Coexistence of metabolic-associated fatty liver disease and autoimmune or toxic liver disease.

Fatty liver disease (FLD) affects approximately 25% of global adult population. Metabolic-associated fatty liver disease (MAFLD) is a term used to emphasize components of metabolic syndrome in FLD. MAFLD does not exclude coexistence of other liver disease, but impact of coexisting MAFLD is unclear. We investigated prevalence and characteristics of MAFLD in patients with biopsy-proven autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), or toxic liver disease. Liver histopathology and clinical data from Helsinki University Hospital district (1.7 million inhabitants) between 2009 and 2019 were collected from patients with AIH, PBC, PSC, or toxic liver disease at the time of diagnosis. MAFLD was diagnosed as macrovesicular steatosis ≥5% together with obesity, type-2 diabetes, or signs of metabolic dysregulation. Of 648 patients included, steatosis was observed in 15.6% (n = 101), of which 94.1% (n = 95) was due to MAFLD. Prevalence of coexisting MAFLD in the four liver diseases varied between 12.4 and 18.2% (P = 0.483). Fibrosis was more severe in MAFLD among patients with toxic liver disease (P = 0.01). Histopathological characteristics otherwise showed similar distribution among MAFLD and non-FLD controls. Alcohol consumption was higher in MAFLD group among patients with AIH or PBC (P < 0.05 for both). In AIH, smoking was more common in patients with coexisting MAFLD (P = 0.034). Prevalence of coexisting MAFLD in other primary liver diseases is lower than reported in general population. Histopathology of MAFLD patients did not clearly differ from non-FLD ones. Alcohol and smoking were associated with MAFLD in AIH.

Prostate MRI Was Negative-What's Next?

The primary benefit of prostate MRI in the modern diagnostic pathway for prostate cancer is that many men with elevated serum PSA can safely avoid an immediate biopsy if the MRI is nonsuspicious. It is less clear, though, how these patients should be followed thereafter. Are they to be followed the same as the general population, or do they warrant more attention because of the risk of a cancer missed on MRI? In this issue, Pylväläinen and colleagues report on incidence of clinically significant prostate cancer (csPCa) and clinically insignificant PCa (ciPCa) among patients who were referred for prostate MRI for clinical suspicion of csPCa in Helsinki but had a nonsuspicious MRI (nMRI). Compared with the general population in Finland, patients who had nMRI were approximately 3.4 times more likely to be diagnosed with csPCa and 8.2 times more likely to be diagnosed with ciPCa. Balancing the competing risks of a missed csPCa versus overdiagnosis in patients after nMRI requires integration of MRI and other risk factors, especially age and PSA density. This integration may be facilitated by multivariable models and quantitative pathology and imaging. See related article by Pylväläinen et al., p. 749.

Place of living at end-of-life according to cause of death: a comparative analysis of all decedents 70 years or older in 2009-2013 in Finland and Norway.

BACKGROUND: Time at home at end-of-life is perceived as valuable to individuals. Increasing home care is therefore often a political goal. Yet, little is known about where individuals live towards their end-of-life. Our aim was to describe where individuals reside their last 6 months of life in Finland and Norway, and how this differed by cause of death, sex, age, marital status, and income. METHODS: We used individual-leveled national registry data on all decedents aged >70 years in 2009-2013 to describe the number of days individuals spent at home, in hospital, in long-term care (LTC) and short-term care (STC) facilities. We described the place of residence for all and by causes of death: cancer, diseases of the circulatory system, disease in the respiratory system, and mental and behavioral disorders (primarily dementia). We analyzed how age, marital status (indicating informal care), and income associated with place of residence. Analyses were stratified by sex and country. RESULTS: During the last 6 months of life, decedents in Finland (n=186,017) and Norway (n=159,756) spent similar amounts of days in hospital (8 and 11 days) and in STC facilities (15 and 13 days). Finnish decedents spent more days at home (96 vs. 84 days) and fewer days in LTC facilities (64 vs. 80 days). Living arrangement differed similarly by cause of death in the two countries, e.g., decedents from cancer and mental and behavioral disorders spent 123 [113] vs. 29 [21] days at home in Finland (Norway). In both countries, for all causes of death, lower age and marital status were associated with more days at home, for both males and females. While those with higher income spent more days at home in Norway, the opposite was found in Finland. CONCLUSIONS: Older individual's living arrangements in the last 6 months of life were similar in Finland and Norway but differed by cause of death. Younger individuals and those with access to informal care spent more days at home, compared to their counterparts. With aging populations, more individuals will likely need LTC at their end of life. Policies should align with these needs when developing future health care services.

