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A 30 years long data series on the infection dynamics of European eel (Anguilla anguilla L.) with the non-native invasive nematode Anguillicola crassus Kuwahara, Niimi & Hagaki, 1974 is presented. Parasite burden was evaluated for 30 years in inland and coastal waters in Mecklenburg-Western Pomerania from 1991 to 2020. The total prevalence, mean intensity and damage status of the swim bladders were very high during the first decade (1991–2000), and significantly decreased in both marine and freshwater eel populations in the following decades (2001–2010, 2011–2020). The parasite intensity of eels in coastal waters was significantly lower compared with the freshwater systems (61.3% vs 79.5% in the first decade), indicating the vulnerability of the parasites to brackish water conditions and the fact that the life cycle of A. crassus cannot be completed under high saline conditions. Eel caught in the western part of the Baltic Sea (west of Darss sill) had the lowest mean infection (51.8% in first decade) compared to the eastern part with 63.8%. Thus, besides different infection patterns caused by the environmental conditions, a temporal trend towards a reduced parasite intensity and a more balanced parasite–host relationship developed in the 30 years of interaction after the first invasion. Possible reasons and mechanisms for the observed trends in parasite–host interactions are discussed.

Bland–Altman limits of agreement are very popular in method comparison studies on quantitative outcomes. However, a straightforward application of Bland–Altman analysis requires roughly normally distributed differences, a constant bias, and variance homogeneity across the measurement range. If one or more assumptions are violated, a variance-stabilizing transformation (e.g., natural logarithm, square root) may be sufficient before Bland–Altman analysis can be performed. Sometimes, fractional polynomial regression has been used when the choice of variance-stabilizing transformation was unclear and increasing variability in the differences was observed with increasing mean values. In this case, regressing the absolute differences on a function of the average and applying fractional polynomial regression to this end were previously proposed. This review revisits a previous inter-rater agreement analysis on the Agatston score for coronary calcification. We show the inappropriateness of a straightforward Bland–Altman analysis and briefly describe the nonparametric limits of agreement of the original investigation. We demonstrate the application of fractional polynomials, use the Stata packages fp and fp_select, and discuss the use of degree-2 (the default setting) and degree-3 fractional polynomials. Finally, we discuss conditions for evaluating the appropriateness of nonstandard limits of agreement.

Ion Beam Analysis (IBA) utilizing MeV ion beams provides valuable insights into surface elemental composition across the entire periodic table. While ion beam measurements have advanced towards high throughput for mapping applications, data analysis has lagged behind due to the challenges posed by large volumes of data and multiple detectors providing diverse analytical information. Traditional physics-based fitting algorithms for these spectra can be time-consuming and prone to local minima traps, often taking days or weeks to complete. This study presents an approach employing a Mixture Density Network (MDN) to model the posterior distribution of Elemental Depth Profiles (EDP) from input spectra. Our MDN architecture includes an encoder module (EM), leveraging a Convolutional Neural Network-Gated Recurrent Unit (CNN-GRU), and a Mixture Density Head (MDH) employing a Multi-Layer Perceptron (MLP). Validation across three datasets with varying complexities demonstrates that for simple and intermediate cases, the MDN performs comparably to the conventional automatic fitting method (Autofit). However, for more complex datasets, Autofit still outperforms the MDN. Additionally, our integrated approach, combining MDN with the automatic fit method, significantly enhances accuracy while still reducing computational time, offering a promising avenue for improved analysis in IBA.

Diverting loop ileostomy has become routine in low anterior resection (LAR) for rectal cancer. The optimal time for stoma reversal is controversial. The aim of the present study was to compare the results after planned early (within 8–12 days) versus late (> 3 months) stoma reversal. The primary outcomes were morbidity and mortality, as measured by the Comprehensive Complication Index (CCI) within 30 days after stoma reversal, and the secondary outcomes were morbidity and mortality within 90 days after LAR. This was a multicentre trial including all patients scheduled for anterior low resection for rectal cancer with curative intent. Inclusion period was from April 2011 to December 2018. All patients were randomized 1:1 prior to surgery. Among 257 consecutive and eligible patients, a total of 214 patients were randomized: 107 patients to early stoma reversal and 107 to late reversal. A total of 68 patients were excluded for various reasons, and 146 patients completed the study, with 77 in the early reversal group and 69 in the late reversal group. The patients were asked to complete the Gastrointestinal Quality of Life Index before surgery (baseline) and at 6 and 12 months after LAR. Ostomy-related complications were evaluated by dedicated ostomy staff using the validated DET score. ClinicalTrials Identifier: NCT01865071. Fifty-three patients (69%) in the early reversal group and 60 patients (87%) in the late reversal group received the intended treatment. There were no significant differences in CCI within 90 days after index surgery with the LAR and within 30 days after stoma reversal between the two groups. There were no differences in patient-reported quality of life but significantly more stoma-related complications in the late reversal group. A total of 5 patients experienced anastomotic leakage (AL) after stoma reversal, 4 in the early reversal group and one in the late reversal group. Early and late stoma reversal showed similar outcomes in terms of overall complications and quality of life. The risk of developing anastomotic leakage after early ostomy reversal is a concern.

