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Sanna Toppila-Salmi,1,2 Leif Bjermer,3 Lars-Olaf Cardell,4,5 Anders Cervin,6,7 Tuuli Heinikari,2 Lauri Lehtimäki,8,9 Marie Lundberg,10 Jens C Richter,11 Saara Sillanpää9,12 1Department of Otorhinolaryngology, Kuopio University Hospital and School of Medicine, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; 2Skin and Allergy Hospital, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 3Department of Clinical Sciences, Respiratory Medicine and Allergology, Lund University, Lund, Sweden; 4Division of ENT Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; 5Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden; 6Centre for Clinical Research, University of Queensland, Brisbane, Australia; 7Faculty of Medicine, Lund University, Lund, Sweden; 8Allergy Centre, Tampere University Hospital, Tampere, Finland; 9Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; 10Department of Otorhinolaryngology – Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland; 11Department of Asthma and Allergology, Clinic of Lung Medicine, Skåne University Hospital and Lund University, Lund, Sweden; 12Department of Otorhinolaryngology and Head and Neck Surgery, Tampere University Hospital, Tampere, FinlandCorrespondence: Sanna Toppila-Salmi, Haartmaninkatu 3, Haartman Institute, University of Helsinki, Helsinki, 00014, Finland, Email sanna.salmi@helsinki.fiAbstract: Severe chronic rhinosinusitis with nasal polyposis (CRSwNP) is a disabling airway disease that significantly impacts patients’ lives through the severity of symptoms, the need for long-term medical treatment and the high risk of recurrence post-surgery. Biological agents targeting type 2 immune responses underlying the pathogenesis of CRSwNP have shown effectiveness in reducing polyp size and eosinophilic infiltrate, and in decreasing the need for additional sinus surgeries. However, despite recent progress in understanding and treating the disease, type 2 inflammation-driven severe CRSwNP continues to pose challenges to clinical management due to several factors such as persistent inflammation, polyp recurrence, heterogeneity of disease, and comorbidities. This article presents the findings of a scientific discussion involving a panel of ear, nose and throat (ENT) specialists and pulmonologists across Sweden and Finland. The discussion aimed to explore current management practices for type 2 inflammation-driven severe CRSwNP in the Nordic region. The main topics examined encompassed screening and referral, measurements of disease control, treatment goals, and future perspectives. The experts emphasized the importance of a collaborative approach in the management of this challenging patient population. The discussion also revealed a need to broaden treatment options for patients with type 2 inflammation-driven CRSwNP and comorbid conditions with shared type 2 pathophysiology. In light of the supporting evidence, a shift in the disease model from the presence of polyps to that of type 2 inflammation may be warranted. Overall, this discussion provides valuable insights for the scientific community and can potentially guide the future management of CRSwNP.Keywords: chronic rhinosinusitis, type 2 immunity, surgery, biological therapy, Nordic countries, collaboration

Aims: The aim of the study was to describe child health in relation to housing renovations in more than 800 rental units, consisting of repairs of dilapidated kitchens and bathrooms, in the disadvantaged neighbourhood of Herrgården in Rosengård, Malmö, Sweden., Methods: Data on housing conditions and self-reported health were collected during home visits to families living in Herrgården (building renovations area) and a comparison area (neighbouring Törnrosen, with generally better housing conditions). At baseline, 130 families with 359 children participated, while 51 families with 127 children participated at follow-up. All data were collected between 2010 and 2012. Additionally, regional register data on health-care usage/in- and outpatient contacts within the public health-care system between 2008 and 2013 were also collected for all 8715 children registered as living in the two areas., Results: Self-reported health seemed to somewhat improve in both areas, with 74% versus 86% and 78% versus 88% reporting good or very good health in Herrgården and in the comparison area at baseline and follow-up, respectively. In Herrgården, crowdedness increased, while it decreased in the comparison area. The number of health-care contacts remained stable over time in Herrgården, while it decreased in the comparison area., Conclusions: Partial housing renovations did not seem to result in clear health improvements as measured with the indicators used in the present study. This could possibly be due to persisting health effects due to increased crowdedness or persisting poor housing conditions, as only kitchens and bathrooms were renovated.

