Objective We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS). Design A prospective pre-specified secondary endpoint analysis of 49 patients with confirmed PA, of whom 29 underwent unilateral adrenalectomy with long-term follow-up. Methods Concentrations of androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were measured during AVS in addition to aldosterone and cortisol. Subjects with lateralisation index (LI) of >= 4 were treated with unilateral adrenalectomy, and the immunohistochemical subtype was determined with CYP11B2 and CYP11B1 stains. The performance of adrenal androgens was evaluated by receiver operating characteristics (ROC) curve analyses in adrenalectomy and medical therapy groups. Results During AVS, the correlations between cortisol and androstenedione, DHEA and DHEAS for LI and selectivity index (SI) were highly significant. The right and left side SIs for androstenedione and DHEA were higher (p < .001) than for cortisol. In ROC analysis, the optimal LI cut-off values for androstenedione, DHEA and DHEAS were 4.2, 4.5 and 4.6, respectively. The performance of these LIs for adrenal androgens did not differ from that of cortisol. Conclusions Under cosyntropin-stimulated AVS, the measurement of androstenedione and DHEA did not improve the cannulation selectivity. The performance of cortisol and adrenal androgens are confirmatory but not superior to cortisol-based results in lateralisation diagnostics of PA.

Background: In 2009, a classification system for the open abdomen was introduced. The aim of such a classification is to aid the (1) description of the patient's clinical course; (2) standardization of clinical guidelines for guiding open abdomen management; and (3) facilitation of comparisons between studies and heterogeneous patient populations, thus serving as an aid in clinical research. Methods: As part of the revision of the definitions and clinical guidelines performed by the World Society of the Abdominal Compartment Syndrome, this 2009 classification system was amended following a review of experiences in teaching and research and published as part of updated consensus statements and clinical practice guidelines in 2013. Among 29 articles citing the 2009 classification system, nine were cohort studies. They were reviewed as part of the classification revision process. A total of 542 patients (mean: 60, range: 9-160) had been classified. Two problems with the previous classification system were identified: the definition of enteroatmospheric fistulae, and that an enteroatmospheric fistula was graded less severe than a frozen abdomen. Results: The following amended classification was proposed: Grade 1, without adherence between bowel and abdominal wall or fixity of the abdominal wall (lateralization), subdivided as follows: 1A, clean; 1B, contaminated; and 1C, with enteric leak. An enteric leak controlled by closure, exteriorization into a stoma, or a permanent enterocutaneous fistula is considered clean. Grade 2, developing fixation, subdivided as follows: 2A, clean; 2B, contaminated; and 2C, with enteric leak. Grade 3, frozen abdomen, subdivided as follows: 3A clean and 3B contaminated. Grade 4, an established enteroatmospheric fistula, is defined as a permanent enteric leak into the open abdomen, associated with granulation tissue. Conclusions: The authors believe that, with these changes, the requirements on a functional and dynamic classification system, useful in both research and training, will be fulfilled. We encourage future investigators to apply the system and report on its merits and constraints.

Purpose To determine the risk of patients with an early diagnosis of heritable retinoblastoma being diagnosed with TRb (or pineoblastoma) asynchronously in a later stage and its effect on screening. Methods We updated the search (PubMed and Embase) for published literature as performed by our research group in 2014 and 2019. Trilateral retinoblastoma (TRb) patients were eligible for inclusion if identifiable as unique and the age at which TRb was diagnosed was available. The search yielded 97 new studies. Three new studies and eight new patients were included. Combined with 189 patients from the previous meta-analysis, the database included 197 patients. The main outcome was the percentage of asynchronous TRb in patients diagnosed before and after preset age thresholds of 6 and 12 months of age at retinoblastoma diagnosis. Results Seventy-nine per cent of patients with pineoblastoma are diagnosed with retinoblastoma before the age of 12 months. However, baseline MRI screening at time of retinoblastoma diagnosis fails to detect the later diagnosed pineal TRb in 89% of patients. We modelled that an additional MRI performed at the age of 29 months picks up 53% of pineoblastomas in an asymptomatic phase. The detection rate increased to 72%, 87% and 92%, respectively, with 2, 3 and 4 additional MRIs. Conclusions An MRI of the brain in heritable retinoblastoma before the age of 12 months misses most pineoblastomas, while retinoblastomas are diagnosed most often before the age of 12 months. Optimally timed additional MRI scans of the brain can increase the asymptomatic detection rate of pineoblastoma.

