Helsinki University Research Articles

Absence of orthopaedia homeobox protein (OTP) expression is associated with disease spread and adverse outcome in pulmonary carcinoid tumour patients.

Pulmonary carcinoid (PC) tumours typically have a good prognosis, although metastases occur, and the disease may progress after a long period of time. Expression of orthopaedia homeobox protein (OTP) has been recognized as a possible independent prognostic marker in PCs. Immunohistochemical (IHC) OTP expression has been associated with better prognosis, but the staining has yet to be implemented in routine clinical diagnostics. In response to this, two new monoclonal OTP antibodies were recently developed.This retrospective study included 164 PC patients operated on at Helsinki University Hospital between 1990 and 2020. Tissue microarray slides, prepared from formalin-fixed and paraffin-embedded primary tumour samples, were stained with OTP IHC using one polyclonal and two novel monoclonal antibodies.Absence of OTP expression was associated with a shorter disease-specific survival (DSS) and disease progression (p < 0.001). Patients without OTP expression had a 5-year DSS of 73-79%, whereas 5-year DSS was 91-94% with OTP expression, depending on the primary antibody. In a univariable Cox regression model, absence of OTP expression was associated with adverse outcome along with atypical histological subtype, metastatic disease, Ki-67 proliferation index > 1%, and larger tumour size. In a multivariable Cox regression model, only absence of OTP expression and lymph node involvement at the time of diagnosis were associated with risk of worse prognosis. All three antibodies showed good concordance with each other.Our findings support the role of OTP as an independent prognostic marker in PCs and applicability of IHC staining in routine clinical use with novel monoclonal antibodies.

Oral squamous cell carcinoma: Effect of tobacco and alcohol on cancer location.

The underlying factors of oral squamous cell cancers (OSCC) have been elucidated, but studies have focused little on etiological differences in affected oral cavity sites. The aim of this retrospective study was to clarify the role of carcinogen exposure in OSCC of different oral cavity areas. A cross-sectional study of patients with primary OSCC was conducted retrospectively, based on patient records from Helsinki University Hospital, Finland, between January 2016 and December 2020. The patients' self-reported history of tobacco smoking and alcohol use was explained by tumor site, age, sex, tumor size, and lymph node status in a logistic regression model. The information on smoking and alcohol use was compiled from a patient background form. In 519 patients, tumors occurred most often in the tongue (51%), gingiva (21%), or floor of the mouth (FOM; 15%). FOM had 26-fold greater odds for a history of smoking and alcohol use than other tumor sites (OR=25.78; 95% CI: 8.02-82.95; p<0.001). Gingival and buccal sites were associated significantly less with smoking and alcohol use (OR=0.43, 95% CI: 0.28-0.67; p<0.001 and OR=0.47; 95% CI: 0.25-0.92; p<0.026, respectively). Patients of older age were less likely to have a history of smoking and alcohol use (AOR=0.95; 95% CI: 0.94-0.97; p<0.001) than younger patients. Tumor size (T3-4) and FOM increased the odds for history of smoking and alcohol use (AOR=1.73; 95% CI: 1.15-2.60; p=0.009 and AOR=26.15; 95% CI: 8.01-84.84; p<0.001, respectively). OSCC of oral cavity sites has notable differences in etiology. FOM seems to be related almost exclusively to conventional smoking and heavy alcohol use.

Cognitive behavioural therapy for insomnia (CBT-I) in schizophrenia and schizoaffective disorder: protocol for a randomised controlled trial

IntroductionInsomnia is a common symptom among patients with schizophrenia and schizoaffective disorder, negatively impacting symptom severity, functioning and well-being; however, it is rarely the direct focus of treatment. The main...