The development of crop varieties with stable performance in future environmental conditions represents a critical challenge in the context of climate change. Environmental data collected at the field level, such as soil and climatic information, can be relevant to improve predictive ability in genomic prediction models by describing more precisely genotype-by-environment interactions, which represent a key component of the phenotypic response for complex crop agronomic traits. Modern predictive modeling approaches can efficiently handle various data types and are able to capture complex nonlinear relationships in large datasets. In particular, machine learning techniques have gained substantial interest in recent years. Here we examined the predictive ability of machine learning-based models for two phenotypic traits in maize using data collected by the Maize Genomes to Fields (G2F) Initiative. The data we analyzed consisted of multi-environment trials (METs) dispersed across the United States and Canada from 2014 to 2017. An assortment of soil- and weather-related variables was derived and used in prediction models alongside genotypic data. Linear random effects models were compared to a linear regularized regression method ( elastic net ) and to two nonlinear gradient boosting methods based on decision tree algorithms ( XGBoost, LightGBM ). These models were evaluated under four prediction problems: (1) tested and new genotypes in a new year; (2) only unobserved genotypes in a new year; (3) tested and new genotypes in a new site; (4) only unobserved genotypes in a new site. Accuracy in forecasting grain yield performance of new genotypes in a new year was improved by up to 20% over the baseline model by including environmental predictors with gradient boosting methods. For plant height, an enhancement of predictive ability could neither be observed by using machine learning-based methods nor by using detailed environmental information. An investigation of key environmental factors using gradient boosting frameworks also revealed that temperature at flowering stage, frequency and amount of water received during the vegetative and grain filling stage, and soil organic matter content appeared as important predictors for grain yield in our panel of environments., Competing Interests: The 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 © 2021 Westhues, Mahone, da Silva, Thorwarth, Schmidt, Richter, Simianer and Beissinger.)

