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Abstract In this single‐center study, we aimed to describe the characteristics, treatment patterns, and outcomes of patients with multiple myeloma (MM) following treatment with bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide or pomalidomide‐based regimens. Data were collected retrospectively from a study cohort of patients receiving a MM treatment in the Hospital District of Helsinki and Uusimaa (HUS) in Finland between 2016–2020. In total, 472 patients were included in the study. Median age was 68.2 years and nearly 25% had a high cytogenetic risk according to the International Myeloma Working Group categorization. In 2018–2020, the spectrum of regimens used as third‐ or later‐line therapy was notably broader than in 2016–2017. The overall response rates for patients who received the most novel regimens (available ≤ 5 years) in second or third line of therapy (n = 67/430) and fourth line or later (n = 78/151) were 53.3% and 25.0%, respectively. In this real‐world MM patient cohort, the response rates for these novel agents were lower compared to those reported in clinical trials. Given the higher cytogenetic risk profile and more advanced disease stage at the time when treated with novel agents, patients could have benefited from effective novel therapies earlier in their treatment pathway. What is the NEW aspect of your work? (ONE sentence) This study characterized the treatment of Finnish multiple myeloma patients during the era of most novel therapies (after 2016) and also included information on the cytogenetic risk profile of this real‐world population. What is the CENTRAL finding of your work? (ONE sentence) There are clear differences between real‐world populations treated with most novel combinations and those of randomized controlled trials (RCTs), which is reflected by the poorer treatment outcomes in the real‐world setting. What is (or could be) the SPECIFIC clinical relevance of your work? (ONE sentence) Given the high cytogenetic risk profile and advanced disease stage at the time when treated with novel agents, patients could have benefited from effective novel therapies earlier in their treatment pathway.

Abstract Fermentation of dietary fiber by gut microbes produces short-chain fatty acids (SCFA), but fermentation outcomes are affected by dietary fiber source and microbiota composition. The aim of this study was to investigate the effect of two different fecal microbial compositions on in vitro fermentation of a standardized amount of oat, rye, and wheat breads. Two human fecal donors with different microbial community composition were recruited. Bread samples were digested enzymatically. An in vitro fermentation model was used to study SCFA production, dietary fiber degradation, pH, and changes in microbiota. Feces from donor I had high relative abundance of Bacteroides and Escherichia/Shigella, whereas feces from donor II were high in Prevotella and Subdoligranulum. Shifts in microbiota composition were observed during fermentation. SCFA levels were low in the samples with fecal microbiota from donor I after 8 h of fermentation, but after 24 h acetate and propionate levels were similar in the samples from the different donors. Butyrate levels were higher in the fermentation samples from donor II, especially with rye substrate, where high abundance of Subdoligranulum was observed. Dietary fiber degradation was also higher in the fermentation samples from donor II. In conclusion, fermentation capacity and substrate utilization differed between the two different microbiota compositions.

Taito Niemelä,1 Hannu Kankaanranta,1– 3 Iida Vähätalo,2 Juho Loponen,1,2 Leena E Tuomisto,2 Onni Niemelä,1,4 Mari Hämäläinen,5 Eeva Moilanen,5 Pinja Ilmarinen1,2 1Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 2Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; 3Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Department of Laboratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; 5The Immunopharmacology Research Group, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, FinlandCorrespondence: Pinja Ilmarinen, Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland, Tel +35 850 420 0596, Email pinja.ilmarinen@epshp.fiBackground: Soluble urokinase plasminogen activator receptor (suPAR) has emerged as a novel biomarker for various inflammatory conditions and has been proposed to associate with the severity of asthma. However, the relationship between suPAR and clinical asthma features is poorly understood.Objective: To examine associations of serum suPAR levels with clinical characteristics of asthma and to define the phenotype with high suPAR levels in patients with adult-onset asthma.Methods: Serum suPAR levels were measured with ELISA from patients with adult-onset asthma participating in the 12-year follow-up visit in the Seinäjoki Adult Asthma Study.Results: In total, 201 patients were divided into quartiles according to suPAR values. High suPAR patients had more severe asthma symptoms and poorer asthma control. They also had higher levels of interleukin 8 (IL-8), interleukin 6 (IL-6), matrix metalloproteinase 9 (MMP-9), and blood neutrophil counts than those with low suPAR levels. The use of high-dose inhaled and oral corticosteroids was more common in patients with elevated suPAR. Such patients also had visited healthcare more frequently during the follow-up period, had more comorbidities, and were physically less active than those with low suPAR levels. The above-mentioned results remained similar after excluding the patients with co-existing COPD; only association to hospitalizations was lost. In multivariable binary regression analyses, the highest suPAR quartile was associated with higher cumulative dispensed oral corticosteroid use, more severe symptoms, and uncontrolled asthma.Conclusion: High suPAR levels occur in uncontrolled adult-onset asthma patients characterized by neutrophilic inflammation, high corticosteroid use, frequent healthcare visits, and multimorbidity with unhealthy lifestyle. This biomarker could be useful in determining asthma phenotypes and target new asthma treatments.Keywords: asthma, adult-onset, neutrophil, phenotypes, suPAR, uncontrolled