Risk factors for neonatal hypoxic ischemic encephalopathy and therapeutic hypothermia: a matched case-control study

BackgroundPeripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonates, therapeutic cooling can be used to prevent or reduce permanent brain damage. The aim of this study was to assess the significance of different antenatal and delivery related risk factors for moderate and severe HIE and the need for therapeutic hypothermia.MethodsWe conducted a retrospective matched case-control study in Helsinki University area hospitals during 2013–2017. Newborn singletons with moderate or severe HIE and the need for therapeutic hypothermia were included. They were identified from the hospital database using ICD-codes P91.00, P91.01 and P91.02. For every newborn with the need for therapeutic hypothermia the consecutive term singleton newborn matched by gender, fetal presentation, delivery hospital, and the mode of delivery was selected as a control. Odds ratios (OR) between obstetric and delivery risk factors and the development of HIE were calculated.ResultsEighty-eight cases with matched controls met the inclusion criteria during the study period. Maternal and infant characteristics among cases and controls were similar, but smoking was more common among cases (aOR 1.46, CI 1.14–1.64, p = 0.003). The incidence of preeclampsia, diabetes and intrauterine growth restriction in groups was equal. Induction of labour (aOR 3.08, CI 1.18–8.05, p = 0.02) and obstetric emergencies (aOR 3.51, CI 1.28–9.60, p = 0.015) were more common in the case group. No difference was detected in the duration of the second stage of labour or the delivery analgesia.ConclusionsSmoking, induction of labour and any obstetric emergency, especially shoulder dystocia, increase the risk for HIE and need for therapeutic hypothermia. The decisions upon induction of labour need to be carefully weighed, since maternal smoking and obstetric emergencies can hardly be controlled by the clinician.

TWINGEN: protocol for an observational clinical biobank recall and biomarker cohort study to identify Finnish individuals with high risk of Alzheimer’s disease

IntroductionA better understanding of the earliest stages of Alzheimer’s disease (AD) could expedite the development or administration of treatments. Large population biobanks hold the promise to identify individuals at an...

Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial

Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed. The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed. From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%]). We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation. State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden.

Bibliometric analysis of the association between periodontal disease and cardiovascular disease

PurposeConduct a bibliometric analysis to review the knowledge structure and research trends regarding the association between periodontal disease and cardiovascular disease (CVD). MethodsThe Web of Science Core collection database was searched for retrieving publications related to periodontitis and CVD between January 1, 2003 and December 31, 2022. The VOSviewer, CiteSpace, and R software package “bibliometrix” were employed for the bibliometric analysis. ResultsIn total, 3447 articles were collected from 98 countries over the past 20 years, with the United States (1,003), Japan (377), and China (321) contributing the most publications. The literature in this field exhibited exponential growth. The University of Helsinki (n = 125, 1.37 %) holds the distinction of being the research institution with the highest number of publications, with a predominant representation from institutions in the United States. Notably, the Journal of Periodontology emerges as the most popular journal in the field, whereas the Journal of Clinical Periodontology takes the lead in terms of citations. These publications originated from 15,236 authors, with Pussinen (n = 40) having the highest number of published papers and Tonetti (n = 976) garnering the most citations. The visualization analysis of keywords identified “oral microbiome,” “inflammation,” and “porphyromonas gingivalis” as emerging research hotspots in exploring the relationship between periodontitis and CVDs. ConclusionThrough a comprehensive bibliometric analysis, this study posits that periodontitis may heighten the risk of cardiovascular events, offering valuable academic references for scholars investigating the link between periodontitis and CVDs.

90 years of Gödel’s incompleteness theorems: Logic and computation

Abstract This volume is one of two special issues collecting articles by invited speakers of the conference ‘Celebrating 90 Years of Gödel’s Incompleteness Theorems’ held in Nürtingen (Germany) in July 2021. The conference was organized by the Carl Friedrich von Weizsäcker Center at the University of Tübingen with support by the ERC-funded project Gödel Enigma: Rediscovering Kurt Gödel through his unpublished works at the University of Helsinki and by the Kurt Gödel Society in Vienna.

Stancetaking in interest-based online communities

The author defended her doctoral dissertation Stancetaking in interest-based online communities: A corpus pragmatic comparative analysis at the University of Helsinki, Faculty of Arts, on 11 November 2023. The opponent was Professor Birte Bös (Universität Duisburg-Essen) and the custos was Dr. Turo Hiltunen. The doctoral dissertation was published in the series Dissertationes Universitatis Helsingiensis. The summary of the article-based dissertation is available at http://urn.fi/URN:ISBN:978-951-51-9453-4

16-year outcomes of blunt thoracic aortic injury treated with thoracic endovascular aortic repair: A single-institution experience.

