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Implementation of pharmacogenetic testing in clinical care has been slow and with few exceptions is hindered by the lack of real-world evidence on how to best target testing. In this retrospective register-based study, we analyzed a nationwide cohort of 1,425,000 patients discharged from internal medicine or surgical wards and a cohort of 2,178 university hospital patients for purchases and prescriptions of pharmacogenetically actionable drugs. Pharmacogenetic variants were obtained from whole genome genotype data for a subset (n = 930) of the university hospital patients. We investigated factors associated with receiving pharmacogenetically actionable drugs and developed a literature-based cost-benefit model for pre-emptive pharmacogenetic panel testing. In a 2-year follow-up, 60.4% of the patients in the nationwide cohort purchased at least one pharmacogenetically actionable drug, most commonly ibuprofen (25.0%) and codeine (19.4%). Of the genotyped subset, 98.8% carried at least one actionable pharmacogenetic genotype and 23.3% had at least one actionable gene-drug pair. Patients suffering from musculoskeletal or cardiovascular diseases were more prone to receive pharmacogenetically actionable drugs during inpatient episode. The cost-benefit model included frequently dispensed drugs in the university hospital cohort, comprising ondansetron (19.4%), simvastatin (7.4%), clopidogrel (5.0%), warfarin (5.1%), (es)citalopram (5.3%), and azathioprine (0.5%). For untargeted pre-emptive pharmacogenetic testing of all university hospital patients, the model indicated saving €17.49 in direct healthcare system costs per patient in 2 years without accounting for the cost of the test itself. Therefore, it might be reasonable to target pre-emptive pharmacogenetic testing to patient groups most likely to receive pharmacogenetically actionable drugs., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: Preoperative risk prediction models can support shared decision-making before total hip arthroplasties (THAs). Here, we compare different machine-learning (ML) approaches to predict the six-month risk of adverse events following primary THA to obtain accurate yet simple-to-use risk prediction models., Methods: We extracted data on primary THAs (N = 262,356) between 2010 and 2018 from the Nordic Arthroplasty Register Association dataset. We benchmarked a variety of ML algorithms in terms of the area under the receiver operating characteristic curve (AUROC) for predicting the risk of revision caused by periprosthetic joint infection (PJI), dislocation or periprosthetic fracture (PPF), and death. All models were internally validated against a randomly selected test cohort (one-third of the data) that was not used for training the models., Results: The incidences of revisions because of PJI, dislocation, and PPF were 0.8%, 0.4%, and 0.3%, respectively, and the incidence of death was 1.2%. Overall, Lasso regression with stable iterative variable selection (SIVS) produced models using only four to five input variables but with AUROC comparable to more complex models using all 32 variables available. The SIVS-based Lasso models based on age, sex, preoperative diagnosis, bearing couple, fixation, and surgical approach predicted the risk of revisions caused by PJI, dislocations, and PPF, as well as death, with AUROCs of 0.61, 0.67, 0.76, and 0.86, respectively., Conclusion: Our study demonstrates that satisfactory predictive potential for adverse events following THA can be reached with parsimonious modeling strategies. The SIVS-based Lasso models may serve as simple-to-use tools for clinical risk assessment in the future., (© 2024 The Author(s). ACR Open Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Background: Prepectoral (PP) immediate implant-based breast reconstruction (IBBR) is becoming increasingly popular compared to retropectoral (RP) reconstruction. This study compares the timing of administration of different adjuvant therapy (ATs) after PP or RP IBBR., Patients and Methods: A monocentric retrospective analysis was conducted on patients undergoing mastectomy and IBBR from January 2018 to December 2023. Preoperative characteristics, mastectomy procedure type, PP or RP implant placement, postoperative outcomes, AT type, and time between surgery and AT administration were collected and analyzed., Results: 167 patients (206 breasts) were included. 123 underwent PP IBBR and 44 RP IBBR. The mean time between surgery and first AT administration was similar in the PP group (45.7 days, SD 39.3) compared to the RP group (37.4 days, SD 33.1) (p-value 0.2100). No significant differences were found in the timing of endocrine therapy (ET), chemotherapy (CT), or radiotherapy (RT) initiation between the PP and RP groups. Patients with seroma had a delayed initiation of CT (83.67 days, SD 123.7) versus those without seroma (42.1 days, SD 29.7) (p-value 0.0298)., Conclusions: The average time between surgery and administration of the first AT following PP IBBR was similar compared to RP IBBR. Postoperative seromas were associated with delayed CT in the overall population., (Copyright © 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Introduction: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell. Thus far, disease causing variants in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported highlighting the importance of characterizing gene variants in different populations for development of gene-based diagnostics and management., Methods: Whole exome sequencing was used to identify disease causing variants in Finnish PCD cohort. The effect of the identified HYDIN variants on cilia structure and function was confirmed by high-speed video analysis, immunofluorescence and electron tomography., Results: In this study, we identified three Finnish PCD patients carrying homozygous loss-of-function variants and one patient with compound heterozygous variants within HYDIN. The functional studies showed defects in the axonemal central pair complex. All patients had clinical PCD symptoms including chronic wet cough and recurrent airway infections, associated with mostly static airway cilia., Conclusion: Our results are consistent with the previously identified important role of HYDIN in the axonemal central pair complex and improve specific diagnostics of PCD in different national populations., (© 2024 The Author(s). Pediatric Pulmonology published by Wiley Periodicals LLC.)

Background: Primary prevention is the cornerstone of cardiometabolic health. In the randomized, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP), dietary counseling intervention was given to children from infancy to 20 years of age and a follow-up was completed at age 26 years. We investigated the associations of age, sex, gut microbiome, and dietary intervention with the gut metabolite and the cardiac biomarker trimethylamine-N-oxide (TMAO)., Methods: Overall, 592 healthy participants (females 46%) from STRIP were investigated. Compared to the control group, the intervention group had received dietary counseling between ages 7 months and 20 years focused on low intakes of saturated fat and cholesterol and the promotion of fruit, vegetable, and whole-grain consumption. TMAO serum concentrations were measured by a liquid chromatography-tandem mass spectrometry method at ages 11, 13, 15, 17, 19, and 26 years. Microbiome composition was assessed using 16S rRNA gene sequencing at 26 years of age., Results: TMAO concentrations increased from age 11 to 26 years in both sexes. At all measurement time points, males showed significantly higher serum TMAO concentrations compared to females, but concentrations were similar between the intervention and control groups. A direct association between TMAO concentrations and reported fiber intake was found in females. Gut microbiome analysis did not reveal associations with TMAO., Conclusions: TMAO concentration increased from childhood to early adulthood but was not affected by the given dietary intervention. In females, TMAO concentrations could be directly associated with higher fiber intake suggesting sex-specific differences in TMAO metabolism., (© Association for Diagnostics & Laboratory Medicine 2024.)

Background and Aims: Retinal microvasculature characteristics predict cardiovascular morbidity and mortality. This study investigated associations of lifelong cardiovascular risk factors and effects of dietary intervention on retinal microvasculature in young adulthood., Methods: The cohort is derived from the longitudinal Special Turku Coronary Risk Factor Intervention Project study. The Special Turku Coronary Risk Factor Intervention Project is a 20-year infancy-onset randomized controlled dietary intervention study with frequent study visits and follow-up extending to age 26 years. The dietary intervention aimed at a heart-healthy diet. Fundus photographs were taken at the 26-year follow-up, and microvascular measures [arteriolar and venular diameters, tortuosity (simple and curvature) and fractal dimensions] were derived (n = 486). Cumulative exposure as the area under the curve for cardiovascular risk factors and dietary components was determined for the longest available time period (e.g. from age 7 months to 26 years)., Results: The dietary intervention had a favourable effect on retinal microvasculature resulting in less tortuous arterioles and venules and increased arteriolar fractal dimension in the intervention group when compared with the control group. The intervention effects were found even when controlled for the cumulative cardiovascular risk factors. Reduced lifelong cumulative intake of saturated fats, main target of the intervention, was also associated with less tortuous venules. Several lifelong cumulative risk factors were independently associated with the retinal microvascular measures, e.g. cumulative systolic blood pressure with narrower arterioles., Conclusions: Infancy-onset 20-year dietary intervention had favourable effects on the retinal microvasculature in young adulthood. Several lifelong cumulative cardiovascular risk factors were independently associated with retinal microvascular structure., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Purpose: Preoperative antibiotic prophylaxis is associated to internal fixation for closed phalangeal and metacarpal fracture, but its effectiveness is not known., Methods: In a consecutive series of 119 adult patients undergoing Kirschner-wire fixation for phalangeal or metacarpal fracture, 56.3% (n = 67) received antibiotic prophylaxis and 43.7% (n = 52) did not., Results: The rate of deep surgical site infection was 1.5% (n = 1) in the group with antibiotic prophylaxis and 1.9% (n = 1) in the group without. Minor skin irritation or infection of the pin tract occurred in 13.4% of cases (n = 9) in the group with antibiotic prophylaxis and 9.6% (n = 5) in the group without., Conclusion: Our findings suggest that use of antibiotic prophylaxis could be reduced in the treatment of closed fractures of the hand treated with removable pins., Type of Study/level of Evidence: Therapeutic IV (retrospective review)., (Copyright © 2024 SFCM. Published by Elsevier Masson SAS. All rights reserved.)