Radiological features of screening-detected and interval breast cancers and subsequent survival in Eastern Finnish women.

Interval breast cancers are diagnosed between scheduled screenings and differ in many respects from screening-detected cancers. Studies comparing the survival of patients with interval and screening-detected cancers have reported differing results. The aim of this study was to investigate the radiological and histopathological features and growth rates of screening-detected and interval breast cancers and subsequent survival. This retrospective study included 942 female patients aged 50-69 years with breast cancers treated and followed-up at Kuopio University Hospital between January 2010 and December 2016. The screening-detected and interval cancers were classified as true, minimal-signs, missed, or occult. The radiological features were assessed on mammograms by one of two specialist breast radiologists with over 15 years of experience. A χ2 test was used to examine the association between radiological and pathological variables; an unpaired t test was used to compare the growth rates of missed and minimal-signs cancers; and the Kaplan-Meier estimator was used to examine survival after screening-detected and interval cancers. Sixty occult cancers were excluded, so a total of 882 women (mean age 60.4 ± 5.5 years) were included, in whom 581 had screening-detected cancers and 301 interval cancers. Disease-specific survival, overall survival and disease-free survival were all worse after interval cancer than after screening-detected cancer (p < 0.001), with a mean follow-up period of 8.2 years. There were no statistically significant differences in survival between the subgroups of screening-detected or interval cancers. Missed interval cancers had faster growth rates (0.47% ± 0.77%/day) than missed screening-detected cancers (0.21% ± 0.11%/day). Most cancers (77.2%) occurred in low-density breasts (< 25%). The most common lesion types were masses (73.9%) and calcifications (13.4%), whereas distortions (1.8%) and asymmetries (1.7%) were the least common. Survival was worse after interval cancers than after screening-detected cancers, attributed to their more-aggressive histopathological characteristics, more nodal and distant metastases, and faster growth rates.

The brain insulin receptor gene network and associations with frailty index.

OBJECTIVE: To investigate longitudinal associations between variations in the co-expression-based brain insulin receptor polygenic risk score and frailty, as well as change in frailty across follow-up. METHODS: This longitudinal study included 1605 participants from the Helsinki Birth Cohort Study. Biologically informed expression-based polygenic risk scores for the insulin receptor gene network, which measure genetic variation in the function of the insulin receptor, were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions. Frailty was assessed in at baseline in 2001-2004, 2011-2013 and 2017-2018 by applying a deficit accumulation-based frailty index. Analyses were carried out by applying linear mixed models and logistical regression models adjusted for adult socioeconomic status, birthweight, smoking and their interactions with age. RESULTS: The FI levels of women were 1.19%-points (95% CI 0.12-2.26, P = 0.029) higher than in men. Both categorical and continuous hePRS-IR in women were associated with higher FI levels than in men at baseline (P < 0.05). In women with high hePRS-IR, the rate of change was steeper with increasing age compared to those with low or moderate hePRS-IR (P < 0.05). No associations were detected between mePRS-IR and frailty at baseline, nor between mePRS-IR and the increase in mean FI levels per year in either sex (P > 0.43). CONCLUSIONS: Higher variation in the function of the insulin receptor gene network in the hippocampus is associated with increasing frailty in women. This could potentially offer novel targets for future drug development aimed at frailty and ageing.

Complications and complaints in craniofacial fractures - Finnish national data for 20 years.

OBJECTIVE: Research on reasons for malpractice claims in oral and maxillofacial surgery is scarce. The aim of this study was to investigate the causes and prevalence of permanent harm among craniofacial fracture related malpractice claims. MATERIALS AND METHODS: A retrospective register study was designed and implemented. All patients with a complaint and a diagnosis of facial or cranial fracture were included. The main outcome was the presence of permanent harm, and the predictor variable was the cause of complaint. Chi-square test was used for estimation of statistical significance. RESULTS: Delay in correct diagnosis was the leading cause of malpractice claims (63.2%), and permanent harm was found in 23.1% of the population. 82.4% of injuries were facial fractures in total population. 65.3% (n = 98) of facial trauma were related with delayed diagnostics (p < 0.001). Permanent harm was more frequent in patients with delayed diagnosis (71.4%) than those without (60.7%, p = 0.299). CONCLUSIONS: Claims of craniofacial trauma are related with under-diagnostics, and un-diagnosed facial fracture can lead to a high rate of permanent harm. Systematic clinical evaluation and facial trauma specialist consultation is recommended to set early correct diagnosis for and improve treatment of craniofacial trauma patients.

