Patients with autoimmune liver disease have glucose disturbances that mechanistically differ from steatotic liver disease.

Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n = 19), primary biliary cholangitis (PBC, n = 15), and primary sclerosing cholangitis (PSC, n = 6). Healthy individuals (n = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n = 18) were included as controls. Blood samples were collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH and MASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early on in their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.

Primary autoimmune haemolytic anaemia is associated with increased risk of ischaemic stroke: A binational cohort study from Denmark and France.

Primary autoimmune haemolytic anaemia (AIHA) causes the destruction of red blood cells and a subsequent pro-thrombotic state, potentially increasing the risk of ischaemic stroke. We investigated the risk of ischaemic stroke in patients with AIHA in a binational study. We used prospectively collected data from nationwide registers in Denmark and France to identify cohorts of patients with primary AIHA and age- and sex-matched general population comparators. We followed the patient and comparison cohorts for up to 5 years, with the first hospitalization of a stroke during follow-up as the main outcome. We estimated cumulative incidence, cause-specific hazard ratios (csHR) and adjusted for comorbidity and exposure to selected medications. The combined AIHA cohorts from both countries comprised 5994 patients and the 81 525 comparators. There were 130 ischaemic strokes in the AIHA cohort and 1821 among the comparators. Country-specific estimates were comparable, and the overall adjusted csHR was 1.36 [95% CI: 1.13-1.65], p = 0.001; the higher rate was limited to the first year after AIHA diagnosis (csHR 2.29 [95% CI: 1.77-2.97], p < 10-9 ) and decreased thereafter (csHR 0.89 [95% CI: 0.66-1.20], p = 0.45) (p-interaction < 10-5 ). The findings indicate that patients diagnosed with primary AIHA are at higher risk of ischaemic stroke in the first year after diagnosis.

Body Contouring Surgery After Bariatric Surgery Improves Long-Term Health-Related Quality of Life and Satisfaction With Appearance: An International Longitudinal Cohort Study Using the BODY-Q.

OBJECTIVE: To examine health-related quality of life (HRQL) and satisfaction with appearance in patients who have undergone bariatric surgery (BS) with or without subsequent body contouring surgery (BCS) in relation to the general population normative for the BODY-Q. BACKGROUND: The long-term impact of BS with or without BCS has not been established using rigorously developed and validated patient-reported outcome measures. The BODY-Q is a patient-reported outcome measure developed to measure changes in HRQL and satisfaction with appearance in patients with BS and BCS. METHODS: Prospective BODY-Q data were collected from 6 European countries (Denmark, the Netherlands, Finland, Germany, Italy, and Poland) from June 2015 to February 2022 in a cohort of patients who underwent BS. Mixed-effects regression models were used to analyze changes in HRQL and appearance over time between patients who did and did not receive BCS and to examine the impact of patient-level covariates on outcomes. RESULTS: This study included 24,604 assessments from 5620 patients. BS initially led to improved HRQL and appearance scores throughout the first postbariatric year, followed by a gradual decrease. Patients who underwent subsequent BCS after BS experienced a sustained improvement in HRQL and appearance or remained relatively stable for up to 10 years postoperatively. CONCLUSIONS: Patients who underwent BCS maintained an improvement in HRQL and satisfaction with appearance in contrast to patients who only underwent BS, who reported a decline in scores 1 to 2 years postoperatively. Our results emphasize the pivotal role that BCS plays in the completion of the weight loss trajectory.

Doping-Induced Surface and Grain Boundary Effects in Ni-Rich Layered Cathode Materials.

In this work, the effects of dopant size and oxidation state on the structure and electrochemical performance of LiNi0.8Co0.1Mn0.1O2 (NCM811) are investigated. It is shown that doping with boron (B) which has a small ionic radius and an oxidation state of 3+, leads to the formation of a boron oxide-containing surface coating (probably Li3BO3), mainly on the outer surface of the secondary particles. Due to this effect, boron only slightly affects the size of the primary particle and the initial capacity, but significantly improves the capacity retention. On the other hand, the dopant ruthenium (Ru) with a larger ionic radius and a higher oxidation state of 5+ can be stabilized within the secondary particles and does not experience a segregation to the outer agglomerate surface. However, the Ru dopant preferentially occupies incoherent grain boundary sites, resulting in smaller primary particle size and initial capacity than for the B-doped and pristine NCM811. This work demonstrates that a small percentage of dopant (2 mol%) cannot significantly affect bulk properties, but it can strongly influence the surface and/or grain boundary properties of microstructure and thus the overall performance of cathode materials.

