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- Albertsson, Maria, et al.
(författare)
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Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer
- 2007
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Ingår i: Medical Oncology. - : Springer Science and Business Media LLC. - 1357-0560 .- 1559-131X. ; 24:4, s. 407-412
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The purpose of these studies was to compare efficacy and toxicity of docetaxel alone with the combination of gemcitabine and docetaxel for treatment of metastatic esophageal carcinoma. PATIENTS AND METHODS: These studies enrolled patients with histopathologically verified squamous cell carcinoma or adenocarcinoma of the esophagus or cardia. Between March 1997 and June 1999, 52 patients were enrolled in the initial Phase II study (Study 1). They were scheduled for treatment with docetaxel 100 mg/m2 every third week as a 1-h infusion. The second Phase II study between September 2000 and March 2003 included 65 patients (Study II). They were given docetaxel 30 mg/m2, administered as a 30-min i.v. infusion weekly for four times, followed by 2 weeks of rest, and gemcitabine starting with a dose of 750 mg/m2 (if well-tolerated 1,000 mg/m2) on days 1 and 15, followed by 3 weeks of rest. A new cycle began on day 36. Patients were premedicated with betamethasone 8 mg p.o. on the evening before, and 8 mg i.v. 30-60 min before the docetaxel infusion. Response was confirmed by computed tomography and assessed at 12 and 24 weeks. Toxicity was assessed according to WHO scales. RESULTS: In study I, 38 out of the 52 enrolled patients were valuable. Two patients experienced complete remission (CR) (5%), 10 patients partial remission (PR) (26%), nine patients stable disease (SD) (24%), and 17 patients showed progressive disease (PD) (45%). Toxicity mainly involved leukopenia, which in some cases required hospitalization and treatment with antibiotics. In Study II, 46 out of the 65 enrolled patients (70%) were assessable. Out of these, three patients (7%) had CR, eight patients (17%) had PR, 10 patients (22%) had SD, and 25 (54%) PD. Overall response was 24% while an additional 22% showed stable disease. Toxicity mainly consisted of leucopenia and pain. CONCLUSION: Docetaxel as a single agent is active in esophageal cancer, both in treatment naive and in previously treated patients with recurrent disease. The overall response rate was 31%, with a good-safety profile. The addition of gemcitabine is well tolerated, but adds no efficacy. Weekly administration of docetaxel may be less effective. It demonstrates moderate efficacy and the doses used provide an acceptable safety profile.
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- Frykholm, Peter, 1961-, et al.
(författare)
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Preoperative fasting in children. The evolution of recommendations and guidelines, and the underlying evidence
- 2024
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Ingår i: Best Practice & Research. - : Elsevier. - 1521-6896 .- 1532-169X. ; 38:2, s. 103-110
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Tidskriftsartikel (refereegranskat)abstract
- This review discusses the evolution of preoperative fasting guidelines and examines the incidence of pulmonary aspiration of gastric contents and suggested treatments. Nine guidelines developed by professional societies and published in peer-reviewed journals since 1994 were identified. The recommendations on preoperative fasting for various categories have undergone only small adaptations in the following three decades in pediatric anesthesia. We found twelve published studies of the incidence of pulmonary aspiration, which ranges from 0.6 to 12 in 10,000 anesthetics in children. However, this variation reflects differences in the definition of aspiration as well as differences in study design. The main risk factors identified are emergency surgery, ASA physical status, and patient age. Several additional risk factors have been suggested, including non-compliance to fasting guidelines. The duration of clear fluid fasting is not associated with an increased risk of pulmonary aspiration which may be reflected in future guideline updates in pediatric anesthesia.
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- Johansson, J., et al.
(författare)
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Gustavson syndrome is caused by an in-frame deletion in RBMX associated with potentially disturbed SH3 domain interactions
- 2024
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Ingår i: European Journal of Human Genetics. - : SPRINGERNATURE. - 1018-4813 .- 1476-5438. ; 32:3, s. 333-341
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Tidskriftsartikel (refereegranskat)abstract
- RNA binding motif protein X-linked (RBMX) encodes the heterogeneous nuclear ribonucleoprotein G (hnRNP G) that regulates splicing, sister chromatid cohesion and genome stability. RBMX knock down experiments in various model organisms highlight the gene's importance for brain development. Deletion of the RGG/RG motif in hnRNP G has previously been associated with Shashi syndrome, however involvement of other hnRNP G domains in intellectual disability remain unknown. In the current study, we present the underlying genetic and molecular cause of Gustavson syndrome. Gustavson syndrome was first reported in 1993 in a large Swedish five-generation family presented with profound X-linked intellectual disability and an early death. Extensive genomic analyses of the family revealed hemizygosity for a novel in-frame deletion in RBMX in affected individuals (NM_002139.4; c.484_486del, p.(Pro162del)). Carrier females were asymptomatic and presented with skewed X-chromosome inactivation, indicating silencing of the pathogenic allele. Affected individuals presented minor phenotypic overlap with Shashi syndrome, indicating a different disease-causing mechanism. Investigation of the variant effect in a neuronal cell line (SH-SY5Y) revealed differentially expressed genes enriched for transcription factors involved in RNA polymerase II transcription. Prediction tools and a fluorescence polarization assay imply a novel SH3-binding motif of hnRNP G, and potentially a reduced affinity to SH3 domains caused by the deletion. In conclusion, we present a novel in-frame deletion in RBMX segregating with Gustavson syndrome, leading to disturbed RNA polymerase II transcription, and potentially reduced SH3 binding. The results indicate that disruption of different protein domains affects the severity of RBMX-associated intellectual disabilities.
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| 11. |
- Martinsson, U., et al.