Background Multiple myeloma is a cancer in the bone marrow causing bone destruction. Patients experience various symptoms related to the disease and/or treatment, such as pain and fatigue, leading to poorer quality of life. The symptom burden might affect physical function and physical activity levels, posing a risk of physical deterioration. The aim was to investigate whether physical function in newly diagnosed patients with multiple myeloma differs from the reference values of the normal population and other cancer patients. Methods The study is a cross sectional descriptive analysis of a prospective cohort of 100 patients newly diagnosed with multiple myeloma. Four physical function tests were carried out; Six-Minute-Walk-Test, Sit-to-Stand-Test, grip strength and knee extension strength. Age and gender specific results of physical function from the multiple myeloma population were compared to normative data and to data from other cancer populations. Results Of the 100 patients included, 73% had bone disease and 55% received pain relieving medicine. Mean age was 67.7 years (SD 10.3). Patients with multiple myeloma had significantly poorer physical function compared to normative data, both regarding aerobic capacity and muscle strength, although not grip strength. No differences in physical function were found between patients with multiple myeloma and other cancer populations. Conclusions Physical function in newly diagnosed Danish patients with multiple myeloma is lower than in the normal population. Exercise intervention studies are warranted to explore the value of physical exercise on physical function. Trial registration ClinicalTrials.gov, ID NCT02439112 , registered 8 May 2015.

Background A randomized controlled pilot trial was conducted to assess if melanoma patients treated with immunotherapy had the number of grade 3 or 4 adverse events during treatment reduced by 50% using a tailored electronic patient-reported outcomes tool in addition to standard toxicity monitoring compared to standard monitoring alone. Secondary endpoints were: if more AEs were reported in the intervention group, if there was a difference between the two groups in the number of telephone consultations, extra out-patient visits, number of days in the hospital, days in steroid treatment and the time patients experienced grade 2 or higher toxicity. Patients and methods Melanoma patients receiving immunotherapy at the Department of Oncology, Odense University Hospital, Denmark participated. Standard care included assessment of AEs by a clinician before each treatment cycle using the Common Terminology Criteria for Adverse Events. In addition, patients randomized to the intervention reported their AEs weekly by an electronic PRO-tool based on the PRO-CTCAE platform. Results One hundred forty-six melanoma patients were randomized. In this study, we did not detect a difference between the two groups in the number of grade 3 or 4 AEs ( P  = 0.983), in the overall number of AEs ( P  = 0.560) or in the time the patients in the two groups experienced grade 2 or higher toxicity (0.516). The number of phone contacts was significantly higher in the intervention group ( P  = 0.009) and there was a tendency towards patients in the intervention group having more extra visits ( P  = 0.156). Conclusion It has been examined if the number of severe AEs for melanoma patients receiving immunotherapy could be reduced by involving the patients in the reporting of symptoms. The results do not justify the expansion of the pilot study into a regular phase III study with this particular set-up. However, a significant difference in the number of phone contacts was found as patients in the intervention group called more frequently, indicating that their attention to AEs was increased. Even though the use of an electronic PRO tool could not reduce the number of severe AEs in this melanoma population, a positive impact on other endpoints such as QoL, communication, or treatment-planning, cannot be excluded. Trial registration Clinicaltrials.gov NCT03073031 Registered 8 March 2017, Retrospectively registered.

Background Intestinal resection and a proximal stoma is the preferred surgical approach in patients with severe secondary peritonitis due to perforation of the small intestine. However, proximal stomas may result in significant nutritional problems and long-term parenteral nutrition. This study aimed to assess whether primary anastomosis or suturing of small intestine perforation is feasible and safe using the open abdomen principle with vacuum-assisted abdominal closure (VAC). Methods Between January 2005 and June 2018, we performed a retrospective chart review of 20 patients (> 18 years) with diffuse faecal peritonitis caused by small intestinal perforation and treated with primary anastomosis/suturing and subsequent open abdomen with VAC. Results The median age was 65 years (range: 23–90 years). Twelve patients were female (60%). Simple suturing of the small intestinal perforation was performed in three cases and intestinal resection with primary anastomosis in 17 cases. Four patients (20%) died within 90-days postoperatively. Leakage occurred in five cases (25%), and three patients developed an enteroatmospheric fistula (15%). Thirteen of 16 patients (83%) who survived were discharged without a stoma. The rest had a permanent stoma. Conclusions Primary suturing or resection with anastomosis and open abdomen with VAC in small intestinal perforation with severe faecal peritonitis is associated with a high rate of leakage and enteroatmospheric fistula formation. Trial registration The study was approved by the Danish Patient Safety Authority (case number 3-3013-1555/1) and the Danish Data Protection Agency (file number 18/28,404). No funding was received.