The Biological Activities of Polyether Ionophore Antibiotic Routiennocin is Independent of Absolute Stereochemistry.

Carboxylic polyether ionophores (CPIs) are among the most prevalent agricultural antibiotics (notably in the US) and these compounds have been in use for decades. The potential to reposition CPIs beyond veterinary use, e. g. through chemical modifications to enhance their selectivity window, is an exciting challenge and opportunity, considering their general resilience towards resistance development. Given the very large societal impact of these somewhat controversial compounds, it is surprising that many aspects of their mechanisms and activities in cells remain unclear. Here, we report comparative biological activities of the CPI routiennocin and two stereoisomers, including its enantiomer. We used an efficient convergent synthesis strategy to access the compounds and conducted a broad survey of antibacterial activities against planktonic cells and biofilms as well as the compounds' effects on mammalian cells, the latter assessed both via standard cell viability assays and broad morphological profiling. Interestingly, similar bioactivity of the enantiomeric pair was observed across all assays, strongly suggesting that chiral interactions do not play a decisive role in the mode of action. Overall, our findings are consistent with a mechanistic model involving highly dynamic behaviour of CPIs in biological membranes.

Surgical stress response in robot-assisted versus laparoscopic surgery for colon cancer (SIRIRALS): randomized clinical trial.

BACKGROUND: Evidence for the routine use of robotic technology and its impact on short-term outcomes in colon cancer surgery is lacking. The aim of this study was to compare the surgically induced systemic stress response and clinical and patient-reported outcomes for patients undergoing robot-assisted or laparoscopic colon cancer surgery. METHODS: In this double-blinded superiority RCT completed between August 2021 and March 2023, patients with stage 1-3 colon cancer were randomized in a 1 : 1 ratio to undergo either robot-assisted or laparoscopic colon cancer surgery. The primary outcome was changes in the systemic stress response, characterized by C-reactive protein expression in the first three postoperative days. Secondary outcomes were intraoperative and postoperative complications and patient-reported outcomes. The latter included quality of recovery-15 and pain intensity using a visual analogue scale. RESULTS: In total, 128 patients were screened for potential inclusion in this study; 50 patients (25 in the robot-assisted group and 25 in the laparoscopic group) were included in the final follow-up and analysis. The postoperative C-reactive protein response was higher on the first postoperative day in the laparoscopic group (mean difference = 19.88 mg/l, 95% c.i. 3.89-35.86; P = 0.045). No statistically significant differences were noted for C-reactive protein expression on the second and third postoperative days. CONCLUSION: Adopting robot-assisted surgery for stage 1-3 colon cancer is associated with a reduction in the surgical stress response. REGISTRATION NUMBER: NCT04687384 (http://www.clinicaltrials.gov).

Cardiac dysfunction in patients with cirrhosis and acute decompensation.

The prevalence of cirrhotic cardiomyopathy (CCM) has been reported as high as 60%-70% in patients with liver cirrhosis and is associated with various negative outcomes. There has been a growing understanding of CCM over recent years. Indeed, the development of imaging techniques has enabled new diagnostic criteria to be proposed by the Cirrhotic Cardiomyopathy Consortium. However, important unanswered questions remain over pathophysiological mechanisms, optimal diagnostic modalities and potential treatment options. While there has been an increasing volume of literature evaluating CCM, there is a lack of clarity on its implications in acute decompensation, acute-on-chronic liver failure and following interventions such as transjugular intrahepatic portosystemic shunt insertion and liver transplantation. This review aims to summarise the literature in these challenging domains and suggest where future research should focus. We conclude that systemic inflammation and structural myocardial changes are likely to be crucial in the pathophysiology of the disease, but the relative contribution of different components remains elusive. Furthermore, future studies need to use standardised diagnostic criteria for CCM as well as incorporate newer imaging techniques assessing both myocardial structure and function. Finally, while specific treatments are currently lacking, therapeutics targeting systemic inflammation, microbial dysbiosis and bacterial translocation are promising targets and warrant further research.

Investigation of luteal HCG supplementation in GnRH-agonist-triggered fresh embryo transfer cycles: a randomized controlled trial.