The incidence of cutaneous squamous cell carcinoma is increasing worldwide. In most epidemiological studies, only the first case of cutaneous squamous cell carcinoma is registered, underestimating the burden of the disease. To determine the frequency and detailed characteristics of cutaneous squamous cell carcinoma in a Finnish patient cohort, we performed a retrospective 10-year study taking into account multiple tumours in one patient. On the pathology database search and medical record review we identified 774 patients with a total of 1,131 cutaneous squamous cell carcinomas. The crude incidence increased from 18.6/100,000 persons in 2006 to 28.1 in 2015. The location of tumours differed between men and women: the greatest difference concerned cutaneous squamous cell carcinoma of the ear, with 93% of cases occurring in men. One fourth (24%) of patients had more than one tumour. A small shift from poorly to well-differentiated tumours was seen. In conclusion, the incidence of cutaneous squamous cell carcinoma increased, with many patients presenting with multiple tumours.

Aim: The effect of conservative versus liberal oxygen therapy on mortality rates in post cardiac arrest patients is uncertain. Methods: We undertook an individual patient data meta-analysis of patients randomised in clinical trials to conservative or liberal oxygen therapy after a cardiac arrest. The primary end point was mortality at last follow-up. Results: Individual level patient data were obtained from seven randomised clinical trials with a total of 429 trial participants included. Four trials enrolled patients in the pre-hospital period. Of these, two provided protocol-directed oxygen therapy for 60 min, one provided it until the patient was handed over to the emergency department staff, and one provided it for a total of 72 h or until the patient was extubated. Three trials enrolled patients after intensive care unit (ICU) admission and generally continued protocolised oxygen therapy for a longer period, often until ICU discharge. A total of 90 of 221 patients (40.7%) assigned to conservative oxygen therapy and 103 of 206 patients (50%) assigned to liberal oxygen therapy had died by this last point of followup; absolute difference; odds ratio (OR) adjusted for study only; 0.67; 95% CI 0.45 to 0.99; P = 0.045; adjusted OR, 0.58; 95% CI 0.35 to 0.96; P = 0.04. Conclusion: Conservative oxygen therapy was associated with a statistically significant reduction in mortality at last follow-up compared to liberal oxygen therapy but the certainty of available evidence was low or very low due to bias, imprecision, and indirectness. PROSPERO registration number: CRD42019138931.

It is uncertain how the traditional forest sector can respond to the changing political environment, evolving markets, and global environmental problems. This study focuses on the development of forest-based bioeconomy (BE) in Finland from the perspective of three forest-based value networks (wooden multistory construction, fiber-based packaging, and biorefining) and thus breaks the tendency of siloed discussions. The study of expert opinions applies a collaborative interdisciplinary research method that combines group discussions and follow-up survey data. The results indicate that transformational regulation, proper incentives, and ways of increasing interaction at the business-consumer interface are required to support the creation of new practices and the destruction of old practices in the industry renewal. (C) 2021 The Authors. Published by Elsevier Ltd.

Background: We describe the phenotypic spectrum and timing of diagnosis and management in a large series of patients with disorders of sexual development (DSD) treated in a single pediatric tertiary center. Methods: DSD patients who had visited our tertiary center during the survey period (between 2004 and 2014) were identified based on an ICD-10 inquiry, and their phenotypic and molecular genetic findings were recorded from patient charts. Results: Among the 550 DSD patients, 53.3% had 46,XY DSD; 37.1% had sex chromosome DSD and 9.6% had 46,XX DSD. The most common diagnoses were Turner syndrome (19.8%, diagnosed at the mean age of 4.7 +/- 5.5 years), Klinefelter syndrome (14.5%, 6.8 +/- 6.2 years) and bilateral cryptorchidism (23.1%). Very few patients with 46,XY DSD (7%) or 46,XX DSD (21%) had molecular genetic diagnosis. The yearly rate of DSD diagnoses remained stable over the survey period. After the release of the Nordic consensus on the management of undescended testes, the age at surgery for bilateral cryptorchidism declined significantly (P <0.001). Conclusions: Our results show that (i) Turner syndrome and Klinefelter syndrome, the most frequent single DSD diagnoses, are still diagnosed relatively late; (ii) a temporal shift was observed in the management of bilateral cryptorchidism, which may favorably influence patients' adulthood semen quality and (iii) next-generation sequencing methods are not fully employed in the diagnostics of DSD patients.