Association between human blood metabolome and the risk of gastrointestinal tumors.

BACKGROUND: The prevalence of gastrointestinal tumors continues to be significant. To uncover promising therapeutic targets for these tumors, we rigorously executed a Mendelian randomization (MR) study to comprehensively screen the blood metabolomes for potential causal mediators of five frequently encountered gastrointestinal tumors (Liver Cancer, Colorectal Cancer, Esophageal Cancer, Gastric Cancer and Pancreatic Cancer). METHODS: We selected a comprehensive set of 137 distinct blood metabolites derived from three large-scale genome-wide association studies (GWASs) involving a total of 147827 participants of European ancestry. The gastrointestinal tumors-related data were obtained from a GWAS conducted within the Finnish study. Through meticulous MR analyses, we thoroughly assessed the associations between blood metabolites and gastrointestinal tumors. Additionally, a phenome-wide MR (Phe-MR) analysis was employed to investigate the potential on-target side effects of metabolite interventions. RESULTS: We have identified 1 blood metabolites, namely isovalerylcarnitine (ORlog10: 1.01; 95%CI, 1.01-1.02; P = 1.81×10-7), as the potential causal mediators for liver cancer. However, no potential pathogenic mediators were detected for the other four tumors. CONCLUSIONS: The current systematic MR analysis elucidated the potential role of isovalerylcarnitine as a causal mediator in the development of liver cancer. Leveraging the power of Phe-MR study facilitated the identification of potential adverse effects associated with drug targets for liver cancer prevention. Considering the weighing of pros and cons, isovalerylcarnitine emerges as a promising candidate for targeted drug interventions in the realm of liver cancer prevention.

Recent Changes in the Incidence and Characteristics of Cutaneous Squamous Cell Carcinomas in Finland from 2006 to 2020: A Retrospective Cohort Study.

Registers recording only 1 tumour per patient do not enable assessment of the real burden of cutaneous squamous cell carcinoma. To investigate recent changes in the incidence and characteristics of tumours, a retrospective 15-year patient cohort study was performed in Finland. Histopathological diagnoses of cutaneous squamous cell carcinomas diagnosed between 2016 and 2020 were obtained from the pathology database and clinical data from patient medical records and combined with previously collected data for the years 2006-2015. Altogether 1,472 patients with 2,056 tumours were identified. The crude incidence increased from 19/100,000 persons in 2006 to 42 in 2020 (p < 0.001), increasing most in people aged over 80 years. The percentage of tumours located on the trunk increased from 5.3% during the first 5-year period, 2006-2010, to 9.0% in 2016-2020. Also, the location of tumours was significantly different between men and women, as men had more tumours on the scalp and ears, and women on the lower limbs. A slight change in the tumours from poorly to well differentiated and a decrease in the invasion depth were noted between 2006 and 2020. As the burden of tumours continues to increase, more attention should be paid to their prevention.

Polycystic ovary syndrome presents as a multimorbid condition by age 50: birth cohort linkage to national register data.