RESEARCH QUESTION: Does splitting the human chorionic gonadotrophin (HCG) support in IVF cycles triggered by a gonadotrophin-releasing hormone agonist result in a better progesterone profile? DESIGN: Randomized controlled three-arm study, performed at the Fertility Clinic, Odense University Hospital, Denmark. Patients with 12-25 follicles ≥12 mm were randomized into three groups: Group 1 - ovulation triggered with 6500 IU HCG; Group 2 - ovulation triggered with 0.5 mg GnRH agonist, followed by 1500 IU HCG on the day of oocyte retrieval (OCR); and Group 3 - ovulation triggered with 0.5 mg GnRH agonist, followed by 1000 IU HCG on the day of OCR and 500 IU HCG on OCR + 5. All groups received 180 mg vaginal progesterone. Progesterone concentrations were analysed in eight blood samples from each patient. RESULTS: Sixty-nine patients completed the study. Baseline and laboratory data were comparable. Progesterone concentration peaked on OCR + 4 in Groups 1 and 2, and peaked on OCR + 6 in Group 3. On OCR + 6, the progesterone concentration in Group 2 was significantly lower compared with Groups 1 and 3 (P = 0.003 and P < 0.001, respectively). On OCR + 8, the progesterone concentration in Group 3 was significantly higher compared with the other groups (both P<0.001). Progesterone concentrations were significantly higher in Group 3 from OCR + 6 until OCR + 14 compared with the other groups (all P ≤ 0.003). Four patients developed ovarian hyperstimulation syndrome in Group 3. CONCLUSION: Sequential HCG support after a GnRH agonist trigger provides a better progesterone concentration in the luteal phase.

Exercise in newly diagnosed patients with multiple myeloma: A randomized controlled trial of effects on physical function, physical activity, lean body mass, bone mineral density, pain, and quality of life.

Reduced physical function caused by bone destruction, pain, anemia, infections, and weight loss is common in multiple myeloma (MM). Myeloma bone disease challenges physical exercise. Knowledge on the effects and safety of physical exercise in newly diagnosed patients with MM is limited. In a randomized, controlled trial, we studied the effect of a 10-week individualized physical exercise program on physical function, physical activity, lean body mass (LBM), bone mineral density (BMD), quality of life (QoL), and pain in patients newly diagnosed with MM. Lytic bone disease was assessed, and exercise was adjusted accordingly. Primary outcome: knee extension strength. Secondary outcomes: Six-Minute-Walk-Test, 30-s Sit-to-Stand-Test (SST), grip strength, level of physical activity, LBM, BMD, QoL, and pain. Measurements were conducted pre- and post-intervention, and after 6 and 12 months. We included 100 patients, 86 were evaluable; 44 in the intervention group (IG) and 42 in the control group (CG). No statistically significant differences between groups were observed. Knee extension strength declined in the IG (p = .02). SST, aerobic capacity, and global QoL improved in both groups. Pain decreased consistently in the IG regardless of pain outcome. No significant safety concerns of physical exercise in newly diagnosed patients with MM were observed.

Symptomatic uncomplicated gallstone disease is associated with a high short-term risk of gallstone-related complications: a contemporary cohort study.

BACKGROUND: The natural history of symptomatic uncomplicated gallstone disease is largely unknown. We examined the risk of progressing from symptomatic uncomplicated to complicated gallstone disease in a large regional cohort of patients, where disruptions in elective surgical capacities have led to the indefinite postponement of surgery for benign conditions, including cholecystectomies. METHODS: Patients with radiologically diagnosed incident symptomatic and uncomplicated gallstone disease were identified from outpatient clinics and emergency departments on the Island of Funen, Denmark. The absolute risk of complications (cholecystitis, cholangitis, pancreatitis, acute cholecystectomy for unremitting pain) was calculated using death and elective cholecystectomies as competing risks using the Aalen-Johansen method. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) of gallstone complications associated with patient and gallstone characteristics. RESULTS: Two hundred eighty-six patients diagnosed with incident symptomatic, uncomplicated gallstone disease from 1 January 2020 to 1 July 2023 were identified. During 79,170 person-years of observation, 176 (61.5%) patients developed a gallstone-related complication. The 6-, 12- and 24-month risk of developing gallstone-related complications were 36%, 55% and 81%. The risk of developing complications related to common bile duct stones was lowest with larger stones (aHR per millimeter increase = 0.89 (0.82-0.97), p < 0.01), while no covariates were statistically significantly associated with the risk of cholecystitis. Eighty-five (30%) patients underwent elective laparoscopic cholecystectomy, with one patient (1.2%) developing a gallstone-related complication afterward. CONCLUSIONS: The risk of developing complications to symptomatic gallstones in a general Scandinavian population is high, and prophylactic cholecystectomy should be considered.