Abstract Objectives We conducted this retrospective study to characterize the change in chronic lymphocytic leukemia (CLL) treatment patterns between 2005 and 2019, to understand the treatment sequencing across the course of the disease, and to investigate how targeted agents and prognostic testing were implemented into the patient care. Methods This study included adult patients with CLL treated at the Hospital District of Southwest Finland during the study period. Data were collected from the Turku University Hospital data lake. Results In total, 122 and 60 patients received first‐ and second‐line treatments for CLL, respectively. The shift from conventional chemoimmunotherapy to targeted treatments in recent years (2014–2019) was observed. The median overall survival times were not reached in patients treated with targeted agents compared to conventional standard treatments in first‐ and second‐line settings and improved toward the end of the study period. Prognostic testing increased during the study follow‐up and patients with unmutated immunoglobulin heavy‐chain variable showed significantly poorer overall survival and time‐to‐next‐treatment outcomes than patients with mutated immunoglobulin heavy‐chain variable. Conclusions This real‐world study implicated added value of targeted chemo‐free therapies as reported in randomized clinical trials, and highlighted the necessity of prognostic testing in order to improve treatment selection and patient outcomes.

Abstract Background A low intake of Fermentable, Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs) is effective in the symptom control of irritable bowel syndrome (IBS) patients but may exert negative effects on the intestinal microbiota. The microbial effects of increasing regular or non-FODMAP fibre sources are largely unknown. Furthermore, it is not known if the baseline microbiota composition is associated with individual symptom control during the consumption of different rye products in IBS patients. Our objective was to evaluate whether increased consumption of low-FODMAP rye bread or regular rye bread for 4 weeks would alter the intestinal microbiota composition of IBS patients following their habitual diet, and whether these changes associate to symptoms and/or the baseline microbiota. Methods The study was conducted as a randomized double blind controlled cross-over study (n = 50). Microbiota was analysed by 16S rRNA gene sequencing and associated with gastrointestinal symptoms. Both microbial changes and their associations to symptoms were secondary outcomes. Results The consumption of the test breads did not alter microbiota diversity. Compared to baseline, consumption of the low FODMAP rye bread decreased the abundance of Bacteroides, Flavonifractor, Holdemania, Parasutterella and Klebsiella and showed a trend towards increased bifidobacteria, whereas the regular rye bread decreased the abundance of Flavonifractor. When comparing between the two test breads, Klebsiella was decreased after low-FODMAP rye bread intake. Patients whose symptoms decreased during the low-FODMAP rye bread displayed more Blautia and less Barnesiella at baseline. Conclusions Consumption of low-FODMAP rye bread had modest, potentially beneficial effects on patients’ microbiota while increasing their intake of fibre substantially. The baseline microbiota composition was associated with the variable degrees of symptom relief experienced by the patients. Consumption of a low-FODMAP rye bread might be one way to increase dietary fibre intake and improve the mild dysbiosis often observed among patients with IBS. Trial registration ClinicalTrials.gov: NCT02161120. Retrospectively registered 11 June 2014.

