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Incidence trends of surgical complications after oesophagectomy for oesophageal cancer: a population-based, nationwide cohort study in Finland over 30 years
Get PDFBACKGROUNDKnowledge on the incidence of surgical complications after oesophagectomy for oesophageal cancer in nationwide practice is scarce. The aim of this study was to assess complication trends after oesophagectomy in a nationwide, population-based, unselected cohort.METHODSAll patients undergoing oesophagectomy for oesophageal cancer in Finland in 1987-2016 were included. All complications defined by the Esophagectomy Complications Consensus Group (ECCG) were reported in three 10-year periods. Chi-square test and Kruskal-Wallis test were used to compare outcomes in these periods.RESULTSA total of 1493 patients were included. From 1987 to 1996 to 2007-2016, improvements were seen in the rate of major complications (49% vs. 43%, p = 0.039), length of hospital stay (19 vs. 14 days, median, p CONCLUSIONSThis study reports high postoperative morbidity after oesophagectomy in nationwide practice. Mortality has significantly improved during the years, and it appears that patients who would have died earlier, can now be rescued. While the relative occurrence of complications has remained constant, overall morbidity has decreased as the more severe outcomes have decreased.</p
Population Pharmacokinetic Quantification of CYP2D6 Activity in Codeine Metabolism in Ambulatory Surgical Patients for Model-Informed Precision Dosing
Get PDFBackground and Objective Codeine metabolism in humans is complex due to the involvement of multiple cytochrome P450 (CYP) enzymes, and has a strong genetic underpinning, which determines the levels of relevant CYP450 enzyme expression in vivo. Polymorphic CYP2D6 metabolises codeine to morphine via O-demethylation, while a strong correlation between CYP2D6 phenotype and opioidergic adverse efects of codeine is well documented. The aim of this study was to quantify the efect of CYP2D6 genotype on the biotransformation of codeine.Methods We conducted a prospective clinical trial with 1000 patients, during which ambulatory patients were administered 60 mg of codeine preoperatively and the association between CYP2D6 activity and morphine exposure across various CYP2D6 genotypes was quantifed using a population pharmacokinetic model. Plasma concentration data for codeine and its primary metabolites were obtained from 997 patients and CYP2D6 genotype was screened for study subjects, and respective sums of activity scores assigned for each CYP2D6 allele were used as covariates in model development.Results Our fnal model predicts the disposition of codeine and the formation of morphine, codeine-6-glucuronide and morphine-3-glucuronide adequately while accounting for variability in morphine exposure on the basis of CYP2D6 genotype. In agreement with previous results, patients with decreased function alleles (CYP2D6*10 and *41) showed varying levels of decrease in CYP2D6 activity that were inconsistent with increasing activity scores. Model simulations demonstrate that morphine concentrations in ultrarapid CYP2D6 metabolisers reach systemic concentrations that can potentially cause respiratory depression (over 9.1 ng/mL), and have 218% higher exposure (19 versus 8.7 µg · h/L, p Conclusions Our fnal model leads the way in implementing model-informed precision dosing in codeine therapy and identifes the use of genetic testing as an integral component in the efort to implement rational pharmacotherapy with codeine.</p
Surgical Residents´ Results Seem to be Non-Inferior Comparing to More Experienced Surgeons in Femoral Neck Fracture Osteosynthesis
Get PDFPurpose of the Study Femoral neck fracture osteosynthesis is usually performed by using dynamic hip screw (DHS) or multiple parallel cannulated screws (MCS). In orthopedic surgery training, certain hip fractures are one of the most common operations performed by residents. It has been questioned, whether residents can provide as safe treatment and patient outcomes as those of more experienced surgeons. The aim of this study was to evaluate the efect of surgical experience on risk of complications by comparing the surgical performance and clinical outcomes in femoral neck osteosyntheses between surgical residents and orthopaedic surgeons.Methods All patients with femoral neck fracture admitted to Helsinki and Uusimaa Hospital District (HUS) Hyvinkää Hospital from 2011 to 2016 were collected as research material. 88 hip fractures (87 patients) treated with DHS or MCS osteosyntheses were included in this study. The patients were divided into 2 groups, based on the surgeon’s experience: an orthopedic surgeon group (n=68) and a surgical resident group (n=20). All data from complications, reoperations, and the duration of operations were collected.Results There was no signifcant diference in characteristics of operated patients between orthopaedics and residents group. There was no signifcant diference in complications or re-operations between groups (p=0.4, p=0.2). Surgical residents had statistically longer surgical time (mean 76 min, 95% CI 62.92 min, mean 46 min, 95% Cl 42.51 min; p-valueConclusion Our results show that surgical residents´ outcomes in femoral neck fracture osteosynthesis seem to be as favorable as those of orthopedic surgeons; the operations just last slightly longer.</p
Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis
No full textInflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD-mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in particular, by the epithelial cells with a granular staining pattern in the cytosol. The same expression pattern was evidenced in both mouse models. Parp14-deficiency caused increased rectal bleeding as well as stronger epithelial erosion, Goblet cell loss, and immune cell infiltration in DSS-exposed mice. The absence of Parp14 did not affect the mouse colon bacterial microbiota. Also, the colon leukocyte populations of Parp14-deficient mice were normal. In contrast, bulk tissue RNA-Seq demonstrated that the colon transcriptomes of Parp14-deficient mice were dominated by abnormalities in inflammation and infection responses both prior and after the DSS exposure. Overall, the data indicate that Parp14 has an important role in the maintenance of colon epithelial barrier integrity. The prognostic and predictive biomarker potential of Parp14 in IBD merits further investigation
Tiederunoja
Get PDFTiederuno pohjautuu artikkeliin, jossa korostan, että estetisoiva katse ja havainnoille herkistyminen on voimavara ympäristön kokemista tutkittaessa. Valokuvahaastattelu tutkimusmenetelmänä paljastaa maisemasta sellaisia esteettisiä arvoja, joita siihen ei ole totuttu liittämään. Lähteenä Leinonen, P. 2022. Taidelähtöinen tutkimus lähiömaisemassa. Valokuva-aineisto arkisen maiseman esteettisten ominaisuuksien tarkastelussa. J@rgonia 20, 40: 112–138. http://urn.fi/URN:NBN:fi:jyu-202302131713</p
Finnish paediatric study found a low incidence of bacterial meningitis from 2011 to 2018 but a substantial proportion of nosocomial meningitis
Get PDFAimThis study examined the predisposing factors, clinical picture, bacterial aetiology and clinical outcomes of infants and children with bacterial meningitis (BM).MethodsThe medical records of patients under 16 years of age, treated by Turku University Hospital, Finland, from 2011 to 2018, were screened for meningitis using the International Classification of Diseases, Tenth Revision codes. Patients were included if bacteria were detected in cerebrospinal fluid (CSF) or other predefined laboratory variables indicated BM, despite CSF testing negative for bacteria. The Glasgow Outcome Scale (GOS) was used to determine outcomes.ResultsWe identified 37 children with BM: 22 infants aged 0-89 days and 15 children aged 90 days to 15 years. The overall incidence was approximately 5.7/100 000/year. Nosocomial meningitis was documented in 51%. Bacterial growth was detected in the CSF or blood cultures of the majority of patients (57%). Escherichia coli (14%), group B streptococcus (11%) and Streptococcus pneumoniae (8%) were the most common pathogens. There were 14% of patients with unfavourable outcomes, namely GOS scores of 1-4, but no deaths.ConclusionThe incidence of paediatric BM was low during the study period, but the proportion of nosocomial meningitis was substantial. The frequency of unfavourable long-term outcomes was relatively low.</p
Almost primes in almost all short intervals II
Get PDFWe show that, for almost all x, the interval (x, x + (log x)2.1] contains products of exactly two primes. This improves on a work of the second author that had 3.51 in place of 2.1. To obtain this improvement, we prove a new type II estimate. One of the new innovations is to use Heath-Brown's mean value theorem for sparse Dirichlet polynomials.</p
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
Get PDFUnderstanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 x10(-8)), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD
A new method of reconstructing images of gamma-ray telescopes applied to the LST-1 of CTAO
Get PDFContext. Imaging atmospheric Cherenkov telescopes (IACTs) are used to observe very high-energy photons from the ground. Gamma rays are indirectly detected through the Cherenkov light emitted by the air showers they induce. The new generation of experiments, in particular the Cherenkov Telescope Array Observatory (CTAO), sets ambitious goals for discoveries of new gamma-ray sources and precise measurements of the already discovered ones. To achieve these goals, both hardware and data analysis must employ cutting-edge techniques. This also applies to the LST-1, the first IACT built for the CTAO, which is currently taking data on the Canary island of La Palma. Aims. This paper introduces a new event reconstruction technique for IACT data, aiming to improve the image reconstruction quality and the discrimination between the signal and the background from misidentified hadrons and electrons. Methods. The technique models the development of the extensive air shower signal, recorded as a waveform per pixel, seen by CTAO telescopes’ cameras. Model parameters are subsequently passed to random forest regressors and classifiers to extract information on the primary particle. Results. The new reconstruction was applied to simulated data and to data from observations of the Crab Nebula performed by the LST-1. The event reconstruction method presented here shows promising performance improvements. The angular and energy resolution, and the sensitivity, are improved by 10 to 20% over most of the energy range. At low energy, improvements reach up to 22%, 47%, and 50%, respectively. A future extension of the method to stereoscopic analysis for telescope arrays will be the next important step.</p