Background: Atopic disorders are a global concern. Studies in migrant populations can illuminate the interplay of genetic and environmental factors. Exposures related to bad housing (indoor dampness, mould growth, crowding etc.) are likely to play a role in how socioeconomic inequalities can turn into health disparities for disadvantaged populations. The sizable immigrant population living in very poor-quality housing in Malmö, Sweden, became the focus of a cross-sectional study., Objective: To describe atopic disorders and sensitizations in a population living in substandard housing in Malmö, Sweden, with an emphasis on their relation to harmful exposures from the built environment., Methods: Families were recruited via identification of any children with symptomatic airway afflictions from health care records, and also asymptomatic children from school lists. Interviewer-led health questionnaire data and data from self-reports about living conditions were obtained together with data from home inspections carried out by health communicators. Families underwent skin prick tests (SPT) against common aeroallergens., Results: As could be expected from background demographic information, it turned out that we effectively studied an immigrant population inhabiting very precarious housing outside the center of Malmö. A total of 359 children from 130 families (total 650 participants) were included. Overall the prevalence of potentially harmful environmental exposures was high (signs of moisture or mould in more than 50% of apartments, indoor smoking in 37% of households). Atopic disorders were common among both adults and children. SPTs showed a spectrum of sensitizations consistent with unselected populations in Sweden. Paternal sensitization in the SPT was associated with higher risk of sensitization for offspring than maternal sensitization. Few statistically significant associations of atopic sensitization with studied environmental exposures were detected (for example objective signs of dampness /mould in bathrooms). There were marked discrepancies between asthma diagnoses obtained from the health records and parental reports of such diagnoses and treatment for their children., Conclusions: The atopic burden in this selected immigrant population was high, and results point to unmet medical needs. Health care systems caring for such populations need to be aware of their specific health needs; comprehensive asthma and allergy care should include consideration of harmful environmental exposures, adhering to the precautionary principle., Competing Interests: Ethical approval for the study was granted by the Regional Ethical Review Board through Lund University (Registration number 2010/212).At the start of the home visit, informed written consent (in the native language of the family) for participation in the study was obtained from the parents. Children assented verbally to skin prick testing.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Objectives: To describe the home environment in terms of housing conditions and their association with child health in a disadvantaged immigrant population., Design: A cross-sectional observational study., Setting: Enrolment took place during 2010-2011 in Rosengård, Malmö, Sweden., Participants: Children aged 0-13 years in 2 study neighbourhoods were recruited from local health records and from schools. 359 children participated, with a participation rate of 40%. Data on health, lifestyle and apartment characteristics from questionnaire-led interviews with the mothers of the children were obtained together with data from home inspections carried out by trained health communicators., Outcome Measures: Logistic regression analysis was used to estimate ORs for various health outcomes, adjusted for demographic information and lifestyle factors., Results: The housing conditions were very poor, especially in one of the study neighbourhoods where 67% of the apartments had been sanitised of cockroaches, 27% were infested with cockroaches and 40% had a visible mould. The association between housing conditions and health was mostly inconclusive, but there were statistically significant associations between current asthma and dampness (OR=4.1, 95% CI 1.7 to 9.9), between asthma medication and dampness (OR=2.8, 95% CI 1.2 to 6.4), and between mould and headache (OR=4.2, 95% CI 1.2 to 14.8). The presence of cockroaches was associated with emergency care visits, with colds, with headache and with difficulty falling asleep, and worse general health was associated with mould and presence of cockroaches., Conclusions: The associations between dampness and asthma, and the association between mould and headache, are in line with current knowledge. The presence of cockroaches seemed to be associated with various outcomes, including those related to mental well-being, which is less described in the literature. The results of the present study are hypothesis generating and provide strong incentives for future studies in this study population., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Using 5-aminolevulinic acid (ALA) as an intraoperative fluorescence contrast has been proven to improve the resection of glioblastoma and contribute to prolonged patient survival. ALA accumulates as protoporphyrin IX (PpIX) in the tumor cells and is administered in an advised dose of 20 mg/kg body weight (b.w.) for brain tumor resection using fluorescence surgical microscopes. PpIX fluorescence availability and intensities of a four folds lower ALA dose (5 mg/kgb.w.) has been investigated in glioblastomas and skin using a spectroscopy system adapted for surgical guidance., Methods: A total of 30 adult patients diagnosed with high grade gliomas were included in the analysis. ALA was orally administered in doses of 5 mg/kg b.w. (n = 15) dissolved in orange juice or 20 mg/kgb.w. (n = 15) dissolved in water. A fluorescence spectroscopy system with a handheld fiber-optical probe was used for performing the quantitative fluorescence measurements., Results: The binominal comparison of the diagnostic performance parameters showed no significant statistical difference (p > 0.05). The median fluorescence values in tumor were 2-3 times higher for the high ALA dose group. No PpIX was detected in the skin of the patients in the low dose group (0/4) while PpIX was detected in the skin of the majority of the patients in the high ALA dose group (13/14)., Conclusions: Application of 5mg/kg ALA was evaluated as equally reliable as the higher dose regarding the diagnostic performance when guidance was performed using a spectroscopic system. Moreover, no PpIX was detected in the skin of the patients., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Aim: To measure the prevalence of exposure to potentially modifiable risk factors in the homes of children hospitalised in Wellington., Methods: Parents/caregivers of all children admitted to Wellington Public Hospital during a two-week period in July 2012 completed a standardised questionnaire in a face-to-face interview. The questionnaire collected sociodemographic, health and housing condition data., Results: We interviewed parents/caregivers of 106 children, of whom 72% were aged 0-4 years. Respiratory conditions were the most common cause of admission. One third of parents noticed dampness and mould in their house, 50% stated that their house was colder than they preferred during the past month, 20% lived in uninsulated houses, 20% lived in overcrowded houses, and 38% were exposed to second hand smoke (SHS). Compared to New Zealand European (NZE) children, the odds ratios (OR) for Pacific children living in cold and overcrowded houses and being exposed to SHS were 14.0 (95%CI 3.0-66.0), 10.8 (95%CI 2.6-44.1) and 16.0 (95%CI 4.8-55.5) respectively. OR for Maori children living in cold and overcrowded houses and being exposed to SHS were 3.0 (95%CI 1.0-9.0), 6.8 (95%CI 1.6-30.1) and 8.0 (95%CI 2.5-28.6) respectively, compared to NZE children. The OR for children from deprived neighbourhoods (NZDep2006 areas 7-10) living in cold and overcrowded houses and being exposed to SHS were 4.1 (95%CI 1.8-9.6), 5.7 (95%CI 1.9-17.0) and 4.1 (95%CI 1.6-9.6) respectively., Conclusions: Among children admitted to Wellington Hospital there is a high prevalence of exposure to cold, damp and overcrowded houses and many children are exposed to SHS. Maori and Pacific children and children living in socioeconomically deprived areas are more likely than others to be exposed to these potential risk factors for childhood hospitalisation. This audit of child admissions could be repeated to provide surveillance of modifiable risk factors. A shortened version of the questionnaire could be used to screen children to identify those with harmful exposures in their home environment, provided suitable intervention programmes can be established.