OBJECTIVE: This population-based follow-up study investigated register-based disease diagnoses and medication use up till age of 50 years among women with polycystic ovary syndrome (PCOS) that were identified from a population-based birth cohort. DESIGN: Population-based longitudinal cohort study. PATIENTS: Women reporting oligo/amenorrhea and hirsutism at age 31 and/or who were diagnosed with PCOS by a physician by age 46 (n = 244) and women without PCOS symptoms or diagnosis (n = 1556) in the Northern Finland Birth Cohort 1966. MAIN OUTCOME MEASURES: National register data on diagnosed diseases (International Statistical Classification of Diseases [ICD]-8-10) and medication use (Anatomical Therapeutic Chemical) until the age of 50. RESULTS: Women with PCOS had a 26% higher risk for any registered diagnosis (risk ratio [RR]: 1.26 [1.09-1.46]) and a 24% higher risk for medication use (RR: 1.24 [1.05-1.46]) compared with non-PCOS women, even after adjusting for several confounders. Several main ICD categories were more prevalent among women with PCOS versus non-PCOS controls, eg, endocrine, metabolic, nervous system, musculoskeletal, and genitourinary diseases in addition with different symptoms and injuries. Surprisingly, even though the overall morbidity was only increased in women with PCOS with a body mass index (BMI) ≥ 25 kg/m2, there were several ICD main categories that showed higher comorbidity risk especially in women with PCOS with a BMI < 25 kg/m2. Several medications were prescribed more often to women with PCOS versus non-PCOS controls, eg, medications related to the alimentary tract and metabolism, the cardiovascular system, genitourinary system drugs and sex hormones, dermatologic and hormonal preparations, and medications to treat the musculoskeletal, nervous, and respiratory systems. CONCLUSION: Women with PCOS are burdened with multimorbidity and higher medication use, independent of BMI and other confounders. Accordingly, preventive strategies are needed to alleviate the disease burden and improve the health outcomes of women with PCOS.

Clusters of lifestyle behavioral risk factors and their associations with depressive symptoms and stress: evidence from students at a university in Finland.

BACKGROUND: No previous research of university students in Finland assessed lifestyle behavioral risk factors (BRFs), grouped students into clusters, appraised the relationships of the clusters with their mental well-being, whilst controlling for confounders. The current study undertook this task. METHODS: Students at the University of Turku (n = 1177, aged 22.96 ± 5.2 years) completed an online questionnaire that tapped information on sociodemographic variables (age, sex, income sufficiency, accommodation during the semester), four BRFs [problematic alcohol consumption, smoking, food consumption habits, moderate-to-vigorous physical activity (MVPA)], as well as depressive symptoms and stress. Two-step cluster analysis of the BRFs using log-likelihood distance measure categorized students into well-defined clusters. Two regression models appraised the associations between cluster membership and depressive symptoms and stress, controlling for sex, income sufficiency and accommodation during the semester. RESULTS: Slightly more than half the study participants (56.8%) had always/mostly sufficient income and 33% lived with parents/partner. Cluster analysis of BRFs identified three distinct student clusters, namely Cluster 1 (Healthy Group), Cluster 2 (Smokers), and Cluster 3 (Nonsmokers but Problematic Drinkers). Age, sex and MVPA were not different across the clusters, but Clusters 1 and 3 comprised significantly more respondents with always/mostly sufficient income and lived with their parents/partner during the semester. All members in Clusters 1 and 3 were non-smokers, while all Cluster 2 members comprised occasional/daily smokers. Problematic drinking was significantly different between clusters (Cluster 1 = 0%, Cluster 2 = 54%, Cluster 3 = 100%). Cluster 3 exhibited significantly healthier nutrition habits than both other clusters. Regression analysis showed: (1) males and those with sufficient income were significantly less likely to report depressive symptoms or stress; (2) those living with parents/partner were significantly less likely to experience depressive symptoms; (3) compared to Cluster 1, students in the two other clusters were significantly more likely to report higher depressive symptoms; and (4) only students in Cluster 2 were more likely to report higher stress. CONCLUSIONS: BRFs cluster together, however, such clustering is not a clear-cut, all-or-none phenomenon. Students with BRFs consistently exhibited higher levels of depressive symptoms and stress. Educational and motivational interventions should target at-risk individuals including those with insufficient income or living with roommates or alone.

Pregnancy period and early-life risk factors for inflammatory bowel disease: a Northern Finland birth cohort 1966 study.