Background: Prehospital anaesthesia is a complex intervention performed for critically ill patients. To minimise complications, a standard operating procedure (SOP) outlining the process is considered valuable. We investigated the implementation of an SOP for prehospital anaesthesia in helicopter emergency medical services (HEMS)., Methods: We performed a retrospective observational study of patients receiving prehospital anaesthesia by Finnish HEMS from January 2012 to August 2019. The intervention studied was the implementation of an SOP at two of the five bases during 2015-2016. Patients were stratified according to whether they were anaesthetised before, during or after implementation and the primary outcomes were 1- and 30-day mortality. Secondary outcomes included anaesthesia quality indicators. Confounding factors was assessed via logistic regression., Results: A total of 3902 tracheal intubations were performed without an SOP, 430 during implementation and 1525 after implementation. The SOP had a significant effect on 1-day mortality during implementation with an odds ratio (OR) of 0.56, 95% confidence interval (95% CI) 0.37-0.81 and a further trend towards benefit after implementation (OR 0.84, 95% CI 0.68-1.04), but no difference in 30-day mortality (OR after implementation 1.10, 95% CI 0.92-1.30). Implementation of an SOP improved first-pass success rate from 87.3% to 96.5%, p < 0.001., Conclusion: Implementation of an SOP for prehospital anaesthesia was associated with a trend towards lower 1-day mortality and an improved first-pass success but did not affect 30-day mortality. Despite this, we advocate prehospital systems to consider implementation of a prehospital anaesthesia SOP as immediate performance markers improved significantly., (© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure., Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m 2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597., Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m 2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all p interaction >0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype., Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group., Funding: Novo Nordisk., Competing Interests: Declaration of interests JD declares having received consulting honoraria from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, and Bayer, and research grants from British Heart Foundation, Medical Research Council (UK), National Institute for Health and Care Research, Public Health England, MSD, Pfizer, Aegerion, Colgate, and Roche. BMS declares having received institutional research grants to Brigham and Women's Hospital from Better Therapeutics, Merck, Novo Nordisk, and Pfizer, and consulting fees from Allergan, Boehringer Ingelheim, Better Therapeutics, Elsevier PracticeUpdate Cardiology, Esperion, Hanmi, Lexicon, Novo Nordisk, and equity in health at Scale and Doximity. SV reports speaking honoraria or consulting fees from Abbott, Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge Translation Research Group, Eli Lilly, HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, PhaseBio, and TIMI. DR declares having received consulting honoraria from Altimmune, Amgen, Biohaven, Boehringer Ingelheim, Calibrate, Carmot Therapeutics, CinRx, Eli Lilly, Epitomee, Gila Therapeutics, Ifa Celtic, Novo Nordisk, Pfizer, Rhythm, Scientific Intake, Wondr Health, and Zealand. DR also declares having received stock options from Calibrate, Epitomee, Scientific Intake, and Xeno Bioscience. IL declares having received research funding (paid to institution) from Novo Nordisk, Sanofi, Mylan, and Boehringer Ingelheim. IL received advisory or consulting fees or other support from Altimmune, AstraZeneca, Bayer, Biomea, Boehringer Ingelheim, Carmot, Cytoki Pharma, Eli Lilly, Intercept, Janssen/Johnson & Johnson, Mannkind, Mediflix, Merck, Metsera, Novo Nordisk, Pharmaventures, Pfizer, Regeneron, Sanofi, Shionogi, Structure Therapeutics, Target RWE, Terns Pharma, The Comm Group, Valeritas, WebMD, and Zealand Pharma. HMC declares being a stockholder and serving on an advisory panel for Bayer; receiving research grants from Chief Scientist Office, Diabetes UK, European Commission, IQVIA, Juvenile Diabetes Research Foundation, and Medical Research Council; serving on an advisory board and speakers bureau for Novo Nordisk; and holding stock in Roche Pharmaceuticals. SEK declares having received consulting honoraria from Anii Pharmaceuticals, Boehringer Ingelheim, Eli Lilly, Merck, Novo Nordisk, and Oramed and stock options from Altpep. JP declares having received consulting honoraria from Altimmune, Amgen, Esperion Therapeutics, Merck, MJH Life Sciences, Novartis, and Novo Nordisk; he has received a grant, paid to his institution, from Boehringer Ingelheim, and holds the position of Director, Preventive Cardiology, at Brigham and Women's Hospital. MNK declares having served as a consultant or on an advisory board for 35Pharma, Alnylam, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has received research grants from AstraZeneca, Boehringer Ingelheim, and Pfizer; holds stocks in Artera Health and Saghmos Therapeutics; and has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. MNK has also received other research support from AstraZeneca. SSE declares having received consulting honoraria from Amylyx, AstraZeneca, Avillion, Ayala, Bayer, BeiGene, Boehringer Ingelheim, 89 Bio, BioAge, BioAtla, Bristol Myers Squibb, BridgeBio, Daiichi Sankyo, Denovo, Fore Therapeutics, GlaxoSmithKline, Inovio, Insmed, Ipsen, Karuna, Lilly, Lundbeck, Mirati, Moderna, Novartis, Novavax, Novo Nordisk, National Surgical Adjuvant Breast and Bowel Project, Pfizer, Principia, Reata, Rebiotx, Roche, Sanofi, Solvd, Sutro Biopharma, and TG Therapeutics. AG declares having received honoraria from Novo Nordisk, AstraZeneca, Novartis, Boehringer Ingelheim, and Bayer. CCL declares having received consulting and research honoraria from Amarin, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Moderna, Novartis, Novo Nordisk, Pfizer, and Roche Diagnostics. MU-T declares having received consulting and research honoraria from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Frosst Laboratories, Johnson and Johnson, Menarini, Novartis, Novo Nordisk, Pfizer, Procaps, Sanofi-Aventis, Servier, and Tecnofarma. MP declares having received honoraria from Novo Nordisk. AML declares having received honoraria from Novo Nordisk, Eli Lilly, Akebia, Amgen, Ardelyx, Becton Dickson, Endologix, Fibrogen, GlaxoSmithkline, Medtronic, Neovasc, Provention Bio, ReCor, Brainstorm Cell, Alnylam, and Intarcia for consulting activities and research funding to his institution from AbbVie, Esperion, AstraZeneca, CSL Behring, Novartis, and Eli Lilly. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The aim of our study was to compare implant survival rates of different total hip arthroplasty (THA) bearings in the Nordic Arthroplasty Register Association., Methods: All conventional primary THAs performed between 2005 and 2017 in patients aged more than 55 years who had primary osteoarthritis were studied. Metal-on-highly cross-linked polyethylene (MoXLP), ceramic-on-highly cross-linked polyethylene (CoXLP), ceramic-on-ceramic (CoC), and metal-on-metal (MoM) bearings were included. The outcome was a revision. Kaplan-Meier (KM) estimates were calculated at 5 and 10 years. The risk for revision was analyzed using a flexible parametric survival model adjusted for nation, age, sex, femoral head size, and femoral fixation., Results: A total of 158,044 THAs were included. The 5-year KM estimates were 95.9% (95% confidence interval [CI] 95.8 to 96.1) in MoXLP, 95.8% (95% CI 95.6 to 96.1) in CoXLP, 96.7% (95% CI 96.4 to 97.0) in CoC, and 93.9% (95% CI 93.5 to 94.4) in MoM. The 10-years KM estimates were 94.2% (94.0 to 94.5) in MoXLP, 94.3% (93.9 to 94.8) in CoXLP, 95.4% (95.0 to 95.9) in CoC, and 85.5% (84.9 to 86.2) in MoM. Compared with MoXLP, the adjusted risk for revision was lower in CoC (hazard ratio [HR] 0.6, CI 0.5 to 0.6), similar in CoXLP (HR 1.0, CI 0.9 to 1.0), and higher in MoM (HR 1.3, CI 1.2 to 1.4)., Conclusions: We found that MoXLP, CoXLP, and CoC bearings evinced comparably high implant survival rates up to 10 years, and they can all be regarded as safe options in this patient group. The MoM bearings were associated with clearly lower survivorship. The CoC bearings had the highest implant survival and a lower adjusted risk for revision compared with highly cross-linked polyethylene bearings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Psychopathy is characterized by antisocial behavior, poor behavioral control and lacking empathy, and structural alterations in the corresponding neural circuits. Molecular brain basis of psychopathy remains poorly characterized. Here we studied type 2 dopamine receptor (D2R) and mu-opioid receptor (MOR) availability in convicted violent offenders with high psychopathic traits (n = 11) and healthy matched controls (n = 17) using positron emission tomography (PET). D2R were measured with radioligand [ 11 C]raclopride and MORs with radioligand [ 11 C]carfentanil. Psychopathic subjects had lowered D2R availability in caudate and putamen, and striatal D2R availability was also associated with degree of psychopathic traits in this prisoner sample. No group differences were found in MOR availability, although in the prisoner sample, psychopathic traits were negatively correlated with MOR availability in the amygdala and nucleus accumbens. We conclude that D2R signaling could be the putative neuromolecular pathway for psychopathy, whereas evidence for alterations in the MOR system is more limited., Competing Interests: Declaration of competing interest The authors disclose no conflict of interest, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Adolescent suicide is a major public health concern, particularly among adolescents who have endured Adverse Childhood Experiences (ACEs). Adolescents who have been exposed to multiple ACEs are as much as three times more likely to present with suicidality compared to the general adolescent population. Adolescents who have been exposed to multiple ACEs are also more likely to receive behavioral and mental health services in the community. It is therefore important to understand patterns of suicidality among this sub-population of adolescents in order to provide the best clinical care. The present study examined the temporal patterns of suicidality among adolescents who have been exposed to multiple ACEs and are receiving behavioral and mental health services in the community. Using Electronic Health Record (EHR) data from a community-based behavioral and mental health care organization, an exploratory survival analysis was conducted on time to suicidal thoughts and behaviors (STBs) after suicidality risk screen at intake. Average time from suicidality risk screen at intake to STB was 185 days (6.2 months). Youth who screened negative for suicidality risk at intake had a longer survival time than youth who screened positive for suicidality risk, and the survival distributions between the two groups was significant. Predictors of STBs were also examined, with gender being a significant predictor of an STB occurring during the follow-up period. These findings may be used to guide suicidality screening and clinical practice at community-based behavioral and mental health care organizations serving adolescents who have been exposed to multiple ACEs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Hip fracture treatment should be as standardized and effective as possible, with emphasis on fast recovery and avoidance of complications, especially those leading to reoperations. There is accumulating evidence regarding the optimal treatment of hip fractures but reports of whether this has influenced treatment in the clinical setting are sparse. The objective of this study was to determine the trends of hip fracture incidence and treatment in Finland, with special regard to how we treat older patients compared to younger ones., Materials and Methods: All operatively treated hip fractures in Finland between 1997 and 2018 were identified from a national administrative register. The incidence of these fractures and operations performed to treat them were calculated based on the adult population size., Results: Apart from a decline in the elderly age groups during the first half of the study period, the incidence of hip fractures remained relatively constant. However, the incidences of different operations changed significantly. In treatment of femoral neck fractures from 1997 to 2018, the incidence of cemented hemiarthroplasty (HA) increased from 41.1 to 59.9 per 100,000 person-years (10 5 ) and hybrid total hip arthroplasty (THA) from 0.56 to 5.93 per 10 5 , while the incidence of internal fixation (IF) decreased, for instance screw fixation from 12.5 to 2.7 per 10 5 . The incidence of cementless HA decreased from 13.3 to 1.2 per 10 5 . These changes were much more pronounced in the elderly population and there was a statistically significant difference in the proportion of patients aged > 59 treated with cemented HA and IF in 1997 compared to 2018. For trochanteric and subtrochanteric fractures, treatment with intramedullary nails replaced extramedullary devices as the most common treatment method., Conclusions: The changes in treatment methods in Finland correspond to the increasing knowledge available about the optimal treatment of hip fractures and global treatment trends., (© 2024. The Author(s).)