Poly-ϵ-caprolactone scaffold as staple-line reinforcement of rectal anastomosis: an experimental piglet study.

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.

Health-Related Quality of Life in Danish Cancer Survivors Referred to a Late Effects Clinic: A Prospective Cohort Study.

PURPOSE: The Region of Southern Denmark has recently established four late effects clinics to help cancer survivors suffering from complex and severe late effects. This study aimed to capture and analyze the full range of physical, mental, and psychosocial issues using patient-reported outcomes. Moreover, we aimed to describe demographic data and the type and severity of the late effects. METHODS: A prospective cohort study was conducted among cancer survivors referred to a late effects clinic. Before their first appointment, patients completed the European Organization for Research and Treatment of Cancer Quality of Life cancer survivorship core questionnaire (EORTC QLQ-SURV100). We compared mean scores of the EORTC QLQ-SURV100 scales that were comparable to the scales/items from the EORTC QLQ-C30 questionnaire with norm data for the Danish population and EORTC reference values. RESULTS: All patients referred to the clinic within its first 2 years were included (n = 247). The mean age was 57 [23-85] years and 74% were females. The most common cancer diagnoses was breast cancer (39%). The five most commonly reported late effects were fatigue (66%), pain (51%), cognitive impairment (53%), sleep problems (42%), and neuropathy (40%). A total of 236 of the patients entering the clinic completed QLQ-SURV100. They reported significantly worse mean scores on all scales compared to the Danish norm population and EORTC reference values for pretreatment cancer patients, p < 0.001. Effect sizes were moderate or large for all scales. INTERPRETATION: In this study, we collected demographic data and described the late effects presented by the patents referred to the clinic. Moreover, we captured and analyzed the full range of physical, mental, and psychosocial issues using QLQ-SURV100. Patients referred to the Late Effects Clinic (LEC) had a number of late effects and reported a significantly lower health-related quality of life compared to the general Danish population and patients who have just been diagnosed with cancer, suggesting the aim of helping patients suffering from late effects gain a better quality of life is in dire need.

Reaching the steady state: 30 years of Anguillicola crassus infection of European eel, Anguilla anguilla L., in Northern Germany.

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 (1991­2000), and significantly decreased in both marine and freshwater eel populations in the following decades (2001­2010, 2011­2020). 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 parasite­host relationship developed in the 30 years of interaction after the first invasion. Possible reasons and mechanisms for the observed trends in parasite­host interactions are discussed.

Mineral supplementation for very preterm infants fed fortified human milk.

OBJECTIVES: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. METHODS: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. RESULTS: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). CONCLUSIONS: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

Early-life exposure to perfluoroalkyl substances and serum antibody concentrations towards common childhood vaccines in 18-month-old children in the Odense Child Cohort.

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with reduced antibody response to childhood vaccinations. Previous studies have mostly focused on antibodies against diphtheria or tetanus, while fewer studies have assessed antibodies toward attenuated viruses, such as measles, mumps or rubella (MMR). Therefore, we set out to determine associations between prenatal and early postnatal PFAS exposure and vaccine-specific Immunoglobulin G (IgG) in the background-exposed Odense Child Cohort. Blood samples were drawn in pregnancy at gestation weeks 8-16 and from the offspring at age 18 months. In the maternal serum samples we quantified perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA). In the offspring serum samples we quantified the same five PFAS compounds and IgG towards diphtheria, tetanus and MMR. A total of 880 and 841 children were included in the analyses of diphtheria and tetanus or MMR, respectively. Multiple linear regression models were used for estimation of difference in virus-specific IgG per doubling of PFAS concentrations. Maternal PFAS concentrations were non-significantly inversely associated with most vaccine-specific antibody concentrations. Likewise, child PFAS concentrations were associated with non-significant reductions of antibodies towards tetanus and MMR. A significant reduction in the percent difference in mumps antibody concentration per doubling of child PFNA (-9.2% (95% confidence interval: -17.4;-0.2)), PFHxS (-8.3% (-15.0;-1.0) and PFOS (-7.9% (-14.8;-0.4) was found. These findings are of public health concern, as inadequate response towards childhood vaccines may represent a more general immune dysfunction.