BACKGROUND: The pathogenesis of inflammatory bowel disease (IBD) has not been fully elucidated. The aim of this study was to analyze the pregnancy period, perinatal period, and infancy period risk factors for IBD in a well-characterized birth cohort from Northern Finland. METHODS: The Northern Finland Birth Cohort 1966 (NFBC1966) population comprises mothers living in the two northernmost provinces of Finland, Oulu, and Lapland, with dates of delivery between Jan 1st and Dec 31st, 1966 (12 055 mothers, 12 058 live-born children, 96.3% of all births during 1966). IBD patients were identified using hospital registries (from 1966 to 2020) and Social Insurance Institution (SII) registry reimbursement data for IBD drugs (from 1978 to 2016). The data were analyzed by Fisher's exact test and logistic regression. RESULTS: In total, 6972 individuals provided informed consent for the use of combined SII and hospital registry data. Of those, 154 (2.1%) had IBD (113 [1.6%] had ulcerative colitis (UC), and 41 (0.6%) had Crohn's disease (CD)). According to multivariate analysis, maternal smoking > 10 cigarettes/day during pregnancy was associated with a nearly 6-fold increased risk of CD in the offspring (OR 5.78, 95% CI 1.70-17.3). Breastfeeding (OR = 0.18, 95% CI 0.08-0.44) and iron supplementation during the first year of life (OR = 0.43, 95% CI 0.21-0.89) were negatively associated with CD. CONCLUSIONS: Smoking during pregnancy was associated with the risk of CD while Breastfeeding and oral iron supplementation at infancy were negatively associated with the risk of CD later in life.

Incidence of vestibular schwannoma in Finland, 1990-2017.

BACKGROUND: An increasing trend in incidence of vestibular schwannomas (VS) has been reported, though not consistently, across populations.  Materials and methods: We obtained data from the Finnish Cancer Registry on 1,149 VS cases diagnosed in 1990-2017 with tabular data up to 2022. We calculated age-standardised incidence rates (ASR) overall, by sex, and for 10-year age groups. We analysed time trends using Poisson and joinpoint regression. RESULTS: The average ASR of VS in Finland during 1990-2017 was 8.6/1,000,000 person-years for women and 7.5/1,000,000 for men. A declining trend was found with an average annual percent change of -1.7% (95% confidence interval [CI]: -2.8%, -0.6%) for women, -2.2% (95% CI: -3.6%, -0.7%) for men, and -1.9% (95% CI: -2.9%, -1.0%) for both sexes combined. The ASR in women was 11.6/1,000,000 person-years in 1990 and it decreased to 8.2/1,000,000 by 2017. Correspondingly, the incidence in men was 7.1/1,000,000 in 1990 and decreased to 5.1/1,000,000 by 2017. Some decline in incidence over time was found in all age groups below 80 years, but the decline (2.3-3.1% per year) was statistically significant only in age groups 40-49, 50-59, and 60-69 years. In the oldest age group (80+ years), the incidence of VS increased by 16% per year. For 2018-2022, the ASR was 7.6/1,000,000 for both sexes combined, with a decline by -1.7% (95% CI: -2.3%, -1.2%) annually for the entire period 1990-2022. CONCLUSION: In contrast to the increasing incidence reported in some studies, we found a decreasing trend in VS incidence for both sexes in Finland.

Cohort study on incidence of new-onset type 2 diabetes in patients after bariatric surgery and matched controls.

BACKGROUND: Metabolic bariatric surgery the reduces risk of new-onset type 2 diabetes in individuals with obesity, but it is unclear whether the benefit varies by sex, age, or socioeconomic status. The aim was to assess the risk of new-onset type 2 diabetes after metabolic bariatric surgery in these subgroups. METHODS: The Finnish Public Sector study, a follow-up study with matched controls nested in a large employee cohort, included patients without type 2 diabetes and with a diagnosis of obesity or self-reported BMI of at least 35 kg/m2. For each patient who had laparoscopic metabolic bariatric surgery (2008-2016), two propensity-score matched controls were selected. New-onset type 2 diabetes was ascertained from linked records from national health registries. RESULTS: The study included a total of 917 patients and 1811 matched controls with obesity. New-onset type 2 diabetes was diagnosed in 15 of the patients who had metabolic bariatric surgery (4.1 per 1000 person-years) and 164 controls (20.2 per 1000 person-years). The corresponding rate ratio (RR) was 0.20 (95% c.i. 0.12 to 0.35) and the rate difference (RD) was -16.1 (-19.8 to -12.3) per 1000 person-years. The risk reduction was more marked in individuals of low socioeconomic status (RR 0.10 (0.04 to 0.26) and RD -20.6 (-25.6 to -15.5) per 1000 person-years) than in those with higher socioeconomic status (RR 0.35 (0.18 to 0.66) and RD -11.5 (-16.9 to -6.0) per 1000 person-years) (Pinteraction = 0.017). No differences were observed between sexes or age groups. CONCLUSION: Metabolic bariatric surgery was associated with a reduced risk of new-onset type 2 diabetes in men and women and in all age groups. The greatest benefit was observed in individuals of low socioeconomic status.

