| 1. |
- Gryback, Per, et al.
(author)
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Gastroparesis versus dyspepsia by intragastric meal distribution : new diagnostics and definitions ahead
- 2020
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In: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 55:2, s. 251-255
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Journal article (peer-reviewed)abstract
- Gastroparesis often presents a challenge to the practicing gastroenterologist. Postprandial symptoms with nausea and vomiting may not only lead to nutritional and metabolic consequences, but also significant disruption of social activities that often center around food. The treatment options that affect gastric function are limited and often disappointing. The female predominance, the mostly idiopathic and idiosyncratic nature of the illness, often with some common psychiatric co-morbidity, parallels other functional disorders of the gastrointestinal tract. These parallels have provided the rationale for studies investigating alternative diagnostic features of the gastric emptying test as employed in the clinical setting. Hence, not only the regular cut-offs of 60% or 10% gastric retention of a meal at 2 and 4 h, but also a new concept, the intragastric meal distribution at time 0 (IMD0) is now introduced as a plausible diagnostic feature that should be more aligned with the patients' symptoms as they appear in close connection with the meal. Impaired gastric accommodation with absence of fundic relaxation followed by dumping of the meal into antrum is suggested to be diagnostic for functional dyspepsia and gastroparesis. The diagnostic cut-off is considered when more than 57% of the meal is distributed to the distal part of the stomach immediately on food intake. This new diagnostic feature of the gastric emptying profile lend support to better understanding of the patients' symptoms and provides a new basis for pharmacological treatment options in gastroparesis that may provide an improved quality of life in affected individuals.
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| 2. |
- Lundquist, Patrik, et al.
(author)
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Barriers to the Intestinal Absorption of Four Insulin-Loaded Arginine-Rich Nanoparticles in Human and Rat
- 2022
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In: ACS Nano. - : American Chemical Society (ACS). - 1936-0851 .- 1936-086X. ; 16:9, s. 14210-14229
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Journal article (peer-reviewed)abstract
- Peptide drugs and biologics provide opportunities for treatments of many diseases. However, due to their poor stability and permeability in the gastrointestinal tract, the oral bioavailability of peptide drugs is negligible. Nanoparticle formulations have been proposed to circumvent these hurdles, but systemic exposure of orally administered peptide drugs has remained elusive. In this study, we investigated the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles displaying differing composition and surface characteristics, developed within the pan-European consortium TRANS-INT. The transport mechanisms and major barriers to nanoparticle permeability were investigated in freshly isolated human jejunal tissue. Cytokine release profiles and standard toxicity markers indicated that the nanoparticles were nontoxic. Three out of four nanoparticles displayed pronounced binding to the mucus layer and did not reach the epithelium. One nanoparticle composed of a mucus inert shell and cell-penetrating octarginine (ENCP), showed significant uptake by the intestinal epithelium corresponding to 28 ± 9% of the administered nanoparticle dose, as determined by super-resolution microscopy. Only a small fraction of nanoparticles taken up by epithelia went on to be transcytosed via a dynamin-dependent process. In situ studies in intact rat jejunal loops confirmed the results from human tissue regarding mucus binding, epithelial uptake, and negligible insulin bioavailability. In conclusion, while none of the four arginine-rich nanoparticles supported systemic insulin delivery, ENCP displayed a consistently high uptake along the intestinal villi. It is proposed that ENCP should be further investigated for local delivery of therapeutics to the intestinal mucosa.
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| 3. |
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| 4. |
- Abdellah, Tebani, et al.
(author)
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Integration of molecular profiles in a longitudinal wellness profiling cohort.
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Journal article (peer-reviewed)abstract
- An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies andimmune cell profiling, complementedwith gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.
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| 5. |
- Almdalal, T., et al.