Background . Surgery for acute type A aortic dissection confers a risk for significant bleeding. We analyzed the impact of massive bleeding on complications after surgery for acute type A aortic dissection. Methods . Patients undergoing surgery for acute type A aortic dissection from the retrospective multicenter Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) database 2005-2014 were eligible. Massive bleeding was defined according to the Universal Definition of Perioperative Bleeding. The primary outcome measure was early mortality and secondary outcome measures were perioperative stroke, mechanical ventilation more than 48 h, new-onset dialysis, and intensive care unit stay. Propensity score matching was performed to adjust for differences in covariates. Results . Nine hundred ninety-seven patients were included, of whom 403 (40.4%) had massive bleeding. In the propensity score-matched cohort (344 pairs), patients with massive bleeding had higher 30-day mortality (17.2 versus 7.6%, p  < .001), mechanical ventilation more than 48 h (52.8 versus 22.6%, p  < .001), perioperative stroke (24.3 versus 14.8%, p  = .002), new-onset dialysis (22.5 versus 4.9%, p  < .001), and longer intensive care unit stay (6 versus 3 days, p  < .001), compared with patients without massive bleeding. Risk factors for massive bleeding were previous cardiac surgery, preoperative clopidogrel or ticagrelor therapy, DeBakey type I dissection, and localized or generalized malperfusion. Conclusions . Massive bleeding in surgery for acute type A aortic dissection is associated with a markedly increased risk for severe complications as well as early death. Further improvement of surgical technique and pharmacological optimization of coagulation is paramount to possibly improve outcomes in acute type A aortic dissection repair.

To analyze the role of interleukin IL-17A and IL-10 polymorphisms in susceptibility to juvenile idiopathic arthritis (JIA), 98 Finnish children and adolescents with JIA were studied. Data from the 1000 Genomes Project, consisting of 99 healthy Finns, served as the controls. The patients were analyzed for four IL-17A and three IL-10 gene-promoter polymorphisms, and the serum IL-17A, IL-17F, IL-10, and IL-6 levels were determined. The IL-17A rs8193036 variant genotypes (CT/CC) were more common among the patients than controls, especially in those with polyarthritis (OR 1.93, 95% CI 1.11-3.36; p = 0.020). IL-17A rs2275913 minor allele A was more common in patients (OR 1.45, 95% Cl 1.08-1.94; p = 0.014) and especially among patients with oligoarthritis and polyarthritis than the controls (OR 1.61, 95%CI 1.06-2.43; p = 0.024). Carriers of the IL-17A rs4711998 variant genotype (AG/AA) had higher serum IL-17A levels than those with genotype GG. However, carriers of the variant genotypes of IL-17A rs9395767 and rs4711998 appeared to have higher IL-17F levels than those carrying wildtype. IL-10 rs1800896 variant genotypes (TC/CC) were more abundant in patients than in the controls (OR 1.97, 95%CI 1.06-3.70; p = 0.042). Carriers of the IL-10 rs1800896 variant genotypes had lower serum levels of IL-17F than those with wildtype. These data provide preliminary evidence of the roles of IL-17 and IL-10 in the pathogenesis of JIA and its subtypes in the Finnish population. However, the results should be interpreted with caution, as the number of subjects included in this study was limited.

Competing Interests: A.V.L. receives salary support as a Medical Advisor for LifeCenter Northwest, which is not relevant to the submitted work. The remaining authors have no conflicts of interest to declare.

This study aimed to assess how parents perceived treatment-related side effects during acute lymphoblastic leukemia (ALL) treatment. Parents of children 1-17.9 years at diagnosis in Sweden, Finland, and Denmark who were alive and in first remission ≥6 months after end of ALL treatment were asked to respond on specific items regarding how their child was affected by side effects related to vincristine (VCR), corticosteroids, peg-asparaginase (ASP), and maintenance therapy, as well as overall impact of these treatments, complications in general, and their perception of impact on their child in comparison with other children with ALL. Parents of 307 children responded. More than a third reported that their child had been affected to a high extent by VCR (39.7%) and corticosteroids (35.8%), with walking difficulties, muscular weakness, pain, changes in appetite, and mood swings as the most common and severe symptoms. Reporting of these toxicities was lacking from the NOPHO ALL2008 database, except for peripheral paralysis (12.1%). For distinct toxicities reported in the NOPHO ALL2008 database, for example, thrombosis and pancreatitis, parent reports were similar to the database. Although a high overall negative impact during treatment was reported, parents generally rated the impact on their child as less, or similar, to other children with ALL. Parents perceived VCR and corticosteroid therapy, in particular, to have a negative impact on their child during ALL treatment, which was not captured in the NOPHO ALL2008 toxicity reporting. Our results highlight the importance of including patient/parent-reported outcomes in toxicity reporting., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). HemaSphere published by John Wiley & Sons Ltd on behalf of European Hematology Association.)