Metabolic bariatric surgery reduces the risk of new-onset type 2 diabetes in individuals with obesity or severe obesity. The risk of new-onset type 2 diabetes after metabolic bariatric surgery varies between socioeconomic status subgroups. In this prospective study, new-onset type 2 diabetes occurred in 1.6% of 917 patients who underwent metabolic bariatric surgery and 9.1% of 1811 propensity score-matched controls. Risk reduction was more marked in individuals of low socioeconomic status. There were no differences between sex or age groups. The reduced risk of new-onset type 2 diabetes after metabolic bariatric surgery emphasizes the need to increase access to treatment in patients with severe obesity. As the preventive effect was most pronounced in individuals of low socioeconomic status associated with both greater burden of disease and worse access to healthcare, the findings need to be taken into account in health policies to reduce health inequalities.

Previous inguinal hernia surgery does not limit the likelihood of choosing prostatectomy as primary prostate cancer therapy.

We evaluated whether previous inguinal hernia repair may affect the choice of prostate carcinoma treatment in a population-based cohort. It has been suggested that previous laparoscopic inguinal hernia repair (LIHR) could limit the subsequent possibility of performing a prostatectomy. Several small studies have suggested otherwise. The study cohort included all new prostate cancer cases in Finland 1998-2015 identified through the Finnish cancer registry. Data on the treatment of prostate cancer and surgical inguinal hernia repairs in 1998-2016 was obtained from the HILMO hospital discharge registry. After linkage, the study cohort included 7206 men. Of these, 5500 had no history of inguinal hernia, 1463 had an open hernia repair, and 193 had a minimally invasive repair (LIHR). Compared to men with no history of hernia repair, those with previous hernia repairs were more likely to undergo prostatectomy over radiation therapy as the primary treatment for prostate cancer HR 1.34 (CI 95% 1.19-1.52). The association did not depend on the method of hernia repair, HR 1.58 (CI 95% 1.15-2.18), in men with previous LIHR. The increased likelihood of choosing prostatectomy over radiation therapy concerns all type prostatectomies. Previous hernia repair is not a limiting factor when choosing treatment for prostate cancer.

Stroke incidence increases with diabetic retinopathy severity and macular edema in type 1 diabetes.

BACKGROUND: As the retina is suggested to mirror the brain, we hypothesized that diabetic retinopathy and macular edema are indicative of stroke risk in type 1 diabetes and sought to assess this association in individuals with type 1 diabetes. METHODS: We included 1,268 adult FinnDiane Study participants with type 1 diabetes (age 38.7 ± 11.8 years, 51.7% men vs. 48.3% women, and 31.5% had diabetic kidney disease), data on baseline diabetic retinopathy severity, and first stroke during our observational follow-up. Retinopathy was graded by the Early Treatment Diabetic Retinopathy Study (ETDRS) scale, and macular edema as clinically significant (CSME) or not. Strokes identified from registries were confirmed from medical files. Adjusted hazard ratios (HR) for stroke by retinopathy severity and CSME were calculated by Cox models adjusted for clinical confounders, including diabetic kidney disease. RESULTS: During median 18.0 (14.1-19.3) follow-up years, 130 strokes (96 ischemic, 34 hemorrhagic) occurred. With no-very mild (ETDRS 10-20) retinopathy as reference, the adjusted HR for stroke was 1.79 (95%CI 1.02-3.15) in non-proliferative (ETDRS 35-53), and 1.69 (1.02-2.82) in proliferative (ETDRS 61-85) retinopathy. Corresponding adjusted HR for ischemic stroke was 1.68 (0.91-3.10) in non-proliferative and 1.35 (0.77-2.36) in proliferative retinopathy. The adjusted HR for hemorrhagic stroke was 2.84 (0.66-12.28) in non-proliferative and 4.31 (1.16-16.10) in proliferative retinopathy. CSME did not increase HR for any stroke type after adjustment for clinical confounders (data not shown). CONCLUSIONS: Stroke incidence increases with the severity of diabetic retinopathy independently of comorbid conditions, including diabetic kidney disease.

National trends of surgery for benign prostatic hyperplasia in Finland.