Blunt thoracic aortic injury (BTAI) is associated with considerable mortality and morbidity. Thoracic endovascular aortic repair (TEVAR) has essentially replaced open aortic repair (OAR) with superior outcome. The objective of this study was to evaluate the early and intermediate-term outcomes in patients sustaining BTAI treated with TEVAR, and to evaluate the prevalence and impact of left subclavian artery (LSA) coverage. This retrospective analysis includes patients undergoing TEVAR for BTAI between February 2006 and December 2022 at the Helsinki University Hospital, Finland. The primary endpoints were 30-day and 2-year mortality, technical success of stent-graft system deployment, and procedural and device-related complications. The secondary endpoints pertained to reintervention events: conversion to OAR, re-TEVAR, any endovascular/surgical reinterventions for optimal stent-graft function, or any reinterventions during follow-up. A total of 38 consecutive BTAI patients treated with TEVAR were included in the analyses. Median patient age was 45.5 years (range, 15-79) and 66% were male. The median follow-up period was 39 months. Technical success was 100%, 30-day mortality was 0%, and 2-year mortality was 11% in the study cohort. Coverage of LSA without revascularization (13/18) resulted in one postoperative nondisabling stroke (1/13), no paraplegia, and one had ischemic left arm findings (1/13). Only one patient required reintervention (LSA embolization; 1/38). In this institutional series, we provide further evidence in favor of TEVAR for BTAI treatment. We demonstrated that TEVAR is linked to highly favorable outcomes in the short and intermediate term, and coverage of LSA without revascularization was quite well tolerated.

&lt;i&gt;Critics Not Caretakers&lt;/i&gt;...The Public Study of Religion 20+ Years In

The topic of our conversation is Russell T. McCutcheon’s Critics Not Caretakers: Redescribing the Public Study of Religion (SUNY Press 2001). This provocative volume continues to be discussed and argued within the field, warranting an updated volume. With the release of its expanded second edition (Routledge 2024) release, the Bulletin’s editorial team thought readers would appreciate a broader conversation about the book’s impact, legacy, and potential future in framing the academic study of religion. We are joined by Leslie Smith (Avila University), Mitsutoshi Horii (Chaucer College, UK and Shumei University), Suzanne Owen (Leeds Trinity University), and Titus Hjelm (University of Helsinki) as our discussants.

Does the effect of adolescent health behaviours on adult cardiometabolic health differ by socioeconomic background? Protocol for a population-based cohort study

IntroductionAdolescence is a sensitive period for cardiometabolic health. Yet, it remains unknown if adolescent health behaviours, such as alcohol use, smoking, diet and physical activity, have differential effects across socioeconomic...

Knowledge mapping of neonatal electroencephalogram: A bibliometric analysis (2004-2022).

Electroencephalography (EEG), a widely used noninvasive neurophysiological diagnostic tool, has experienced substantial advancements from 2004 to 2022, particularly in neonatal applications. Utilizing a bibliometric methodology, this study delineates the knowledge structure and identifies emergent trends within neonatal EEG research. An exhaustive literature search was conducted on the Web of Science Core Collection (WoSCC) database to identify publications related to neonatal EEG from 2004 to 2022. Analytical tools such as VOSviewer, CiteSpace, and the R package "bibliometrix" were employed to facilitate this investigation. The search yielded 2501 articles originating from 79 countries, with the United States and England being the predominant contributors. A yearly upward trend in publications concerning neonatal EEG was observed. Notable research institutions leading this field include the University of Helsinki, University College London, and University College Cork. Clinical Neurophysiology is identified as the foremost journal in this realm, with Pediatrics as the most frequently co-cited journal. The collective body of work from 9977 authors highlights Sampsa Vanhatalo as the most prolific contributor, while Mark Steven Scher is recognized as the most frequently co-cited author. Key terms such as "seizures," "epilepsy," "hypoxic-ischemic encephalopathy," "amplitude-integrated EEG," and "brain injury" represent the focal research themes. This bibliometric analysis offers the first comprehensive review, encapsulating research trends and progress in neonatal EEG. It reveals current research frontiers and crucial directions, providing an essential resource for researchers engaged in neonatal neuroscience.

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.