Relationship between reasons for intermittent missing patient-reported outcomes data and missing data mechanisms.

PURPOSE: Non-response (NR) to patient-reported outcome (PRO) questionnaires may cause bias if not handled appropriately. Collecting reasons for NR is recommended, but how reasons for NR are related to missing data mechanisms remains unexplored. We aimed to explore this relationship for intermittent NRs. METHODS: Patients with multiple myeloma completed validated PRO questionnaires at enrolment and 12 follow-up time-points. NR was defined as non-completion of a follow-up assessment within seven days, which triggered contact with the patient, recording the reason for missingness and an invitation to complete the questionnaire (denoted "salvage response"). Mean differences between salvage and previous on-time scores were estimated for groups defined by reasons for NR using linear regression with clustered standard errors. Statistically significant mean differences larger than minimal important difference thresholds were interpreted as "missing not at random" (MNAR) mechanism (i.e. assumed to be related to declining health), and the remainder interpreted as aligned with "missing completely at random" (MCAR) mechanism (i.e. assumed unrelated to changes in health). RESULTS: Most (7228/7534 (96%)) follow-up questionnaires were completed; 11% (802/7534) were salvage responses. Mean salvage scores were compared to previous on-time scores by reason: those due to hospital admission, mental or physical reasons were worse in 10/22 PRO domains; those due to technical difficulties/procedural errors were no different in 21/22 PRO domains; and those due to overlooked/forgotten or other/unspecified reasons were no different in any domains. CONCLUSION: Intermittent NRs due to hospital admission, mental or physical reasons were aligned with MNAR mechanism for nearly half of PRO domains, while intermittent NRs due to technical difficulties/procedural errors or other/unspecified reasons generally were aligned with MCAR mechanism.

Kinetics of insulin and C-peptide and estimation of prehepatic insulin secretion rates after intravenous glucose stimulation using arterial versus venous blood sampling in healthy males.

An intravenous glucose-infusion of 0.3 g glucose per Kg body weight was administered over 1 min in nine healthy males with simultaneous blood sampling from the hepatic vein, femoral artery and a peripheral vein. Insulin secretion rates (ISR) were determined by the Eaton method and the ISEC method using C-peptide concentrations from arterial and peripheral venous blood. First phase (0-10 min), second phase (10-60 min), and total insulin secretion (0-60 min) were calculated as the incremental areas (iAUC) above baseline. The primary endpoint was first phase insulin response. The first phase insulin response in artery and venous blood did not differ with the Eaton method (p = 0.25), but was significantly greater with the ISEC method in arterial compared with venous blood (p < 0.05). The first phase insulin responses did not differ between methods in artery (p = 0.73) or venous blood (p = 0.73). The first phase responses of insulin and C-peptide were significant higher in the hepatic vein compared with those in the artery (p < 0.05) and peripheral vein (p < 0.05) but did not differ significantly between the artery compared with the peripheral vein for insulin (p = 0.09) or C-peptide (p = 0.26). Prehepatic insulin secretion rates did not differ between the Eaton and ISEC methods, but with the ISEC method the first phase insulin response was significantly greater in arterial compared with venous blood. The first phase insulin response differs when calculated from plasma insulin or C-peptide and depends on sample sites.

Prognostic value of 24-hour cultivation of peritoneal fluid to distinguish complicated from uncomplicated acute appendicitis: a prospective cohort study.