Abstract Background Type 1 neurofibromatosis (NF1) is a genetic tumor predisposing Rasopathy. NF1 patients have an increased risk for developing benign and malignant tumors, but the occurrence of intestinal tumors has not been investigated at the population level. Methods In this retrospective register‐based total population study, diagnoses of gastrointestinal tract tumors were retrieved from the Finnish Care Register for Health Care for 1,410 NF1 patients and 14,030 reference persons. We also reviewed the death certificates of 232 NF1 patients who died during years 1987–2013, and specifically searched for diagnosis of gastrointestinal stromal tumor (GIST). Results The register analysis revealed an increased overall hazard ratio (HR) of 2.6 (95% CI 1.9–3.6) for intestinal tumors in NF1 compared to general population. The highest HR of 15.6 (95% CI 6.9–35.1) was observed in the small intestine. The focused analysis of NF1 death certificates and GISTs demonstrated that the GIST was the primary cause of death in seven patients. Conclusion This study emphasizes the need for careful evaluation of NF1 patients with gastrointestinal complaints. The challenge in diagnosis is that the tumors preferably occur at the small intestine, which is difficult target for diagnostic procedures. We also show that the NF1 GISTs may lead to fatal outcome despite of benign histopathological findings at the time of the diagnosis.

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The ingestion of gluten-containing foods can cause wheat-related disorders in up to 15% of wheat consuming populations. Besides the role of gluten, α-amylase/trypsin inhibitors (ATI) have recently been identified as inducers of an innate immune response via toll-like receptor 4 in celiac disease and non-celiac wheat sensitivity. ATI are involved in plant self-defense against insects and possibly in grain development. Notably, they are largely resistant to gastrointestinal proteases and heat, and their inflammatory activity affects not only the intestine, but also peripheral organs. The aim of this study was to understand the changes of ATI throughout the sourdough and yeast-fermented bread-making processes. ATI tetramers were isolated, fluorescein-labelled, and added to a mini-dough bread-making system. When the pH decreased below 4.0 in sourdough fermentation, the ATI tetramers were degraded due to the activation of aspartic proteases, whilst in yeast fermentation, ATI tetramers remained intact. The amylase inhibitory activity after sourdough fermentation decreased significantly, while the concentration of free thiol groups increased. The glutathione reductase activity of Fructilactobacillus sanfranciscensis did not contribute to the reduction of ATI tetramers. Compared to the unfermented wheat, sourdough fermentation was able to decrease the release of pro-inflammatory cytokines monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor alpha (TNF-α) in quantitative ATI extracts added to the human monocytic cell line THP-1. The current data suggest that sourdough fermentation can degrade ATI structure and bioactivity, and point to strategies to improve product development for wheat sensitivity patients.

Background: There is a lack of knowledge on the association between daily physical activity and lung function in patients with asthma. Objective: This study aims to examine the association between daily physical activity and asthma control, lung function, and lung function decline in patients with adult-onset asthma. Design: This study is part of Seinäjoki Adult Asthma Study (SAAS), where 201 patients were followed for 12 years after asthma diagnosis. Daily physical activity was assessed at follow-up by a structured questionnaire and used to classify the population into subgroups of low (≤240 min) or high (>240 min) physical activity. Three spirometry evaluation points were used: 1. diagnosis, 2. the maximum lung function during the first 2.5 years after diagnosis (Max0-2.5), 3. follow-up at 12 years. Results: High physical activity group had slower annual FEV1 (p

A low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet allows most irritable bowel syndrome (IBS) patients to manage their gastrointestinal symptoms by avoiding FODMAP-containing foods, such as onions, pulses, and products made from wheat or rye. The downside of a low FODMAP diet is the reduced intake of dietary fiber. Applying sourdoughs—with specific FODMAP-targeting metabolic properties—to wholegrain bread making can help to remarkably reduce the content of FODMAPs in bread without affecting the content of the slowly fermented and well-tolerated dietary fiber. In this review, we outline the metabolism of FODMAPs in conventional sourdoughs and outline concepts related to fructan and mannitol metabolism that allow development of low FODMAP sourdough bread. We also summarize clinical studies where low FODMAP but high fiber, rye sourdough bread was tested for its effects on gut fermentation and gastrointestinal symptoms with very promising results. The sourdough bread-making process offers a means to develop natural and fiber-rich low FODMAP bakery products for IBS patients and thereby help them to increase their dietary fiber intake.