A prospective cohort study: The effects of preoperative E-health on the postoperative course of tonsillectomy patients

PurposeAt our clinic, a significant portion of tonsillectomy (TE) preoperative assessments are conducted remotely. The aim of our study was to examine the variation in TE complications, contact rates, and reasons for patient contact between those evaluated preoperatively at the outpatient clinic (OPC), or remotely through virtual visits (VV), or via a digital care pathway (DCP). This investigation is critical for optimizing patient flow through the volume-intensive process of TE. MethodsWe conducted a prospective cohort study involving 422 patients who underwent TE at Helsinki University Hospital ENT clinic to investigate their 30-day postoperative course. We extracted information on postoperative contacts, complications, and demographic data. Postoperative contact rate was the primary outcome measure to evaluate whether telehealth patients suffered fewer postoperative issues. ResultsPatients from the OPC were least likely to seek medical assistance in the 30-day postoperative period. However, no significant difference was discovered compared to the remotely assessed DCP patients, and over entire TE episodes, the DCP patients had the fewest unplanned contacts compared to the VV and OPC cohorts. Furthermore, the care paths shared similar complication and contact method profiles with comparable post-tonsillectomy hemorrhage incidence. ConclusionA preoperative DCP for TE appeared to carry similar postoperative contact and complication rates, as well as comparable contact method profiles compared to the OPC model. Given the high patient satisfaction and cost-consciousness associated with the DCP, our findings encourage a broader implementation of highly developed DCPs in preoperative assessment for TE.

IGSF3 tissue expression in squamous cell carcinoma of the oropharynx: a novel tool for prognosis assessment in HPV-related and HPV-unrelated disease.

Biomarkers are not broadly used in the management of head and neck cancers (HNCs). Biomarkers have been beneficial in the management of other cancers, however, not in HNCs. Therefore, we observed the immunopositivity of a novel biomarker called immunoglobulin superfamily member 3 (IGSF3) in tumor tissues in HPV-related and HPV-unrelated OPSCC. Two patient cohorts (C1 and C2) from separate time periods were available for this study (total N = 282). Both consisted of OPSCC patients treated at the Helsinki University Hospital (HUS, Helsinki, Finland) during 2000-2016. For HPV determination, HPV mRNA in situ hybridization was used. Immunohistochemistry was used to assess IGSF3 immunopositivity in cancer tissues. Overall survival (OS) was used as endpoint in the statistical analysis. In C1, stronger immunopositivity of IGSF3 in tumor-infiltrating lymphocytes (TILs) correlated with favorable OS (p = 0.005). Stronger IGSF3 immunopositivity in tumor cells (TCs) was associated with HPV negativity (p = 0.017). Stronger IGSF3 immunopositivity in TILs correlated with HPV positivity (p < 0.001). Elevated IGSF3 immunopositivity in TILs associates with HPV-related tumors and may signify favorable prognosis. The immunopositivity of IGSF3 differs between HPV-related and HPV-unrelated OPSCC.

Changes in treatment of intracranial aneurysms during the last decade in a large European neurovascular center

ObjectiveTreatment modality for ruptured and unruptured intracranial aneurysms has shifted during the last two decades from microsurgical treatment towards endovascular treatment. We present how this transition happened in a large European neurovascular center.MethodsWe conducted a retrospective observational study consecutive patients treated for an unruptured or ruptured intracranial aneurysm at Helsinki University Hospital during 2012–2022. We used Poisson regression analysis to report age-adjusted treatment trends by aneurysm location and rupture status.ResultsA total of 2491 patients with intracranial aneurysms were treated (44% ruptured, 56% unruptured): 1421 (57%) surgically and 1070 (43%) endovascularly. A general trend towards fewer treated aneurysms was noted. The proportion of patients treated surgically decreased from 90% in 2012 to 20% in 2022. The age-adjusted decrease of surgical versus endovascular treatment was 6.9%/year for all aneurysms, 6.8% for ruptured aneurysms, and 6.8% for unruptured aneurysms. The decrease of surgical treatment was most evident in unruptured vertebrobasilar aneurysms (10.8%/year), unruptured communicating artery aneurysms (10.1%/year), ruptured communicating artery aneurysms (10.0%/year), and ruptured internal carotid aneurysms (9.0%/year). There was no change in treatment modality for middle cerebral artery aneurysms, of which 85% were still surgically treated in 2022. A trend towards an increasing size for treated ruptured aneurysms was found (p = 0.033).ConclusionA significant shift of the treatment modality from surgical to endovascular treatment occurred for all aneurysm locations except for middle cerebral artery aneurysms. Whether this shift has affected long-term safety and patient outcomes should be assessed in the future.