Background and Objective: Glioblastoma multiforme is a highly malignant primary brain tumor. It has no border but at best a marginal zone, however, invisible to the surgeon. An optical touch pointer (OTP) enabling differentiation of healthy and tumor tissue by means of fiber-optic fluorescence spectroscopy has been developed. In combination with an ultrasonic navigation system, the OTP may be used for demarcation of resectable tumor tissue. The aim of the study was to evaluate the clinical performance of OTP during surgery of malignant brain tumors., Study Design/materials and Methods: Nine patients were operated on with the standard surgical procedure, including white light microscopy and navigation. A total of 5 mg/kg bodyweight of 5-amino-levulin acid was orally administrated before surgery. The OTP was calibrated into the ultrasound-based navigation system and measurements were performed in tumor core and along the tumor border. The ratio between the protoporphyrin IX fluorescence at 635 nm and the autofluorescence was used for quantifications of data. Biopsies (n = 20), ultrasound images (n = 30), and visual inspection (n = 180) were compared to the fluorescence ratio., Results/conclusion: Healthy and tumor tissue could be identified and differentiated with the OTP (P < 0.001). The fluorescence ratio in average was 0 outside the tumor and low in the gliotic edema zone around the tumor. It increased in the marginal zone and was highest in the solid tumor tissue. In the necrotic tissue, in the center of the tumor, the ratio in average was 0. The OTP can be used in combination with ultrasound-based navigation and may help to determine whether to resect otherwise not identifiable tissue., (Copyright © 2011 Wiley Periodicals, Inc.)

A 71-year-old man sustains multiple fractures in an accident; after a lucid interval he deteriorates neurologically and becomes comatose. Intracranial hemorrhage, status epilepticus, adverse drug reactions, toxic-metabolic, ischemic or infectious causes are subsequently ruled out. Development of petechiae and thrombopenia raises the possibility of fat embolism syndrome, which is confirmed in a MRI of the head 72 hours after the accident. We discuss current aetiologic concepts as well as diagnosis and clinical course of the cerebral fat embolism syndrome.

History and Clinical Findings: A 69-year-old man was admitted with cough, fever and dyspnea. For years, an adrenal insufficiency has been substituted with low-dose hydrocortisone. The hypotensive and tachycardic patient exhibited remarkable stony hard ears., Investigations: Elevated inflammatory markers and the clinical picture point to a pulmonary focus of infection. Radiographs of the ears show trabecular structures as a sign of true ossification., Diagnosis, Treatment and Course: Addisonian crisis due to pulmonary infection was treated successfully with steroids, antibiotics and intravenous fluids. The auricular ossification was interpreted as a secondary phenomenon of undersubstituted adrenal insufficiency., Conclusion: Adrenal insufficiency should be considered when auricular ossification is encountered. The pathogenesis of this phenomenon is complex and not well understood., (Georg Thieme Verlag KG Stuttgart * New York.)

A patient with a red, painful eye and gradual visual impairment is examined ophthalmologically. Culture of the vitreal aspirate yields Candida tropicalis. Subsequent medical evaluation reveals that during an acute hospitalization eight weeks prior positive blood cultures for Candida had been reported but not acted on, despite a high risk constellation of operative therapy, intensive care unit treatment, central catheters, parenteral nutrition and broad spectrum antibiotics. Diagnosis and treatment of candidemia with a focus on candida endophthalmitis is discussed.

Background: Psychiatric emergency situations (PES) are of high importance to the German prehospital physician-based emergency medical system. So far, however, no prospective studies regarding the incidence of PES have been performed, neither have effects of training programs on diagnostic and therapeutic accuracy been studied., Method: The protocols of two emergency medical services (EMS) were collected and analyzed prospectively. Emergency physicians (EPs) in Kaiserslautern (KL) attended a standardized educational program and underwent daily supervision. EPs in Homburg (HOM) had not been informed about the study. In KL, sociodemographic variables were collected. An investigator who was not involved in the individual EMS mission assessed the correct classification of PES., Results: Among all calls for an EP, 11.8% were classified as PES. There was no difference between the two centers. Correct classification of PES in KL was significantly higher than that in HOM (94.3% vs. 80.6%). Documentation of suicidal behavior was deficient in both centers. EPs in KL gave verbal crisis intervention significantly more often, administered less medication overall, and dispensed more specific drugs in psychotic disorders and significantly less drugs in substance abuse disorders. Patients were more often treated at the scene and were less often transported to a hospital. Some sociodemographic variables were associated with psychiatric morbidity of treatment., Conclusion: Accounting for 12% of all missions, psychiatric emergencies are a frequent reason for calls for EPs, equaling trauma-related and neurological emergencies. The most frequent reasons for calls were alcohol intoxication, states of agitation and suicidal behavior. The diagnostic and therapeutic accuracy of EPs may be improved with a concise standardized teaching program.