PURPOSE: To investigate national trends of surgical treatment for benign prostatic obstruction (BPO). METHODS: The Care Register for Healthcare in Finland was used to investigate the annual numbers and types of surgical procedures, operation incidence and duration of hospital stay between 2004 and 2018 in Finland. Procedures were classified using the Nordic Medico-Statistical Committee Classification of Surgical Procedures coding. Trends in incidence were analyzed with two-sided Cochran-Armitage test. Trends in duration of hospital stay and patient age were analyzed with linear regression. RESULTS: Transurethral resection of the prostate (TURP) was the most common operation type during the study period, covering over 70% of operations for BPO. Simultaneous with the implementation of photoselective vaporization of the prostate (PVP), the incidence of TURP, minimally invasive surgical therapies, transurethral vaporization of the prostate (TUVP) and open prostatectomies decreased (p < 0.05). The mean operation incidence rate in the population between 2004 and 2018 was 263 per 100,000. The duration of hospital stay shortened (p < 0.05), and the average age of operated patients increased by 2 years (p < 0.0001). CONCLUSION: The implementation of PVP did not challenge the dominating position of TURP in Finland, but it has probably influenced the overall use of other surgical therapies, excluding transurethral incision of the prostate.  The results might suggest that the conservative treatment is accentuated, patient selection is more thorough, and surgical intervention might be placed at a later stage of BPO.

Fibrous dysplasia of the head and neck in Southern Finland: a retrospective study on clinical characteristics, diagnostics, and treatment.

PURPOSE: Fibrous dysplasia (FD) is a rare genetic disease with benign bone tumors. FD can affect one (monostotic FD) or multiple bones (polyostotic FD), with craniofacial lesions being common. Because of its rarity, there are only few clinical reports on FD in the head and neck region and its clinical characteristics remain incompletely defined. This study aimed to determine patient demographics, symptoms, diagnostics, and given treatment in patients with FD of the head and neck in a Finnish population. METHODS: A retrospective review on all patients diagnosed with or treated for FD of the head and neck at the Helsinki University Hospital during 2005-2020. RESULTS: In total 74 patients were identified; 54% were male and the mean age 45 years. Overall 95% had monostotic FD. Mandibula and maxilla were the most common anatomic sites. Majority of patients had symptoms, most commonly pain and lesion growth, and 49% had extra-skeletal symptoms. For all, diagnosis was primarily based on imaging findings, biopsies were obtained from 41%. Altogether 54 patients (73%) were managed by observation only, 20 patients (27%) received treatment; ten bisphosphonates, six surgery and four both. CONCLUSION: Although highly variable in its clinical manifestations, head and neck FD lesions are often symptomatic and impose risk for extra-skeletal complications. Treatment is often conservative but should be individually tailored. Future studies are encouraged to better define the disease characteristics and hopefully offer new treatment possibilities.

Prostate Cancer Screening With PSA, Kallikrein Panel, and MRI: The ProScreen Randomized Trial.