Mitotic abnormalities precede microsatellite instability in lynch syndrome-associated colorectal tumourigenesis

Lynch syndrome (LS) is one of the most common hereditary cancer syndromes worldwide. Dominantly inherited mutation in one of four DNA mismatch repair genes combined with somatic events leads to mismatch repair deficiency and microsatellite instability (MSI) in tumours. Due to a high lifetime risk of cancer, regular surveillance plays a key role in cancer prevention; yet the observation of frequent interval cancers points to insufficient cancer prevention by colonoscopy-based methods alone. This study aimed to identify precancerous functional changes in colonic mucosa that could facilitate the monitoring and prevention of cancer development in LS. The study material comprised colon biopsy specimens (n=71) collected during colonoscopy examinations from LS carriers (tumour-free, or diagnosed with adenoma, or diagnosed with carcinoma) and a control group, which included sporadic cases without LS or neoplasia. The majority (80%) of LS carriers had an inherited genetic MLH1 mutation. The remaining 20% included MSH2 mutation carriers (13%) and MSH6 mutation carriers (7%). The transcriptomes were first analysed with RNA-sequencing and followed up with Gorilla Ontology analysis and Reactome Knowledgebase and Ingenuity Pathway Analyses to detect functional changes that might be associated with the initiation of the neoplastic process in LS individuals. With pathway and gene ontology analyses combined with measurement of mitotic perimeters from colonic mucosa and tumours, we found an increased tendency to chromosomal instability (CIN), already present in macroscopically normal LS mucosa. Our results suggest that CIN is an earlier aberration than MSI and may be the initial cancer driving aberration, whereas MSI accelerates tumour formation. Furthermore, our results suggest that MLH1 deficiency plays a significant role in the development of CIN. The results validate our previous findings from mice and highlight early mitotic abnormalities as an important contributor and precancerous marker of colorectal tumourigenesis in LS. This work was supported by grants from the Jane and Aatos Erkko Foundation, the Academy of Finland (330606 and 331284), Cancer Foundation Finland sr, and the Sigrid Jusélius Foundation. Open access is funded by Helsinki University Library.

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

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. 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. In total 74 patients were identified; 54% were male and the mean age 45years. 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. 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.

Inflammatory and subtype-dependent serum protein signatures predict survival beyond the ctDNA in aggressive B cell lymphomas

Biological heterogeneity of large B cell lymphomas (LBCLs) is poorly captured by current prognostic tools, hampering optimal treatment decisions. We dissected the levels of 1,463 serum proteins in a uniformly treated trial cohort of 109 patients with high-risk primary LBCL (ClinicalTrials.gov: NCT01325194) and correlated the profiles with molecular data from tumor tissue and circulating tumor DNA (ctDNA) together with clinical data. We discovered clinically and biologically relevant associations beyond established clinical estimates and ctDNA. We identified an inflamed serum protein profile, which reflected host response to lymphoma, associated with inflamed and exhausted tumor microenvironment features and high ctDNA burden, and translated to poor outcome. We composed an inflammation score based on the identified inflammatory proteins and used the score to predict survival in an independent LBCL trial cohort (ClinicalTrials.gov: NCT03293173). Furthermore, joint analyses with ctDNA uncovered multiple serum proteins that correlate with tumor burden. We found that SERPINA9, TACI, and TARC complement minimally invasive subtype profiling and that TACI and TARC can be used to evaluate treatment response in a subtype-dependent manner in the liquid biopsy. Altogether, we discovered distinct serum protein landscapes that dissect the heterogeneity of LBCLs and provide agile, minimally invasive tools for precision oncology. This research was funded by grants from the Research Council of Finland, Finnish Cancer Organizations, Sigrid Juselius Foundation, University of Helsinki, iCAN Digital Precision Cancer Medicine Flagship, Orion Research Foundation sr, and Helsinki University Hospital.