocytes, thereby contributing to both innate and acquired immunity (15,16). iNKT cells are potent regulatory cells that can inhibit autoimmunity and promote immune responses against pathogens (1,17). Diabetes can be prevented in NOD mice by increasing iNKT cell numbers and by iNKT-cell stimulation with exogenous ligands such as α-galactosylceramide (αGalCer) (15,18,19). NOD mice protected from diabetes by iNKT cells have weak T helper 1 anti-islet β-cell responses (20). Indeed, iNKT cells can impair the differentiation of anti-islet CD4 and CD8 T cells, which become hyporesponsive or anergic (21). Contrary to their suppressive role in type 1 diabetes, iNKT cells can enhance immune responses to pathogens such as parasites, bacteria, and viruses (22,23).Our previous studies conducted in a murine model of type 1 diabetes with lymphocytic choriomeningitis virus infection revealed that iNKT cells could promote systemic antiviral CD8 T-cell responses while inhibiting deleterious anti-islet T-cell responses, thereby preventing type 1 diabetes (24,25). In the present study, we investigated the role of iNKT cells after CVB4 infection, revealing that diabetes development following CVB4 infection is associated with the infiltration of inflammatory macrophages into the pancreatic islets with subsequent activation of anti-islet T cells. However, the activation of iNKT cells during CVB4 infection results in the infiltration of suppressive macrophages into pancreatic islets. Indoleamine 2,3-dioxygenase (IDO) expressed by these macrophages was critical for the inhibition of diabetes development. 相似文献