BACKGROUND: The distinction between complicated and uncomplicated acute appendicitis (AA) is important as it guides postoperative antibiotic treatment. A diagnosis based on intraoperative findings is imprecise and standard cultivation of peritoneal fluid is generally time-consuming with little clinical benefit. The aim of this study was to examine if cultivation of peritoneal fluid in acute appendicitis could reliably detect bacteria within 24 h. METHODS: Patients older than 18 years undergoing laparoscopic appendectomy were prospectively enrolled at two surgical departments after informed consent was obtained. Periappendicular fluid was collected prior to appendectomy and sent for cultivation. Sensitivity, specificity and positive and negative predictive values were calculated with 95% confidence intervals (CIs) using 72-hour cultivation results as the gold standard. Patients with complicated AA as determined by the surgeon, received a three-day course of oral antibiotics. Postoperative infectious complications within 30 days after surgery were registered. RESULTS: From July 2020 to January 2021, 101 patients were included. The intraoperative diagnosis was complicated AA in 34 cases. Of these patients, six (17.6%) had bacteria cultured within 24 h after surgery, leading to a sensitivity of 60% and a specificity of 100%. The positive and negative predictive values were 1.00 and 0.96, respectively. Seven patients developed a postoperative infection (five superficial wound infections and two intra-abdominal abscess). In all cases with a positive cultivation result, the intraoperative diagnosis was complicated appendicitis and a postoperative course of antibiotics prescribed. CONCLUSION: Twenty-four-hour cultivation of the peritoneal fluid in acute appendicitis is a valid indicator for peritoneal bacterial contamination. Randomized studies are necessary to determine if this approach is suitable for targeting postoperative antibiotic treatment as a means to prevent overtreatment without increasing the risk of infectious complications.

Associations of gender with sexual functioning, loneliness, depression, fatigue and physical function amongst patients suffering from rheumatoid arthritis with a particular focus on methotrexate usage.

There is a lack of knowledge regarding methotrexate (MTX) usage in patients with rheumatoid arthritis (RA) and its possible links with gender, disease characterization and sexual functioning, loneliness, fatigue and depression. We, therefore, investigated the associations of gender with physical function, fatigue, depression, loneliness and sexual functioning with a particular focus on MTX usage. A cross-sectional study design was used. Inclusion criteria were RA diagnosis, age above 18 years and available data on MTX treatment 1 year after diagnosis. Data consisted of responses from validated questionnaires regarding physical function, fatigue, depression, loneliness and sexual functioning combined with evaluations from medical records. Data were analysed with linear regression models comparing numerical outcome measures between male and female patients and between MTX users and MTX non-users. Amongst 286 patients with RA (69 men and 217 women), 67.8% were MTX users 1 year after diagnosis. Comparing women and men, both overall and within subgroups of MTX usage, we found significantly more adverse outcomes for women than men in physical functioning at diagnosis and in sexual function, depression, fatigue and physical functioning at enrolment in the study. Gender differences were also present when comparing MTX users with MTX non-users divided by gender. There were only significant differences in the HAQ and loneliness scores when comparing MTX users with MTX non-users. Women with RA had more negative outcomes measured by the selected PROMs compared to men with RA, both overall and in subgroups of users and non-users of MTX. These findings call for sharpened attention to the importance of gender in the treatment and care of patients with RA, as well as in future clinical research.

Microfibrillar-associated protein 4 as a predictive biomarker of treatment response in patients with chronic inflammatory diseases initiating biologics: secondary analyses based on the prospective BELIEVE cohort study.

BACKGROUND: Currently, there are no reliable biomarkers for predicting treatment response in chronic inflammatory diseases (CIDs). OBJECTIVE: To determine whether serum microfibrillar-associated protein 4 (MFAP4) levels can predict the treatment response to biological therapy in patients with CIDs. METHODS: The BELIEVE study was originally designed as a prospective, multi-center cohort study of 233 patients with either rheumatoid arthritis, psoriatic arthritis, psoriasis, axial spondyloarthritis, Crohn's disease, or ulcerative colitis, initiating treatment with a biologic agent (or switching to another). Clinical assessment and blood sample collection were performed at baseline and 14-16 weeks after treatment initiation. The primary analyses included participants with available blood samples at baseline; missing data were handled as non-responders. The patients were stratified into the upper tertile of serum MFAP4 (High MFAP4) versus a combined category of middle and lower tertiles (Other MFAP4). The primary outcome was the proportion of patients with clinical response to biologic therapy after 14-16 weeks. RESULTS: 211 patients were included in the primary analysis population. The mean age was 43.7 (SD: 14.8) years, and 120 (59%) were female. Positive treatment response was observed in 41 (59%) and 69 (49%) for High MFAP4 and Other MFAP4, respectively. When adjusting for pre-specified variables (CID, age, sex, smoking status, and BMI), the adjusted OR was 2.28 (95% CI: 1.07 to 4.85) for a positive treatment outcome in the High MFAP4 group. CONCLUSION: A high MFAP4 status before initiating biological treatment is associated with a positive clinical response, when adjusting for confounding factors.