Background: We have earlier reported that inhaled xenon combined with hypothermia attenuates brain white matter injury in comatose survivors of out-of-hospital cardiac arrest (OHCA). A predefined secondary objective was to assess the effect of inhaled xenon on the structural changes in gray matter in comatose survivors after OHCA., Methods: Patients were randomly assigned to receive either inhaled xenon combined with target temperature management (33 °C) for 24 h (n = 55, xenon group) or target temperature management alone (n = 55, control group). A change of brain gray matter volume was assessed with a voxel-based morphometry evaluation of high-resolution structural brain magnetic resonance imaging (MRI) data with Statistical Parametric Mapping. Patients were scheduled to undergo the first MRI between 36 and 52 h and a second MRI 10 days after OHCA., Results: Of the 110 randomly assigned patients in the Xe-Hypotheca trial, 66 patients completed both MRI scans. After all imaging-based exclusions, 21 patients in the control group and 24 patients in the xenon group had both scan 1 and scan 2 available for analyses with scans that fulfilled the quality criteria. Compared with the xenon group, the control group had a significant decrease in brain gray matter volume in several clusters in the second scan compared with the first. In a between-group analysis, significant reductions were found in the right amygdala/entorhinal cortex (p = 0.025), left amygdala (p = 0.043), left middle temporal gyrus (p = 0.042), left inferior temporal gyrus (p = 0.008), left parahippocampal gyrus (p = 0.042), left temporal pole (p = 0.042), and left cerebellar cortex (p = 0.005). In the remaining gray matter areas, there were no significant changes between the groups., Conclusions: In comatose survivors of OHCA, inhaled xenon combined with targeted temperature management preserved gray matter better than hypothermia alone., Clinical Trial Registration: ClinicalTrials.gov: NCT00879892., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and Neurocritical Care Society.)

Objective: Demonstrate the utility of 3D printed temporal bone models in individual patient preoperative planning and simulation., Methods: 3D models of the temporal bone were made from 5 pediatric and adult patients at a tertiary academic hospital with challenging surgical anatomy planned for cochlear implantation or exteriorization of cholesteatoma with complex labyrinthine fistula. The 3D models were created from CT scan used for preoperative planning, simulation and intraoperative reference. The utility of models was assessed for ease of segmentation and production and impact on surgery in regard to reducing intraoperative time and costs, improving safety and efficacy., Results: Three patients received cochlear implants, two exteriorization of advanced cholesteatoma with fistulas (1 internal auditory canal/cochlea, 1 all three semicircular canals). Surgical planning and intraoperative referencing to the simulations by the attending surgeon and trainees significantly altered original surgical plans. In a case of X-linked hereditary deafness, optimal angles and rotation maneuvers for cochlear implant insertion reduced operating time by 93 min compared to the previous contralateral side surgery. Two cochlear implant cases planned for subtotal petrosectomy approach due to aberrant anatomy were successfully approached through routine mastoidectomy. The cholesteatoma cases were successfully exteriorized without necessitating partial labyrinthectomy or labyrinthine injury. There were no complications., Conclusion: 3D printed models for simulation training, surgical planning and use intraoperatively in temporal bone surgery demonstrated significant benefits in designing approaches, development of patient-specific techniques, avoidance of potential or actual complications encountered in previous or current surgery, and reduced surgical time and costs., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The improved outcome of childhood acute lymphoblastic leukemia (ALL) over the last decades has increased the importance of assessing late effects and health-related quality of life (HRQoL), particularly when evaluating and comparing outcomes in clinical trials. This study aimed to assess HRQoL in children treated for ALL according to the NOPHO ALL2008 protocol., Procedure: Children, aged 1 to less than 18 years at diagnosis, alive in first remission, and their parents, were asked to complete PedsQL 4.0 Generic Core Scales (self- and proxy-report) at ≥6 months after end of therapy. Data on socioeconomic factors and parent-reported toxicity were collected through a study-specific questionnaire, and the NOPHO ALL2008 database was used to identify eligible families and add additional disease- and treatment-related data. HRQoL data were collected during 2013-2019 in Sweden, Finland, and Denmark., Results: A total of 299 children were included. The older children (8 years and older) reported similar HRQoL scores compared to Finnish reference data, except lower scores for School Functioning in high-risk patients. Scores from the parent-proxy and self-reports from 5-7-year olds were notably lower than reference. Parent-reported toxicity was associated with lower total and physical HRQoL scores in adjusted models for younger as well as older children in the self-report and parent-proxy versions, and also with lower psychosocial score in the parent-proxy., Conclusions: Self-reported HRQoL was similar to reference population. The most important determinant for HRQoL after end of ALL treatment was parent-reported toxicity during treatment. Thus, minimizing complications is an obvious focus for future treatment protocols., (© 2024 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals LLC.)

Background: Psychosocial factors and socioeconomic status have been associated with incidence, survival, and quality of life among patients with head and neck cancer. We investigated the association between different psychosocial factors, socioeconomic status, and patient delays in T3-T4 oral, oropharyngeal, and laryngeal cancer., Patients and Methods: We conducted a nationwide prospective questionnaire-based study (n = 203) over a 3-year period., Results: We found no association between psychosocial factors (depression, social isolation, loneliness, and cynical hostility) and patient delay. Depression was three times more common among head and neck cancer patients compared with the general Finnish population. Head and neck cancer patients had lower educational levels and employment status, and were more often current smokers and heavy drinkers., Conclusions: Although we found no association between patient delay and psychosocial factors, patients diagnosed with a large head and neck cancer appeared to have a lower socioeconomic status and higher risk for developing depression, which should be considered in clinical practice., (© 2024. The Author(s).)

Background: Upper tract urothelial carcinoma (UTUC) is a rare malignancy, with typically only few new cases annually per urological department. Adherence to European association of urology (EAU) guidelines on UTUC in the Nordic countries is unknown. The objective of this survey was to examine the implementation of EAU guidelines, the perioperative management and organization of the treatment of UTUC in the Nordic countries., Methods: The electronic survey was distributed to 93 hospitals in the Nordic countries performing radical nephroureterectomy (NU). The survey consisted of 57 main questions and data was collected between December 1st, 2021 and April 23rd, 2022., Results: Overall response rate was 47/93 (67%) with a completion rate of 98%. Five out of the 6 examined subjects on diagnostic practice are applied by ≥ 72% of the participating centers. NU as treatment for high-risk UTUC is performed by 37/47 (79%), and 91% include a bladder cuff excision., Conclusions: Adherence to EAU guidelines is high on diagnostic practice in the Nordic countries, whereas disease management is less coherent., (© 2024. The Author(s).)