(författare)
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Why are not ALL Paediatric Patients Treated With Protons? : A Complete National Cohort From Sweden 2016-2019
- 2020
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 67:S4, s. S79-S79
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: A proton therapy (PT) facility – Skandion clinic- opened in Uppsala in august 2015. It was stated that all children inSweden, benefitting from PT, ought to be sent there. PT plans are prepared at six university-based radiotherapy (RT) centres and assessedby a national board. There are no additional costs for the families compared to other radiotherapy (RT) options, not even for travel and lodging.Methods: Since 2008 all children receiving RT with any modality areregistered in the Swedish Radtox registry. Inclusion is populationbased, prospective and complete. Radiation oncologists from the sixcentres performing paediatric RT retrospectively reviewed patientswho had not received PT.Results: 354 treatments were given, 252 (71%) were not PT. Thereasons for choosing conventional RT were dismal prognosis in 66patients, uncertainty due to internal movement and lack of motioncontrol technique at the PT centre in 63 patients, and lack of dosimetric advantage for protons in 47 patients. Infrequent reasons were lackof set up for CSI or very superficial treatment in the beginning [n=11],variations of air in the field [n=6], not robust treatment plan for otherreasons (mainly metal in the field) [n=6], gamma-knife/other stereotactic treatment [n= 5], brachytherapy [n=4], TBI [n=31], acute RT startnecessary [n=10], and social reasons [n=3].Conclusions: Even though proton therapy, due to less side effects,has been advocated to be the best treatment modality for children, this might not always be the case. Sometimes conventional RTmay be advantageous, despite the increased exit-dose, due to thewider penumbra of PT. Social needs and palliative situations may bemore important than an optimal dose-distribution. However, technical improvement of PT by application of gating and treatment planningsystems (TPS) handling dose-deposition uncertainties should make themodality available for a wider range of paediatric patients.
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- Nyblom, My, 1995, et al.
(författare)
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Strain-level bacterial typing directly from patient samples using optical DNA mapping
- 2023
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Ingår i: COMMUNICATIONS MEDICINE. - : Springer Science and Business Media LLC. - 2730-664X. ; 3:31
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Tidskriftsartikel (refereegranskat)abstract
- For bacterial infections, it is important to rapidly and accurately identify and characterize the type of bacteria involved so that optimal antibiotic treatment can be given quickly to the patient. However, current diagnostic methods are sometimes slow and cannot be used for mixtures of bacteria. We have, therefore, developed a method to identify bacteria directly from patient samples. The method was tested on two common species of disease-causing bacteria - Escherichia coli and Klebsiella pneumoniae - and it could correctly identify the bacterial strain or subtype in both urine samples and mixtures. Hence, the method has the potential to provide fast diagnostic information for choosing the most suited antibiotic, thereby reducing the risk of death and suffering. Nyblom, Johnning et al. develop an optical DNA mapping approach for bacterial strain typing of patient samples. They demonstrate rapid identification of clinically relevant E. coli and K. pneumoniae strains, without the need for cultivation. BackgroundIdentification of pathogens is crucial to efficiently treat and prevent bacterial infections. However, existing diagnostic techniques are slow or have a too low resolution for well-informed clinical decisions.MethodsIn this study, we have developed an optical DNA mapping-based method for strain-level bacterial typing and simultaneous plasmid characterisation. For the typing, different taxonomical resolutions were examined and cultivated pure Escherichia coli and Klebsiella pneumoniae samples were used for parameter optimization. Finally, the method was applied to mixed bacterial samples and uncultured urine samples from patients with urinary tract infections. Results We demonstrate that optical DNA mapping of single DNA molecules can identify Escherichia coli and Klebsiella pneumoniae at the strain level directly from patient samples. At a taxonomic resolution corresponding to E. coli sequence type 131 and K. pneumoniae clonal complex 258 forming distinct groups, the average true positive prediction rates are 94% and 89%, respectively. The single-molecule aspect of the method enables us to identify multiple E. coli strains in polymicrobial samples. Furthermore, by targeting plasmid-borne antibiotic resistance genes with Cas9 restriction, we simultaneously identify the strain or subtype and characterize the corresponding plasmids. Conclusion The optical DNA mapping method is accurate and directly applicable to polymicrobial and clinical samples without cultivation. Hence, it has the potential to rapidly provide comprehensive diagnostics information, thereby optimizing early antibiotic treatment and opening up for future precision medicine management.
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- Thoresen, L., et al.
(författare)
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The association of nutritional assessment criteria with health-related quality of life in patients with advanced colorectal carcinoma
- 2012
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Ingår i: European Journal of Cancer Care. - : Blackwell Publishing. - 0961-5423 .- 1365-2354. ; 21:4, s. 505-516
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Tidskriftsartikel (refereegranskat)abstract
- Health-related quality of life (QoL) is a goal in nutritional oncology but the association between nutritional status and QoL is rarely explored. The aim of the study was to investigate the association of nutritional assessment criteria with QoL in 50 patients with advanced colorectal carcinoma. A second aim was to investigate changes in body weight and QoL during a 3-month follow-up. Muscle mass, nutritional risk, malnutrition and cachexia according to three different criteria were assessed, as well as health-related QoL. At inclusion, 36 patients experienced weight loss, 10 patients sarcopenia, 25 were at nutritional risk, 16 were malnourished and 11, 14 and 31 patients had cachexia according to different criteria. All nutritional assessment criteria discriminated between groups of patients with worse or better QoL to varying degrees. Malnutrition and cachexia defined by the European Palliative Care Research Collaborative and adjusted for recent gain or stabilisation of body weight discriminated on most QoL scores. Weight loss at follow-up was associated with a decrease in several QoL scores. Recognition of weight loss as well as diagnosing malnutrition and cachexia should be the first steps in an interventional pathway to enhance nutritional status and QoL in patients with advanced colorectal carcinoma.
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