The purpose of the study was to investigate the prevalence of posttraumatic stress disorder (PTSD) after prolonged intensive care unit (ICU) treatment and to study the differences between trauma patients and patients who were admitted with other diagnoses. Survivors of surgical intensive care of at least 30 days' duration underwent follow-up examination at about 35 months after discharge from the ICU. Thirty-seven patients were investigated. Seven patients met full DSM-IV criteria for diagnosis of PTSD. All of them had sustained severe multiple injuries. Patients with trauma were at significantly higher risk for developing PTSD than were non-trauma patients. After prolonged ICU treatment, PTSD seems more likely to occur when the reason for admission to the ICU was severe physical injury. The prevalence of PTSD does not seem to be related to injury severity or duration of ICU treatment.

We present the case of a young woman that was diagnosed with Churg-Strauss syndrome. The classical as well as the atypical symptoms, signs and findings are discussed in the context of clinically relevant differential diagnoses. The diagnostic criteria and the relevant aspects of pathogenesis, clinical course and treatment are reviewed. In addition, the similarities and differences with respect to the other idiopathic interstitial eosinophilic pneumopathies are described.

Introduction: Long-term treatment in surgical intensive care units (SICU) subjects the patient to a high degree of somatic, psychological, and social stress. The aim of this study was to determine their outcome in terms of quality of life and health status., Methods: All patients from a 4-year period in a SICU with a length of stay (LOS) of 30 days or more were included. All survivors were interviewed and examined after 35 +/- 14 months; they also completed several questionnaires (Munich Inventory for Quality of Life and Health Status, POMS, and Spitzer Quality of Life Index)., Results: One hundred one patients fulfilled the inclusion criteria, and 46 survived until follow-up. Forty-one (89%) could be traced and examined. Male:female ratio was 31:10, age 42 +/- 17 years, and LOS 51 +/- 19 days, Diagnoses on admittance were multiple trauma (n = 32) and other (n = 9). When classifying patients according to physical impairment, one third each showed no, mediocre, or severe limitations. Subjective appraisal of quality of life and well-being was sufficient for about half the patients in every test. Trauma victims experienced more severe impairment of quality of life. There were no differences between sex, age, or time until follow-up., Conclusion: After prolonged SICU treatment, about half of the patients report limitations in their quality of life as a result of their illness and the subsequent treatment. Some patients, in particular after trauma, exhibit striking psychosocial problems despite satisfactory somatic treatment results. These problems can be positively addressed in rehabilitative efforts.

The time course of pancreatic effects of somatostatin was studied over a period of 2 h in unanesthetized unrestrained rats after administration of the peptide by intravenous infusion and by single and multiple subcutaneous injections. During infusion of 10 and 30 micrograms/kg per min, somatostatin continuously suppressed plasma insulin and plasma glucagon. Plasma glucose was significantly increased at the lower dose, but not affected at the higher dose. Single subcutaneous injections of 0.3 and 3 mg/kg decreased plasma insulin and glucagon dose-dependently for 20-60 min without affecting plasma glucose. Multiple subcutaneous injections of somatostatin (one to four doses of 3 mg/kg, administered at intervals of 30 min) caused an initial decrease of plasma insulin (at 30 min), a rebound-increase at 60 and 90 min, and a final return to control values by 120 min. Plasma glucagon remained continuously suppressed. Plasma glucose increased significantly at 60 and 90 min and tended to return towards control values thereafter. In conclusion, pancreatic B cells - but not A cells - of the rat develop tachyphylaxis to somatostatin within 2 h after multiple subcutaneous injections of the peptide. By this mode of administration, 'selective' suppression of plasma glucagon can be achieved with somatostatin in the rat.