Background: The underlying risk factors for young-onset cryptogenic ischaemic stroke (CIS) remain unclear. This multicentre study aimed to explore the association between heavy alcohol consumption and CIS with subgroup analyses stratified by sex and age., Methods: Altogether, 540 patients aged 18-49 years (median age 41; 47.2% women) with a recent CIS and 540 sex-matched and age-matched stroke-free controls were included. Heavy alcohol consumption was defined as >7 (women) and >14 (men) units per week or at least an average of two times per month ≥5 (women) and ≥7 (men) units per instance (binge drinking). A conditional logistic regression adjusting for age, sex, education, hypertension, cardiovascular diseases, diabetes, hypercholesterolaemia, current smoking, obesity, diet and physical inactivity was used to assess the independent association between alcohol consumption and CIS., Results: Patients were twice as more often heavy alcohol users compared with controls (13.7% vs 6.7%, p<0.001), were more likely to have hypertension and they were more often current smokers, overweight and physically inactive. In the entire study population, heavy alcohol consumption was independently associated with CIS (adjusted OR 2.11; 95% CI 1.22 to 3.63). In sex-specific analysis, heavy alcohol consumption was associated with CIS in men (2.72; 95% CI 1.25 to 5.92), but not in women (1.56; 95% CI 0.71 to 3.41). When exploring the association with binge drinking alone, a significant association was shown in the entire cohort (2.43; 95% CI 1.31 to 4.53) and in men (3.36; 95% CI 1.44 to 7.84), but not in women., Conclusions: Heavy alcohol consumption, particularly binge drinking, appears to be an independent risk factor in young men with CIS., Competing Interests: Competing interests: JP: shareholder of Olvi Oyj. TT: has served/serves on scientific advisory boards for Astra Zeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Inventiva and Portola Pharm., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although knowledge of the role of the oral microbiome in ischemic stroke is steadily increasing, little is known about the multikingdom microbiota interactions and their consequences. We enrolled participants from a prospective multicentre case-control study and investigated multikingdom microbiome differences using saliva metagenomic datasets ( n  = 308) from young patients diagnosed with cryptogenic ischemic stroke (CIS) and age- and sex-matched stroke-free controls. Differentially abundant taxa were identified using Analysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC2). Functional potential was inferred using HUMANn3. Our findings revealed significant differences in the composition and functional capacity of the oral microbiota associated with CIS. We identified 51 microbial species, including 47 bacterial, 3 viral, and one fungal species associated with CIS in the adjusted model. Co-abundance network analysis highlighted a more intricate microbial network in CIS patients, indicating potential interactions and co-occurrence patterns among microbial species across kingdoms. The results of our metagenomic analysis reflect the complexity of the oral microbiome, with high diversity and multikingdom interactions, which may play a role in health and disease., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Purpose: Out-of-hospital cardiac arrest (OHCA) carries a relatively poor prognosis and requires multimodal prognostication to guide clinical decisions. Identification of previously unrecognized metabolic routes associated with patient outcome may contribute to future biomarker discovery. In OHCA, inhaled xenon elicits neuro- and cardioprotection. However, the metabolic effects remain unknown., Materials and Methods: In this post-hoc study of the randomised, 2-group, single-blind, phase 2 Xe-Hypotheca trial, 110 OHCA survivors were randomised 1:1 to receive targeted temperature management (TTM) at 33°C with or without inhaled xenon during 24 h. Blood samples for nuclear magnetic resonance spectroscopy metabolic profiling were drawn upon admission, at 24 and 72 h., Results: At 24 h, increased lactate, adjusted hazard-ratio 2.25, 95% CI [1.53; 3.30], p<0.001, and decreased branched-chain amino acids (BCAA) leucine 0.64 [0.5; 0.82], p = 0.007, and valine 0.37 [0.22; 0.63], p = 0.003, associated with 6-month mortality. At 72 h, increased lactate 2.77 [1.76; 4.36], p<0.001, and alanine 2.43 [1.56; 3.78], p = 0.001, and decreased small HDL cholesterol ester content (S-HDL-CE) 0.36 [0.19; 0.68], p = 0.021, associated with mortality. No difference was observed between xenon and control groups., Conclusions: In OHCA patients receiving TTM with or without xenon, high lactate and alanine and decreased BCAAs and S-HDL-CE associated with increased mortality. It remains to be established whether current observations on BCAAs, and possibly alanine and lactate, could reflect neural damage via their roles in the metabolism of the neurotransmitter glutamate. Xenon did not significantly alter the measured metabolic profile, a potentially beneficial attribute in the context of compromised ICU patients., Trial Registration: Trial Registry number: ClinicalTrials.gov Identifier: NCT00879892., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nummela et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Female sexual dysfunction is very common, but its determinants remain under-investigated. Vasculogenic impairments are suggested to be related to female sexual dysfunction, but previous literature regarding the association is scarce. This study aims to study the association between arterial health and female sexual function in women in their 60s., Material and Methods: The sample for this cross-sectional study comprised 117 women (aged 60-64 years) who participated in the Finnish Retirement and Aging study. Arterial health was measured according to the participants' pulse wave velocity, ankle-brachial index, blood pressure, and pulse pressure. Sexual function was measured using the Female Sexual Function Index, which resulted in a total score and six sub-scores. Associations were examined using multivariable regression analyses, which were adjusted for age, relationship happiness, systemic menopausal hormone therapy and/or local estrogen, smoking, alcohol risk use, body mass index, and depressive symptoms., Results: Higher diastolic blood pressure was associated with a higher total Female Sexual Function Index score (β = 0.24, 95% confidence interval [CI] 0.07-0.41) and with higher desire (β = 0.02, 95% CI 0.01-0.04), arousal (β = 0.04, 95% CI 0.01-0.08), lubrication (β = 0.04, 95% CI 0.002-0.08), satisfaction (β = 0.03, 95% CI 0.003-0.05), and pain (β = 0.06, 95% CI 0.02-0.10) sub-scores. Also, higher ankle-brachial index was associated with higher satisfaction sub-score (β = 2.10, 95% CI 0.44-3.73) and lower pulse pressure was associated with higher orgasm sub-score (β = 0.03, 95% CI 0.0002-0.06). Other associations between ankle-brachial index and Female Sexual Function Index scores were statistically insignificant, but considering the magnitude the findings may imply clinical significance. Systolic blood pressure and pulse wave velocity were not associated with sexual function., Conclusions: This study suggested a plausible association between higher diastolic blood pressure and female sexual function, but considering clinical significance our findings suggest an association between higher ankle-brachial index and good sexual function in women in their 60s., (© 2024 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Coronary artery calcium scoring (CACS) improves management of chest pain patients. However, it is unknown whether the benefit of CACS is dependent on the clinical likelihood (CL)., Objectives: This study aims to investigate for which patients CACS has the greatest benefit when added to a CL model., Methods: Based on data from a clinical database, the CL of obstructive coronary artery disease (CAD) was calculated for 39,837 patients referred for cardiac imaging due to symptoms suggestive of obstructive CAD. Patients were categorized according to the risk factor-weighted (RF-CL) model (very low, ≤5%; low, >5 to ≤15%; moderate >15 to ≤50%; high, >50%). CL was then recalculated incorporating the CACS result (CACS-CL). Reclassification rates and the number needed to test with CACS to reclassify patients were calculated and validated in 3 independent cohorts (n = 9,635)., Results: In total, 15,358 (39%) patients were down- or upclassified after including CACS. Reclassification rates were 8%, 75%, 53%, and 30% in the very low, low, moderate, and high RF-CL categories, respectively. Reclassification to very low CACS-CL occurred in 48% of reclassified patients. The number needed to test to reclassify 1 patient from low RF-CL to very low CACS-CL was 2.1 with consistency across age, sex, and cohorts. CACS-CL correlated better to obstructive CAD prevalence than RF-CL., Conclusions: Added to an RF-CL model for obstructive CAD, CACS identifies more patients unlikely to benefit from further testing. The number needed to test with CACS to reclassify patients depends on the pretest RF-CL and is lowest in patients with low (>5% to ≤15%) likelihood of CAD., Competing Interests: Funding Support and Author Disclosures Drs Newby and Williams have received support from the British Heart Foundation (FS/ICRF/20/26002, CH/09/002, RG/16/10/32375, RE/18/5/34216). The PROMISE study was supported by grants from the National Heart, Lung, and Blood Institute (R01HL098237, R01HL098236, R01HL098305, and R01HL098235). Dr Winther has received support from the Novo Nordisk Foundation Clinical Emerging Investigator grant (NNF21OC0066981). Dr Williams has been a speaker for Canon Medical Systems, Siemens Healthineers, and Novartis. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, and neurodegeneration in the brain parenchyma. Here, we aimed to (i) assess differences in blood and imaging biomarkers used to evaluate neurodegeneration among cognitively unimpaired APOE ε4 homozygotes, heterozygotes, and non-carriers with varying risk for sporadic AD, and (ii) to determine how different cerebral pathologies (i.e., Aβ deposition, medial temporal atrophy, and cerebrovascular pathology) contribute to blood biomarker concentrations in this sample., Methods: Sixty APOE ε4 homozygotes (n = 19), heterozygotes (n = 21), and non-carriers (n = 20) ranging from 60 to 75 years, were recruited in collaboration with Auria biobank (Turku, Finland). Participants underwent Aβ-PET ([ 11 C]PiB), structural brain MRI including T1-weighted and T2-FLAIR sequences, and blood sampling for measuring serum neurofilament light chain (NfL), plasma total tau (t-tau), plasma N-terminal tau fragments (NTA-tau) and plasma glial fibrillary acidic protein (GFAP). [ 11 C]PiB standardized uptake value ratio was calculated for regions typical for Aβ accumulation in AD. MRI images were analysed for regional volumes, atrophy scores, and volumes of white matter hyperintensities. Differences in biomarker levels and associations between blood and imaging biomarkers were tested using uni- and multivariable linear models (unadjusted and adjusted for age and sex)., Results: Serum NfL concentration was increased in APOE ε4 homozygotes compared with non-carriers (mean 21.4 pg/ml (SD 9.5) vs. 15.5 pg/ml (3.8), p = 0.013), whereas other blood biomarkers did not differ between the groups (p > 0.077 for all). From imaging biomarkers, hippocampal volume was significantly decreased in APOE ε4 homozygotes compared with non-carriers (6.71 ml (0.86) vs. 7.2 ml (0.7), p = 0.029). In the whole sample, blood biomarker levels were differently predicted by the three measured cerebral pathologies; serum NfL concentration was associated with cerebrovascular pathology and medial temporal atrophy, while plasma NTA-tau associated with medial temporal atrophy. Plasma GFAP showed significant association with both medial temporal atrophy and Aβ pathology. Plasma t-tau concentration did not associate with any of the measured pathologies., Conclusions: Only increased serum NfL concentrations and decreased hippocampal volume was observed in cognitively unimpaired APOEε4 homozygotes compared to non-carriers. In the whole population the concentrations of blood biomarkers were affected in distinct ways by different pathologies., (© 2024. The Author(s).)