Background: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Colorectal cancer: essential requirements for quality care Colorectal cancer (CRC) is the second most common cause of cancer death in Europe and has wide variation in outcomes among countries. Increasing numbers of older people are contracting the disease, and treatments for advanced stages are becoming more complex. A growing number of survivors also require specialist support. High-quality care can only be a carried out in specialised CRC units or centres which have both a core multidisciplinary team and an extended team of allied professionals, and which are subject to quality and audit procedures. Such units or centres are far from universal in all European countries. It is essential that, to meet European aspirations for comprehensive cancer control, healthcare organisations implement the essential requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship. Conclusion: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality CRC service. The ECCO expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with CRC. (C) 2016 The Authors. Published by Elsevier Ireland Ltd.

Dupilumab, a fully human monoclonal antibody against interleukin-4 receptor alpha, is approved as add-on maintenance treatment for inadequately controlled type 2 severe asthma. This systematic review evaluated the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled severe asthma. PubMed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important asthma-related outcomes were evaluated. The risk of bias and the certainty of the evidence were assessed using GRADE. Three RCTs including 2735 subjects >12 years old and 24-52 weeks of follow-up were included. Dupilumab reduced with high certainty severe asthma exacerbations (Incidence rate ratio 0.51; 95% CI 0.45-0.59) and the percentage use of oral corticosteroid use (mean difference (MD) -28.2 mg/d; 95% CI -40.7 to -15.7). Asthma control (ACQ-5), quality of life (AQLQ) and rescue medication use [puffs/d] improved, without reaching the minimal important clinical difference: ACQ-5 MD -0.28 (95% CI -0.39 to -0.17); AQLQ MD +0.28 (95% CI 0.20-0.37); and rescue medication MD -0.35 (95% CI -0.73 to +0.02). FEV1 increased (MD +0.15; 95% CI +0.11 to +0.18) (moderate certainty). There was an increased rate of dupilumab-related adverse events (AEs) (moderate certainty) and of drug-related serious AEs (low certainty). The incremental cost-effectiveness ratio of dupilumab versus standard therapy was 464 000$/QALY (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population.

Background There is a lack of agreement about applicable instrument to screen frailty in clinical settings. Aims To analyze the association between frailty and mortality in Finnish community-dwelling older people. Methods This was a prospective study with 10- and 18-year follow-ups. Frailty was assessed using FRAIL scale (FS) (n = 1152), Rockwood's frailty index (FI) (n = 1126), and PRISMA-7 (n = 1124). To analyze the association between frailty and mortality, Cox regression model was used. Results Prevalence of frailty varied from 2 to 24% based on the index used. In unadjusted models, frailty was associated with higher mortality according to FS (hazard ratio 7.96 [95% confidence interval 5.10-12.41] in 10-year follow-up, and 6.32 [4.17-9.57] in 18-year follow-up) and FI (5.97 [4.13-8.64], and 3.95 [3.16-4.94], respectively) in both follow-ups. Also being pre-frail was associated with higher mortality according to both indexes in both follow-ups (FS 2.19 [1.78-2.69], and 1.69 [1.46-1.96]; FI 1.81[1.25-2.62], and 1.31 [1.07-1.61], respectively). Associations persisted even after adjustments. Also according to PRISMA-7, a binary index (robust or frail), frailty was associated with higher mortality in 10- (4.41 [3.55-5.34]) and 18-year follow-ups (3.78 [3.19-4.49]). Discussion Frailty was associated with higher mortality risk according to all three frailty screening instrument used. Simple and fast frailty indexes, FS and PRISMA-7, seemed to be comparable with a multidimensional time-consuming FI in predicting mortality among community-dwelling Finnish older people. Conclusions FS and PRISMA-7 are applicable frailty screening instruments in clinical setting among community-dwelling Finnish older people.