(author)
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Clinical T1a Renal Cell Carcinoma, Not Always a Harmless Disease-A National Register Study
- 2022
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In: European Urology Open Science. - : Elsevier BV. - 2666-1691 .- 2666-1683. ; 39, s. 22-28
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Journal article (peer-reviewed)abstract
- Background: T1a renal cell carcinoma (RCC) is typically considered a curable dis-ease, irrespective of the choice of local treatment modality.& nbsp;Objective: To identify factors associated with the risk of local and distant recur-rence, and overall survival (OS) in patients with primary nonmetastatic clinical T1a RCC.& nbsp;Design, setting, and participants: A population-based nationwide register study of all 1935 patients with cT1a RCC, diagnosed during 2005-2012, identified through The National Swedish Kidney Cancer Register, was conducted.& nbsp;Outcome measurements and statistical analysis: Outcome variables were recur-rence (local or distant) and OS. Possible explanatory variables included tumor size, RCC type, T stage, surgical technique, age, and gender. Associations with disease recurrence and OS were evaluated by multivariable regression and Cox multivari-ate analyses, respectively.& nbsp;& nbsp;Results and limitations: Among 1935 patients, 938 were treated with radical nephrectomy, 738 with partial nephrectomy, and 169 with ablative treatments, while 90 patients had no surgery. Seventy-eight (4%) patients were upstaged to pT3. Local or metastatic recurrences occurred in 145 (7.5%) patients, significantly more often after ablation (17.8%). The risk of recurrence was associated with tumor size, upstaging, and ablation. Larger tumor size, disease recurrence, and older age adversely affected OS, whereas partial nephrectomy and chromophobe RCC (chRCC) were associated with improved survival. Limitations include register design and a lack of comorbidity or performance status data.& nbsp;Conclusions: Upstaging and recurrence occurred, respectively, in 4.0% and 7.5% of patients with nonmetastatic RCCs <= 4 cm. Tumor size upstaging and ablation were associated with the risk for recurrence, while tumor size and recurrence were associated with decreased OS. Patients with chRCC and partial nephrectomy had prolonged OS in a real-world setting.& nbsp;Patient summary: We studied factors that may influence the risk of disease recurrence and overall survival, in a large nationwide patient cohort having non metastatic renal cell carcinoma < 4 cm. Tumor size, tumor type, and treatment were associated with the risk of recurrence and overall death. Partial nephrectomy prolonged overall survival. (C)2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
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| 6. |
- Almdalal, Tarik, et al.
(author)
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Predictive characteristics for disease recurrence and overall survival in non-metastatic clinical T1 renal cell carcinoma : results from the National Swedish Kidney Cancer Register
- 2023
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In: Scandinavian journal of urology. - : Taylor & Francis. - 2168-1805 .- 2168-1813. ; 57:1-6, s. 67-74
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Journal article (peer-reviewed)abstract
- ObjectivePatients with clinical T1 renal cell carcinoma (cT1RCC) have risks for recurrence and reduced overall survival despite being in the best prognostic group. This study aimed to evaluate the association of different treatments on disease recurrence and overall survival using clinical and pathological characteristics in a nation-wide cT1RCC cohort.Materials and methodsA total of 4,965 patients, registered in the National Swedish Kidney Cancer Register (NSKCR) between 2005 and 2014, with ≥ 5-years follow-up were identified: 3,040 males and 1,925 females, mean age 65 years. Times to recurrence and overall survival were analyzed with Kaplan-Meier curves, log-rank test, and Cox regression models.ResultsAge, TNM-stage, tumor size, RCC-type, and performed treatment were all associated with disease recurrence. Patients selected for ablative treatments had increased risk for recurrent disease: hazard ratio (HR) = 3.79 [95% confidence interval (CI) = 2.69–5.32]. In multivariate analyses, age, gender, tumor size, RCC-type, N-stage, recurrence and performed treatment were all independently associated with overall survival. Patients with chRCC had a 41% better overall survival (HR = 0.59, 95% CI = 0.44–0.78; p < 0.001) than ccRCC. Patients treated with partial nephrectomy (PN) had an 18% better overall survival (HR = 0.83, 95% CI = 0.71–0.95, p < 0.001) than patients treated with radical nephrectomy.ConclusionsAge, gender, T-stage, tumor size, RCC type and treatment modality are all associated with risk of recurrence. Furthermore, age, male gender, tumor size, N-stage and recurrence are associated with reduced overall survival. Patients with chRCC, compared with ccRCC and pRCC patients, and PN compared with RN treated patients, had an advantageous overall survival, indicating a possible survival advantage of nephron sparing treatment.
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| 7. |
- Almotairi, Fawaz, et al.