Background: Better cardiovascular health is associated with lower risk of various chronic diseases, but its association with multimorbidity is poorly understood. We aimed to examine whether change in cardiovascular health is associated with multimorbidity risk., Methods: The primary analysis was conducted in the Whitehall II multiwave prospective cohort study (UK) and the validation analysis in the Finnish Public Sector cohort study (Finland). Change in cardiovascular health was assessed using the American Heart Association Life's Simple 7 (LS7) and Life's Essential 8 (LE8) at baseline and re-assessments, using objective measures in Whitehall II and self-reports and pharmacy claims in the Finnish Public Sector cohort study, respectively. Multimorbidity was defined as the presence of two or more of 12 chronic diseases during follow-up. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox's proportional hazard models with age as time scale, adjusting for sex, education, occupation, marital status, and ethnicity., Findings: In the primary analysis among 9715 participants, mean age was 44.8 (standard deviation 6.0) years and 67.6% participants were men at baseline. During the median follow-up of 31.4 (interquartile range 26.8-32.3) years, 2751 participants developed multimorbidity. The hazard of multimorbidity decreased by 8% (HR 0.92, 95% CI 0.88-0.96) per ideal LS7 metric increment over 5 years and by 14% (HR 0.86, 95% CI 0.80-0.93) per ten points increase in LE8 score over 10 years. These findings were replicated in the validation analysis among 75,377 participants in terms of 4-year change in cardiovascular health., Interpretation: Improvement in cardiovascular health was associated with lower multimorbidity risk in two community-based cohort studies. Interventions improving cardiovascular health of the community may contribute to multimorbidity prevention., Funding: None., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Purpose: Balloon dilation of the Eustachian tube (BDET) has not been evaluated extensively in children outside of retrospective case series. The purpose of this study is to report the long-term safety and efficacy of this procedure in children with matched controls., Materials and Methods: This is a two-center retrospective matched cohort study. Children having undergone tympanostomy tube (TT) placement and adenoidectomy with recurrence of symptoms underwent BDET at an academic affiliated multi-specialty practice. Comparison was made with children receiving TT at a tertiary medical center, matching for number of prior TT, prior adenoidectomy, age, and sex. Outcome measures were risk of failure and the need for additional surgery. Kaplan-Meier survival plots were used to compare risk of failure., Results: Thirty-three Eustachian tubes were dilated in 20 patients, aged 14 months-14 years. All patients had previously undergone TT insertion and adenoidectomy. Patients undergoing BDET had normal post-operative tympanograms in 80 % of cases. Mean follow up was 6.7 years with 2 patients failing in the BDET group and 8 in the TT insertion group. Dilated patients had a significantly lower risk of failure than those who underwent TT insertion (adjusted HR: 0.18; 95 % CI: 0.04, 0.81; p = 0.03). The probability of being failure free at six years was 88 % (95 % CI: 71, 95 %) in the BDET cohort and 53 % (95 % CI: 33, 70 %) in the TT insertion cohort. There were no complications., Conclusions: BDET appears to be safe and possibly superior to TT placement in children with refractory Eustachian tube dysfunction., Level of Evidence: 2b., Competing Interests: Declaration of competing interest While this study received no financial support as indicated above, Dr. Dennis Poe is a consultant for Acclarent and Dr. Marc Dean is a consultant for Acclarent, Biosense Webster, Immertec, and Stryker., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Periodontitis is associated with an increased risk of ischemic stroke, and the risk may be particularly high among young people with unexplained stroke etiology. Thus, we investigated in a case-control study whether periodontitis or recent invasive dental treatments are associated with young-onset cryptogenic ischemic stroke (CIS). We enrolled participants from a multicenter case-control SECRETO study including adults aged 18 to 49 y presenting with an imaging-positive first-ever CIS and stroke-free age- and sex-matched controls. Thorough clinical and radiographic oral examination was performed. Furthermore, we measured serum lipopolysaccharide (LPS) and lipotechoic acid (LTA) levels. Multivariate conditional regression models were adjusted for stroke risk factors, regular dentist visits, and patent foramen ovale (PFO) status. We enrolled 146 case-control pairs (median age 41.9 y; 58.2% males). Periodontitis was diagnosed in 27.5% of CIS patients and 20.1% of controls ( P < 0.001). In the fully adjusted models, CIS was associated with high periodontal inflammation burden (odds ratio [OR], 95% confidence interval) with an OR of 10.48 (3.18-34.5) and severe periodontitis with an OR of 7.48 (1.24-44.9). Stroke severity increased with the severity of periodontitis, having an OR of 6.43 (1.87-23.0) in stage III to IV, grade C. Invasive dental treatments performed within 3 mo prestroke were associated with CIS, with an OR of 2.54 (1.01-6.39). Association between CIS and invasive dental treatments was especially strong among those with PFO showing an OR of 6.26 (1.72-40.2). LPS/LTA did not differ between CIS patients and controls but displayed an increasing trend with periodontitis severity. Periodontitis and recent invasive dental procedures were associated with CIS after controlling for multiple confounders. However, the role of bacteremia as a mediator of this risk was not confirmed., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: A. Saraste discloses fees for consultancy or lectures from Abbott, Astra Zeneca, Bayer, Novartis, and Pfizer outside the current study. Other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Obstructive sleep apnea (OSA) is associated with the progression of cardiovascular diseases, arrhythmias, and sudden cardiac death (SCD). However, the acute impacts of OSA and its consequences on heart function are not yet fully elucidated. We hypothesized that desaturation events acutely destabilize ventricular repolarization, and the presence of accompanying arousals magnifies this destabilization. Ventricular repolarization lability measures, comprising heart rate corrected QT (QTc), short-time-variability of QT (STVQT), and QT variability index (QTVI), were calculated before, during, and after 20,955 desaturations from lead II electrocardiography signals of 492 patients with suspected OSA (52% men). Variations in repolarization parameters were assessed during and after desaturations, both with and without accompanying arousals, and groupwise comparisons were performed based on desaturation duration and depth. Regression analyses were used to investigate the influence of confounding factors, comorbidities, and medications. The standard deviation (SD) of QT, mean QTc, SDQTc, and STVQT increased significantly ( P < 0.01), whereas QTVI decreased ( P < 0.01) during and after desaturations. The changes in SDQT, mean QTc, SDQTc, and QTVI were significantly amplified ( P < 0.01) in the presence of accompanying arousals. Desaturation depth was an independent predictor of increased SDQTc (β = 0.405, P < 0.01), STVQT (β = 0.151, P < 0.01), and QTVI (β = 0.009, P < 0.01) during desaturation. Desaturations cause acute changes in ventricular repolarization, with deeper desaturations and accompanying arousals independently contributing to increased ventricular repolarization lability. This may partially explain the increased risk of arrhythmias and SCD in patients with OSA, especially when the OSA phenotype includes high hypoxic load and fragmented sleep. NEW & NOTEWORTHY Nocturnal desaturations are associated with increased ventricular repolarization lability. Deeper desaturations with accompanying arousals increase the magnitude of alterations, independent of confounding factors, comorbidities, and medications. Changes associated with desaturations can partially explain the increased risk of arrhythmias and sudden cardiac death in patients with OSA, especially in patients with high hypoxic load and fragmented sleep. This highlights the importance of detailed electrocardiogram analytics for patients with OSA.

Aims: Coronary computed tomography angiography (CTA) imaging is used to diagnose patients with suspected coronary artery disease (CAD). A novel artificial intelligence-guided quantitative computed tomography ischaemia algorithm (AI-QCTischaemia) aims to identify myocardial ischaemia directly from CTA images and may be helpful to improve risk stratification. The aims were to investigate (i) the prognostic value of AI-QCTischaemia amongst symptomatic patients with suspected CAD entering diagnostic imaging with coronary CTA and (ii) the prognostic value of AI-QCTischaemia separately amongst patients with no/non-obstructive CAD (≤50% visual diameter stenosis) and obstructive CAD (>50% visual diameter stenosis)., Methods and Results: For this cohort study, AI-QCTischaemia was calculated by blinded analysts amongst patients with suspected CAD undergoing coronary CTA. The primary endpoint was the composite of death, myocardial infarction (MI), or unstable angina pectoris (uAP) (median follow-up 6.9 years). A total of 1880/2271 (83%) patients had conclusive AI-QCTischaemia result. Patients with an abnormal AI-QCTischaemia result (n = 509/1880) vs. patients with a normal AI-QCTischaemia result (n = 1371/1880) had significantly higher crude and adjusted rates of the primary endpoint [adjusted hazard ratio (HRadj) 1.96, 95% confidence interval (CI) 1.46-2.63, P < 0.001; covariates: age/sex/hypertension/diabetes/smoking/typical angina]. An abnormal AI-QCTischaemia result was associated with significantly higher crude and adjusted rates of the primary endpoint amongst patients with no/non-obstructive CAD (n = 1373/1847) (HRadj 1.81, 95% CI 1.09-3.00, P = 0.022), but not amongst those with obstructive CAD (n = 474/1847) (HRadj 1.26, 95% CI 0.75-2.12, P = 0.386) (P-interaction = 0.032)., Conclusion: Amongst patients with suspected CAD, an abnormal AI-QCTischaemia result was associated with a two-fold increased adjusted rate of long-term death, MI, or uAP. AI-QCTischaemia may be useful to improve risk stratification, especially amongst patients with no/non-obstructive CAD on coronary CTA., Competing Interests: Conflict of interest: S.B. reports research grants to the institution from Medis Medical Imaging Systems, Bangerter-Rhyner Stiftung (Basel, Switzerland), and Abbott, outside the submitted work. A.S. received consultancy fees from Astra Zeneca and Pfizer, and speaker fees from Abbott, Astra Zeneca, and Novartis. J.J.B. received speaker fees from Abbott. J.P.E. and J.K.M. are employees of and hold equity in Cleerly Inc. J.K. received consultancy fees from GE Healthcare and Synektik Pharma and speaker fees from Bayer, Lundbeck, Boehringer-Ingelheim, Pfizer, and Siemens, outside of the submitted work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The global prevalence of obesity continues to rise, contributing to an increased frequency of abdominal wall reconstruction procedures, particularly ventral hernia repairs, in individuals with elevated body mass indexes. Undertaking these operations in obese patients poses inherent challenges. This review focuses on the current literature in this area, with special attention to the impact of concomitant panniculectomy. Obese individuals undergoing abdominal wall reconstruction face elevated rates of wound healing complications and hernia recurrence. The inclusion of concurrent panniculectomy heightens the risk of surgical site occurrences but does not significantly influence hernia recurrence rates. While this combined approach can be executed in obese patients, caution is warranted, due to the higher risk of complications. Physicians should carefully balance and communicate the potential risks, especially regarding the increased likelihood of wound healing complications. Acknowledging these factors is crucial in shared decision making and ensuring optimal patient outcomes in the context of abdominal wall reconstruction and related procedures in the obese population.