Purpose Rectal anastomoses have a persisting high incidence of anastomotic leakage. This study aimed to assess whether the use of a poly-ϵ-caprolactone (PCL) scaffold as reinforcement of a circular stapled rectal anastomosis could increase tensile strength and improve healing compared to a control in a piglet model. Method Twenty weaned female piglets received a stapled rectal anastomosis and were randomised to either reinforcement with PCL scaffold (intervention) or no reinforcement (control). On postoperative day five the anastomosis was subjected to a tensile strength test followed by a histological examination to evaluate the wound healing according to the Verhofstad scoring. Results The tensile strength test showed no significant difference between the two groups, but histological evaluation revealed significant impaired wound healing in the intervention group. Conclusion The incorporation of a PCL scaffold into a circular stapled rectal anastomosis did not increase anastomotic tensile strength in piglets and indicated an impaired histologically assessed wound healing.

Background Mother’s own milk (MOM) is important as the first nutrition for preterm infants, but mothers often struggle to initiate milk production right after preterm birth. If antenatal breastmilk expression (aBME) does not induce preterm labor when performed before term age, it could promote nutrition with MOM right after preterm birth. In this pilot study, we aimed to investigate whether aBME induces preterm labor among healthy nulliparous women from week 34 of pregnancy, to examine if aBME promotes the availability of MOM right after birth and affects breastfeeding outcomes. Methods Women were randomized to aBME (10 min 2 × daily) from week 34 of pregnancy until birth or to the control group. Both groups had a breastfeeding consultation between week 33 and 34 of pregnancy and were followed until eight weeks after birth. The primary outcome was gestational age (GA) at birth. Secondary outcomes were the availability of MOM and exclusive breastfeeding rates from 24 h to eight weeks after birth. Ranksum test and a posterior plot for the probability of non-inferiority were applied to the primary outcome. The availability of MOM is reported as medians and IQR. Breastfeeding outcomes were analyzed with mixed effects logistic regression. Results One hundred forty-four pregnant women were eligible for participation, 51 were excluded, and 33 declined participation/did not answer inclusion phone calls. 60 women were included and randomized. Primary outcome data were available in 55 women (28 in intervention, 27 in control). We found no difference in GA at birth between the two groups: median (IQR), 40 + 1(39 + 5:41 + 2) in intervention vs. 40 + 2 (39 + 4:41 + 1) in control, p  = 0.98. Antenatal expressed MOM was available at birth in most women in the intervention group (23/28, 82%), with a median of 52 mL during pregnancy. There was no statistically significant difference in breastfeeding outcomes. No adverse events were reported. Conclusions aBME performed by healthy nulliparous women from gestational week 34 did not induce preterm labor. In most women in the intervention group, MOM was available right after birth. The study results provide the basis for a trial among women at high risk for preterm birth. Trial Registration. clinicaltrials.gov (NCT05516199). Graphical Abstract

Background: We studied factors related to humoral response in solid organ transplant (SOT) recipients following a three-dose regimen of an mRNA-based SARS-CoV-2 vaccine. Method: This was a prospective study of SOT recipients who received a third homologous dose of the BNT162b2 (Pfizer–BioNTech) vaccine. The anti-spike S1 IgG response was measured using the SARS-CoV-2 IgG II Quant assay (Abbott Laboratories) with a cut-off of 7.1 BAU/mL. Multiple logistic regression was used to determine the factors associated with humoral response. Results: In total, 395 SOT recipients were included. Anti-spike IgG was detected in 195/395 (49.4%) patients after the second dose and 261/335 (77.9%) patients after the third dose. The overall mean increase in antibody concentration after the third dose was 831.0 BAU/mL (95% confidence interval (CI) 687.4–974.5) and 159 (47.5%) participants had at least a 10-fold increase in antibody concentration after the third dose. The increase in antibody concentration was significantly higher among patients with detectable antibodies after the second dose than those without. Cumulative time from transplantation and liver recipients was positively associated with an antibody response, whereas older age, administration of prednisolone, and proliferation inhibitors were associated with diminished antibody response. Conclusion: Although the third dose of the BNT162b2 vaccine improved humoral responses among SOT non-responders following the second dose, the overall response remained low, and 22.1% did not develop any response. Patients at risk of a diminished vaccine response require repeated booster doses and alternative treatment approaches.