(author)
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Chiari I malformation—neuropsychological functions and quality of life
- 2020
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 162:7, s. 1575-1582
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Journal article (peer-reviewed)abstract
- Objective: To assess the neuropsychological (NP) functioning and quality of life (QOL) before and 3months after surgery on adults with Chiari I malformation (CMI). Patients and methods: All adult patients who had been diagnosed with CMI were invited to participate. Those who participated were assessed using a Hospital Anxiety and Depression scale (HAD) and NP examinations. Their QOL was assessed using the self-reported life satisfaction checklist, LiSat-11 and the five-dimensional EuroQol measurement of health outcome, EQ-5D-5L. All assessments were carried out both before and 3months after surgery was performed. Demographic data and comorbidities were also registered. Results: Of the 11 patients who underwent NP assessment, the majority demonstrated cognitive functioning within the normal range. However, postoperatively, their performance in verbal learning, psychomotor speed, colour naming speed and the ability to manage interference through response selection and inhibition (aspects of executive functioning) was significantly improved. Thirteen patients completed QOL assessments. When LiSat-11 item domains were compared with those of healthy subjects, patients reported a lower level of satisfaction with their life quality both before and after surgery. However, the EQ-5D-5L measurements, i.e., the descriptive system and the visual analogue, indicated that their QOL of life was significantly improved after surgery. Conclusion: There is scarcely any literature documenting effects of surgery on the QOL of CMI patients. The study we present here breaks new ground by comparing pre- and postoperative NP functions in CMI. We also examine the value of surgery for improving both NP functions and QOL in CMI. © 2019, Springer-Verlag GmbH Austria, part of Springer Nature.
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| 8. |
- Andreasson, Anna, et al.
(author)
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An Increasing Incidence of Upper Gastrointestinal Disorders Over 23 Years : A Prospective Population-Based Study in Sweden
- 2021
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In: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 116:1, s. 210-213
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Journal article (peer-reviewed)abstract
- INTRODUCTION: We hypothesized that the prevalence of functional dyspepsia and gastroesophageal reflux disease in the community may be increasing.METHODS: Randomly selected adults were surveyed on 4 occasions: 1988 (n = 1,151, 21–79 years, response rate [rr] = 90%), 1989 (n = 1,097, 22–80 years, rr = 87%), 1995 (n = 1,139, 20–85 years, rr = 76%), and 2011 (n = 1,175, 20–93 years, rr = 63%).RESULTS: In functional dyspepsia, the odds of postprandial distress syndrome tripled over 23 years' follow-up (odds ratio [OR]: 3.55; 95% confidence interval [CI]: 2.60–4.84, mixed-effect regression analysis), whereas a small decrease in epigastric pain syndrome was observed (OR: 0.65, 95% CI: 0.42–1.00). The odds of reporting gastroesophageal reflux disease doubled (OR: 2.02; 95% CI: 1.50–2.73).DISCUSSION: The underlying mechanisms behind the increase in postprandial distress syndrome and gastroesophageal reflux disease remain to be determined.
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| 9. |
- Andrén, Kerstin, 1980, et al.
(author)
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Early shunt surgery improves survival in idiopathic normal pressure hydrocephalus
- 2021
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In: European Journal of Neurology. - : Wiley. - 1351-5101 .- 1468-1331. ; 28:4, s. 1153-1159
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Journal article (peer-reviewed)abstract
- Background and purpose To examine the effect of delayed compared to early planning of shunt surgery on survival, in patients with idiopathic normal pressure hydrocephalus (iNPH), a long-term follow-up case-control study of patients exposed to a severe delay of treatment was performed. Methods In 2010-2011 our university hospital was affected by an administrative and economic failure that led to postponement of several elective neurosurgical procedures. This resulted in an unintentional delay of planning of treatment for a group of iNPH patients, referred to as iNPH(Delayed) (n = 33, waiting time for shunt surgery 6-24 months). These were compared to patients treated within 3 months, iNPH(Early) (n = 69). Primary outcome was mortality. Dates and underlying causes of death were provided by the Cause of Death Registry. Survival was analysed by Kaplan-Meier plots and a Cox proportional hazard model adjusted for potential confounders. Results Median follow-up time was 6.0 years. Crude 4-year mortality was 39.4% in iNPH(Delayed) compared to 10.1% in iNPH(Early) (p = 0.001). The adjusted hazard ratio in iNPH(Delayed) was 2.57; 95% confidence interval 1.13-5.83, p = 0.024. Causes of death were equally distributed between the groups except for death due to malignancy which was not seen in iNPH(Delayed) but in 4/16 cases in iNPH(Early) (p = 0.044). Conclusions The present data indicate that shunt surgery is effective in iNPH and that early treatment increases survival.
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