Surgery for type A aortic dissection (TAAD) is associated with a high risk of early mortality. The prognostic impact of a new classification of the urgency of the procedure was evaluated in this multicenter cohort study. Data on consecutive patients who underwent surgery for acute TAAD were retrospectively collected in the multicenter, retrospective European Registry of TAAD (ERTAAD). The rates of in-hospital mortality of 3,902 consecutive patients increased along with the ERTAAD procedure urgency grades: urgent procedure 10.0%, emergency procedure grade 1 13.3%, emergency procedure grade 2 22.1%, salvage procedure grade 1 45.6%, and salvage procedure grade 2 57.1% (p <0.0001). Preoperative arterial lactate correlated with the urgency grades. Inclusion of the ERTAAD procedure urgency classification significantly improved the area under the receiver operating characteristics curves of the regression model and the integrated discrimination indexes and the net reclassification indexes. The risk of postoperative stroke/global brain ischemia, mesenteric ischemia, lower limb ischemia, dialysis, and acute heart failure increased along with the urgency grades. In conclusion, the urgency of surgical repair of acute TAAD, which seems to have a significant impact on the risk of in-hospital mortality, may be useful to improve the stratification of the operative risk of these critically ill patients. This study showed that salvage surgery for TAAD is justified because half of the patients may survive to discharge., Competing Interests: Declaration of competing interest Dr. Biancari reports financial support was provided by Sigrid Jusélius Foundation and Finnish Heart Association. The remaining authors have no competing interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program. We explored the mechanisms of resistance by analyzing postprogression biopsies, as well as cross-resistance to amivantamab. Data from 86 patients with a median age of 67 years and a median of two prior lines of treatment were analyzed. Treatment-related adverse events (TRAEs) occurred in 95% of patients. Grade ≥3 TRAEs were reported in 38% of patients and included diarrhea (22%) and rash (8%). In 17% of patients, therapy was permanently discontinued, and two patients died due to TRAEs. Women were seven times more likely to discontinue treatment than men. In the overall cohort, the objective response rate to mobocertinib was 34% (95% CI, 24-45). The response rate in treatment-naïve patients was 27% (95% CI, 8-58). The median progression-free and overall survival was 5 months (95% CI, 3.5-6.5) and 12 months (95% CI, 6.8-17.2), respectively. The intracranial response rate was limited (13%), and one-third of disease progression cases involved the brain. Mobocertinib also showed antitumor activity following EGFR Ex20-specific therapy and vice versa. Potential mechanisms of resistance to mobocertinib included amplifications in MET, PIK3CA, and NRAS. Mobocertinib demonstrated meaningful efficacy in a real-world setting but was associated with considerable gastrointestinal and cutaneous toxicity.

Objective: To investigate the association between intracranial aneurysms (IAs) and thoracic aortic diameter., Methods: This observational cohort study examined thoracic aortic diameters in patients with IA. Patients were categorized by IA size (<7 mm and ≥7 mm) and IA status (ruptured/unruptured) based on radiologic findings. We investigated the association between thoracic aortic diameter and IA size and status using binary and linear regression as univariate and multivariable analyses., Results: A total of 409 patients were included. Mean age was 60 (±11.7) years and 63% were women. Thoracic aortic diameters were greater among patients who had an IA ≥7 mm versus IA <7 mm (P < 0.05). In the univariate analysis, the diameter of the ascending aorta (odds ratio [OR], 1.07; 95% confidence interval [CI], 1.02-1.129 per 1 mm; P = 0.002), aortic arch (OR, 1.10; 95% CI, 1.04-1.15 per 1 mm; P < 0.001), and descending aorta (OR, 1.10; 95% CI, 1.03-1.16 per 1 mm; P = 0.003) were associated with IAs ≥7 mm. In the multivariable regression model, larger ascending aorta (OR, 1.09; 95% CI, 1.01-1.17 per 1 mm; P = 0.018), aortic arch (OR, 1.12; 95% CI, 1.02-1.22 per 1 mm; P = 0.013), and descending aorta (OR, 1.20; 95% CI, 1.08-1.33 per 1 mm; P < 0.001) were associated with ruptured IA., Conclusions: Greater thoracic aortic diameters are associated with a higher risk of IA being larger than 7 mm and IA rupture. Exploring the concomitant growth tendency in IA and thoracic aorta provides a basis for future considerations regarding screening and risk management., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Autism spectrum disorders (ASD) are a varying group of disorders characterized by deficiency in social interaction and restrictive patterns of behavior and interests. While there are several studies focusing on the neuro-psychiatric pathogenesis of ASD, its etiology remains unclear. The role of gut-brain-axis in ASD has been studied increasingly and a correlation between symptoms and the composition of gut microbiota has been documented in various works. Despite this, the significance of individual microbes and their function is still widely unknown. This work aims to elucidate the current knowledge of the interrelations between ASD and the gut microbiota in children based on scientific evidence., Methods: This is a systematic review done by a literature search focusing on the main findings concerning the gut microbiota composition, interventions targeting the gut microbiota, and possible mechanisms explaining the results in children aged between 2 and 18 years of age., Results: Most studies in this review found significant differences between microbial communities, while there was notable variation in results regarding diversity indices or taxonomic level abundance. The most consistent results regarding taxa differences in ASD children's gut microbiota were higher levels of Proteobacteria, Actinobacteria and Sutterella compared to controls., Conclusion: These results show that the gut microbiota of children with ASD is altered compared to one of neurotypically developed children. More research is needed to discover whether some of these features could be used as potential biomarkers for ASD and how the gut microbiota could be targeted in therapeutical interventions.Appeared originally in Acta Psychiatr Scand 2023;148:242-254., (Copyright © 2024 by the American Psychiatric Association.)

Background: Males with multiple sclerosis (MS) have a higher risk for disability progression than females, but the reasons for this are unclear., Objective: We hypothesized that potential differences in TSPO-expressing microglia between female and male MS patients could contribute to sex differences in clinical disease progression., Methods: The study cohort consisted of 102 MS patients (mean (SD) age 45.3 (9.7) years, median (IQR) disease duration 12.1 (7.0-17.2) years, 72% females, 74% relapsing-remitting MS) and 76 age- and sex-matched healthy controls. TSPO-expressing microglia were measured using the TSPO-binding radioligand [ 11 C](R)-PK11195 and brain positron emission tomography (PET). TSPO-binding was quantified as distribution volume ratio (DVR) in normal-appearing white matter (NAWM), thalamus, whole brain and cortical gray matter (cGM)., Results: Male MS patients had higher DVRs compared to female patients in the whole brain [1.22 (0.04) vs. 1.20 (0.02), p  = 0.002], NAWM [1.24 (0.06) vs. 1.21 (0.05), p  = 0.006], thalamus [1.37 (0.08) vs. 1.32 (0.02), p  = 0.008] and cGM [1.25 (0.04) vs. 1.23 (0.04), p  = 0.028]. Similarly, healthy men had higher DVRs compared to healthy women except for cGM. Of the studied subgroups, secondary progressive male MS patients had the highest DVRs in all regions, while female controls had the lowest DVRs., Conclusion: We observed higher TSPO-binding in males compared to females among people with MS and in healthy individuals. This sex-driven inherent variability in TSPO-expressing microglia may predispose male MS patients to greater likelihood of disease progression., Competing Interests: SL has received travel Honoria from Roche, and research support from the Turunmaa Duodecim society, Finnish Brain Foundation, Turku Doctoral Programme in Clinical Research and Finnish Governmental Research Funding (VTR) for Turku University Hospital. MN has received research support from the Finnish MS Foundation, Maire Taponen Foundation, the Finnish Cultural Foundation, Drug Research Doctoral Programme of University of Turku and the Research Council of Finland’s Flagship InFLAMES. AS was supported by the Emil Aaltonen foundation, the Paulo Foundation, the Orion Research Foundation sr, Finnish Governmental Research Funding (VTR) for Turku University Hospital and Research Council of Finland (#341059). JR serves as a neurology consultant for Clinical Research Services Turku (CSRT Oy). LA has received honoraria from Biogen, Roche, Genzyme, Merck Serono and Novartis, and institutional research grant support from the Research Council of Finland, Sanofi-Genzyme and Merck Serono. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Laaksonen, Saraste, Nylund, Hinz, Snellman, Rinne, Matilainen and Airas.)