Importance: Prostate-specific antigen (PSA) screening has potential to reduce prostate cancer mortality but frequently detects prostate cancer that is not clinically important. Objective: To describe rates of low-grade (grade group 1) and high-grade (grade groups 2-5) prostate cancer identified among men invited to participate in a prostate cancer screening protocol consisting of a PSA test, a 4-kallikrein panel, and a magnetic resonance imaging (MRI) scan. Design, Setting, and Participants: The ProScreen trial is a clinical trial conducted in Helsinki and Tampere, Finland, that randomized 61 193 men aged 50 through 63 years who were free of prostate cancer in a 1:3 ratio to either be invited or not be invited to undergo screening for prostate cancer between February 2018 and July 2020. Interventions: Participating men randomized to the intervention underwent PSA testing. Those with a PSA level of 3.0 ng/mL or higher underwent additional testing for high-grade prostate cancer with a 4-kallikrein panel risk score. Those with a kallikrein panel score of 7.5% or higher underwent an MRI of the prostate gland, followed by targeted biopsies for those with abnormal prostate gland MRI findings. Final data collection occurred through June 31, 2023. Main Outcomes and Measures: In descriptive exploratory analyses, the cumulative incidence of low-grade and high-grade prostate cancer after the first screening round were compared between the group invited to undergo prostate cancer screening and the control group. Results: Of 60 745 eligible men (mean [SD] age, 57.2 [4.0] years), 15 201 were randomized to be invited and 45 544 were randomized not to be invited to undergo prostate cancer screening. Of 15 201 eligible males invited to undergo screening, 7744 (51%) participated. Among them, 32 low-grade prostate cancers (cumulative incidence, 0.41%) and 128 high-grade prostate cancers (cumulative incidence, 1.65%) were detected, with 1 cancer grade group result missing. Among the 7457 invited men (49%) who refused participation, 7 low-grade prostate cancers (cumulative incidence, 0.1%) and 44 high-grade prostate cancers (cumulative incidence, 0.6%) were detected, with 7 cancer grade groups missing. For the entire invited screening group, 39 low-grade prostate cancers (cumulative incidence, 0.26%) and 172 high-grade prostate cancers (cumulative incidence, 1.13%) were detected. During a median follow-up of 3.2 years, in the group not invited to undergo screening, 65 low-grade prostate cancers (cumulative incidence, 0.14%) and 282 high-grade prostate cancers (cumulative incidence, 0.62%) were detected. The risk difference for the entire group randomized to the screening invitation vs the control group was 0.11% (95% CI, 0.03%-0.20%) for low-grade and 0.51% (95% CI, 0.33%-0.70%) for high-grade cancer. Conclusions and Relevance: In this preliminary descriptive report from an ongoing randomized clinical trial, 1 additional high-grade cancer per 196 men and 1 low-grade cancer per 909 men were detected among those randomized to be invited to undergo a single prostate cancer screening intervention compared with those not invited to undergo screening. These preliminary findings from a single round of screening should be interpreted cautiously, pending results of the study's primary mortality outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT03423303.

Gut bacteriome and mood disorders in women with PCOS.

STUDY QUESTION: How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? SUMMARY ANSWER: Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. WHAT IS KNOWN ALREADY: Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. STUDY DESIGN, SIZE, DURATION: This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. MAIN RESULTS AND THE ROLE OF CHANCE: We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). LIMITATIONS, REASONS FOR CAUTION: Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. WIDER IMPLICATIONS OF THE FINDINGS: The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Circulating cytokines levels and osteoarthritis: A Mendelian randomization study.

BACKGROUND: Previous traditional observational studies have suggested the contribution of several cytokines and growth factors to the development of osteoarthritis (OA). This study aimed to determine the association of circulating cytokine and growth factor levels with OA. METHODS: We used two-sample Mendelian randomization (MR) to explore the causality between circulating cytokine and growth factor levels and OA [including knee or hip OA (K/HOA), knee OA (KOA), and hip OA (HOA)]. Summary level data for circulating cytokine and growth factor levels were sourced from a genome-wide association study (GWAS) involving 8,293 participants of Finnish ancestry. Single-nucleotide polymorphisms related to K/HOA (39,427 cases and 378,169 controls), KOA (24,955 cases and 378,169 controls), and HOA (15,704 cases and 378,169 controls) were obtained from a previous GWAS. The inverse variance weighted (IVW) method was primarily used for our MR analysis. For exposures to only one relevant SNP as IV, we used the Wald ratio as the major method to assess causal effects. We also conducted a series of sensitivity analyses to improve the robustness of the results. RESULTS: Circulating vascular endothelial growth factor levels were suggestively associated with an increased risk of K/HOA (odds ratio (OR) = 1.034; 95 % confidence interval (CI) = 1.013-1.055; P = 0.001), KOA (OR = 1.034; 95 % CI = 1.014-1.065; P = 0.002), and HOA (OR = 1.039; 95 % CI = 1.003-1.067; P = 0.034). Circulating interleukin (IL)-12p70 levels was suggestively associated with K/HOA (OR = 1.047; 95 % CI = 1.018-1.077; P = 0.001), KOA (OR = 1.058; 95 % CI = 1.022-1.095; P = 0.001), and HOA (OR = 1.044; 95 % CI = 1.000-1.091; P = 0.048). Circulating IL-18 levels were suggestively associated with HOA (OR = 1.068; 95 % CI = 1.014-1.125; P = 0.012). However, limited evidence exists to support causal genetic relationships between other circulating cytokines, growth factor levels and K/HOA, KOA, and HOA. CONCLUSIONS: Our MR analysis provides suggestive evidence of causal relationships between circulating cytokines and growth factors levels and OA, providing new insights into the etiology of OA.