Background: The knowledge on vertical human papillomavirus (HPV) transmission is limited. We aimed to determine whether HPV transmission from parents to their offspring occurs before or during birth., Methods: Altogether, 321 mothers, 134 fathers, and their 321 newborn offspring from the Finnish Family HPV study cohort were included. Parents' genital and oral brush samples and semen samples were collected for HPV testing at baseline (36 weeks of pregnancy). Oral, genital, and umbilical samples from the newborn and placenta samples were collected for HPV testing immediately after delivery. HPV risk for the newborn was calculated from the mother's and father's HPV status by using logistic regression analyses., Results: Concordances between mothers' and their newborns' HPV genotype at any site were statistically significant with HPV-6, -16, -18, -31, and -56; odds ratios (ORs) ranged from 3.41 (95% confidence interval [CI], 1.80-6.48) for HPV-16 to 634 (95% CI, 28.5-14 087) for HPV-31. Father-newborn HPV concordance was statistically significant with HPV-6 and HPV-31 (ORs, 4.89 [95% CI, 1.09-21.9] and 65.0 [95% CI, 2.92-1448], respectively)., Conclusions: The genotype-specific HPV concordance between parents and their newborn is suggestive for vertical HPV transmission. However, transmission from the father to the newborn remains more uncertain., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Immune checkpoint inhibitors (ICI) have improved survival in several cancer types. Still, most patients develop disease progression during or after treatment. We evaluated the reasons for treatment discontinuation and their effect on treatment outcomes in adult patients with advanced cancer with ICI in the first or later treatment lines in Southwest Finland between 1 January 2015 and 31 December 2021. Baseline characteristics and treatment outcomes were retrospectively obtained from the electronic medical records. There were 317 patients with 15 different cancer types, most commonly non-small cell lung cancer, melanoma, and kidney cancer, treated with ICI outside clinical trials. During follow-up, 94% of the patients had discontinued treatment. A total of 62% was due to disease progression, 17% due to immune-related adverse events (irAEs), 12% after achieving disease control or radiological response, and 9% due to poor performance status. The median progression-free survival (mPFS) was 5.4 months and the median overall survival (mOS) was 20.3 months in the whole cohort. Longer mPFS and mOS were observed in patients who discontinued ICI due to irAEs (24.3 and 49.2 months) and after disease control (49.7 months and not reached). In total, 46% of the patients who discontinued ICI after irAEs or disease control remained alive and progression-free during follow-up.

Selective tropomyosin receptor kinase (TRK) inhibitors are approved targeted therapies for patients with solid tumors harboring a neurotrophic tyrosine receptor kinase ( NTRK ) gene fusion. Country-specific estimates of NTRK gene fusion frequency, and knowledge on the characteristics of affected patients, are limited. We identified patients with histologically-confirmed papillary thyroid cancer (PTC) from Finland's Auria Biobank. TRK protein expression was determined by pan-TRK immunohistochemistry. Immuno-stained tumor samples were scored by a certified pathologist. Gene fusions and other co-occurring gene alterations were identified by next generation sequencing. Patient characteristics and vital status were determined from linked hospital electronic health records (EHRs). Patients were followed from 1 year before PTC diagnosis until death. 6/389 (1.5%) PTC patients had an NTRK gene fusion (all NTRK3 ); mean age 43.8 years (and none had comorbidities) at PTC diagnosis. Gene fusion partners were EML4 ( n = 3), ETV6 ( n = 2), and RBPMS ( n = 1). Of 3/6 patients with complete EHRs, all received radioactive iodine ablation only and were alive at end of follow-up (median observation, 9.12 years). In conclusion, NTRK gene fusion is infrequent in patients with PTC. Linkage of biobank samples to EHRs is feasible in describing the characteristics and outcomes of patients with PTC and potentially other cancer types.

Aim: This study examined the predisposing factors, clinical picture, bacterial aetiology and clinical outcomes of infants and children with bacterial meningitis (BM)., Methods: The 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., Results: We 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., Conclusion: The 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., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Importance: Although cardiovascular disease (CVD) begins in early life, the extent to which blood pressure (BP) at different life stages contributes to CVD is unclear., Objective: To determine the relative contribution of BP at different life stages across the early-life course from infancy to young adulthood with carotid intima-media thickness (IMT)., Design, Setting, and Participants: The analyses were performed in 2022 using data gathered from July 1989 through January 2018 within the Special Turku Coronary Risk Factor Intervention Project, a randomized, infancy-onset cohort of 534 participants coupled with annual BP (from age 7 months to 20 years), biennial IMT measurements (from ages 13 to 19 years), who were followed up with again at age 26 years., Exposures: BP measured from infancy (aged 7 to 13 months), preschool (2 to 5 years), childhood (6 to 12 years), adolescence (13 to 17 years), and young adulthood (18 to 26 years)., Main Outcomes and Measures: Primary outcomes were carotid IMT measured in young adulthood at age 26 years. Bayesian relevant life-course exposure models assessed the relative contribution of BP at each life stage., Results: Systolic BP at each life stage contributed to the association with young adulthood carotid IMT (infancy: relative weight, 25.3%; 95% credible interval [CrI], 3.6-45.8; preschool childhood: relative weight, 27.0%; 95% CrI, 3.3-57.1; childhood: relative weight, 18.0%; 95% CrI, 0.5-40.0; adolescence: relative weight, 13.5%; 95% CrI, 0.4-37.1; and young adulthood: relative weight, 16.2%; 95% CrI, 1.6-46.1). A 1-SD (at single life-stage) higher systolic BP accumulated across the life course was associated with a higher carotid IMT (0.02 mm; 95% CrI, 0.01-0.03). The findings for carotid IMT were replicated in the Cardiovascular Risk in Young Finns Study that assessed systolic BP from childhood and carotid IMT in adulthood (33 to 45 years)., Conclusion and Relevance: In this cohort study, a life-course approach indicated that accumulation of risk exposure to BP levels at all life stages contributed to adulthood carotid IMT. Of those, the contribution attributed to each observed life stage was approximately equal. These results support prevention efforts that achieve and maintain normal BP levels across the life course, starting in infancy.

Background: Dietary fiber is an important health-promoting component of the diet, which is fermented by the gut microbes that produce metabolites beneficial for the host's health., Objectives: We studied the associations of habitual long-term fiber intake from infancy with gut microbiota composition in young adulthood by leveraging data from the Special Turku Coronary Risk Factor Intervention Project, an infancy-onset 20-y dietary counseling study., Methods: Fiber intake was assessed annually using food diaries from infancy ≤ age 20 y. At age 26 y, the first postintervention follow-up study was conducted including food diaries and fecal sample collection (N = 357). Cumulative dietary fiber intake was assessed as the area under the curve for energy-adjusted fiber intake throughout the study (age 0-26 y). Gut microbiota was profiled using 16S ribosomal ribonucleic acid amplicon sequencing. The primary outcomes were 1) α diversity expressed as the observed richness and Shannon index, 2) β diversity using Bray-Curtis dissimilarity scores, and 3) differential abundance of each microbial taxa with respect to the cumulative energy-adjusted dietary fiber intake., Results: Higher cumulative dietary fiber intake was associated with decreased Shannon index (β = -0.019 per unit change in cumulative fiber intake, P = 0.008). Overall microbial community composition was related to the amount of fiber consumed (permutational analysis of variation R 2 = 0.005, P = 0.024). The only genus that was increased with higher cumulative fiber intake was butyrate-producing Butyrivibrio (log 2 fold-change per unit change in cumulative fiber intake 0.40, adjusted P = 0.023), whereas some other known butyrate producers such as Faecalibacterium and Subdoligranulum were decreased with higher cumulative fiber intake., Conclusions: As early-life nutritional exposures may affect the lifetime microbiota composition and disease risk, this study adds novel information on the associations of long-term dietary fiber intake with the gut microbiota. This trial was registered at clinicaltrials.gov as NCT00223600., (Copyright © 2024 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)