Search

Eetu Heervä,1 Vesa Väliaho,1 Heidi Nurmi,1 Elina Lietzen,2 Annika Ålgars,1 Saila Kauhanen2 1Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland; 2Department of Digestive Surgery, Turku University Hospital and University of Turku, Turku, FinlandCorrespondence: Eetu Heervä, Department of Oncology, Turku University Hospital, Hämeentie 11, Turku, 20521, Finland, Tel +35823130000, Fax +35823131316, Email eetu.heerva@utu.fiBackground: Pancreatic ductal adenocarcinoma (PDAC) remains a lethal and rarely resectable malignancy. Here we explore the outcomes of surgery, as compared to definitive radiotherapy (dRT) or systemic therapy only in PDAC.Methods: Pancreatic surgery and radiotherapy in Southwest Finland have been centralized to Turku University Hospital. Previously validated population-based electronic health records database was searched for all unselected PDAC patients from the years 2009– 2019. Main outcome was median overall survival (mOS). Demographics, pathology, surgery, and oncological treatment data were collected.Results: We identified 1006 patients with PDAC, 49% male, median age 71 years and 77% presenting with metastatic disease. In total, 405 patients were treated; 92 resected, 26 dRT without resection and 287 systemic therapy only. mOS was 34.6 months for resected, 26.7 months for dRT, and 7.5 months for systemic therapy patients. Among the 88 patients with locally advanced inoperable PDAC, dRT was independently associated with longer mOS (26.7 months) as compared to systemic therapy only (mOS 10.6 months). Among the 287 patients treated with systemic therapy only, combination chemotherapy was independently associated with longer mOS (11.6 months) as compared to gemcitabine-monotherapy (6.8 months). In patients progressing to second-line systemic treatment after gemcitabine failure, mOS was the same (5.0 months) with single or combination regimens.Conclusion: Surgery remains the only curative approach for PDAC. In locally advanced PDAC, dRT was associated with longer survival as compared to systemic therapy only. Concerning first-line systemic therapy, our results support the use of combination chemotherapy over single-agent therapy.Keywords: pancreatic cancer, pancreas, pancreatectomy, nab-paclitaxel, chemoradiotherapy

Background: In patients with a degenerative tear of the medial meniscus, recent meta-analyses and systematic reviews have shown no treatment benefit of arthroscopic partial meniscectomy (APM) over conservative treatment or placebo surgery. Yet, advocates of APM still argue that APM is cost effective. Giving advocates of APM their due, we note that there is evidence from the treatment of other musculoskeletal complaints to suggest that a treatment may prove cost effective even in the absence of improvements in efficacy outcomes, as it may lead to other benefits, such as diminished productivity loss and reduced costs, and so the question of cost effectiveness needs to be answered for APM., Questions/purposes: (1) Does APM result in lower postoperative costs compared with placebo surgery? (2) Is APM cost-effective compared with placebo surgery?, Methods: One hundred forty-six adults aged 35 to 65 years with knee symptoms consistent with a degenerative medial meniscus tear and no knee osteoarthritis according to the American College of Rheumatology clinical criteria were randomized to APM (n = 70) or placebo surgery (n = 76). In the APM and placebo surgery groups, mean age was 52 ± 7 years and 52 ± 7 years, and 60% (42 of 70) and 62% (47 of 76) of participants were men, respectively. There were no between-group differences in baseline characteristics. In both groups, a standard diagnostic arthroscopy was first performed. Thereafter, in the APM group, the torn meniscus was trimmed to solid meniscus tissue, whereas in the placebo surgery group, APM was carefully mimicked but no resection of meniscal tissue was performed; as such, surgical costs were the same in both arms and were not included in the analyses. All patients received identical postoperative care including a graduated home-based exercise program. At the 2-year follow-up, two patients were lost to follow-up, both in the placebo surgery group. Cost effectiveness over the 2-year trial period was computed as incremental net monetary benefit (INMB) for improvements in quality-adjusted life years (QALY), using both the societal (primary) and healthcare system (secondary) perspectives. To be able to consider APM cost effective, the CEA analysis should yield a positive INMB value. Nonparametric bootstrapping was used to assess uncertainty. Several one-way sensitivity analyses were also performed., Results: APM did not deliver lower postoperative costs, nor did it convincingly improve quality of life scores when compared with placebo surgery. From a societal perspective, APM was associated with € 971 (95% CI -2013 to 4017) higher costs and 0.015 (95% CI -0.011 to 0.041) improved QALYs over 2-year follow-up compared with placebo surgery. Both differences were statistically inconclusive (a wide 95% CI that crossed the line of no difference). Using the conventional willingness to pay (WTP) threshold of € 35,000 per QALY, APM resulted in a negative INMB of € -460 (95% CI -3757 to 2698). In our analysis, APM would result in a positive INMB only when the WTP threshold rises to about € 65,000 per QALY. The wide 95% CIs suggests uncertain cost effectiveness irrespective of chosen WTP threshold., Conclusion: The results of this study lend further support to clinical practice guidelines recommending against the use of APM in patients with a degenerative meniscus tear. Given the robustness of existing evidence demonstrating no benefit or cost effectiveness of APM over nonsurgical treatment or placebo surgery, future research is unlikely to alter this conclusion.Level of Evidence Level III, economic analysis., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of Bone and Joint Surgeons.)

Background: Interstitial lung diseases (ILD) include a wide range of diseases impacting lung parenchyma and leading to fibrosis and architectural distortion. Chronic cough and dyspnea are common symptoms which affect the quality of life (QoL) in ILD patients. The mechanisms of cough in ILD patients are still unknown. The aim of this study was to prospectively investigate histological, radiological, and physiological determinants of cough-related QoL in ILD patients who underwent transbronchial lung cryobiopsy (TBLC)., Methods: All patients (n = 111) filled in The Leicester Cough Questionnaire (LCQ) and The St George's Respiratory Questionnaire (SGRQ). They underwent lung function tests, forced vital capacity (FVC), forced vital expiratory volume in 1 s (FEV1), diffusion capacity to carbon monoxide (DLCO), high-resolution computed tomography (HRCT), and blood samples before diagnostic TBLC. Two experienced radiologists assessed the extents of following HRCT patterns: ground-glass opacities (GGO), honeycombing, reticulation, traction bronchiectasis, and emphysema. Histology of TBLC were re-analyzed by two experienced pulmonary pathologists and the presence of fibroblast foci, fibrosis, giant cells, granulomas, and honeycombing were recorded., Results: In the median multivariate regression analysis, BMI (-0.19; 95% CI -0.37- -0.014; p 0.035), GGO (-0.38; 95% CI -0.61- -0.15; p 0.001), granulomas (-3.21; 95% CI -6.12- -0.30; p 0.031), and current smoking (2.49; 95% CI 0.12-4.86; p 0.040) showed independent associations with LCQ total score. BMI (1.3; 95% CI 0.20-2.42; p 0.021) and DLCO (-0.51; 95% CI -0.85 - -0.16; p 0.004) showed independent association with SGRQ total score., Conclusion: Determinants of cough-related QoL in ILD patients are multifactorial including physiological, radiological and histological parameters., (© 2024. The Author(s).)

Background: Medication review practices have evolved internationally in a direction in which not only physicians but also other healthcare professionals conduct medication reviews according to agreed practices. Collaborative practices have increasingly highlighted the need for electronic joint platforms where information on medication regimens and their implementation can be documented, kept updated, and shared., Objective: The aim of this study was to harmonize the definition of medication reviews and create a unified conceptual basis for their collaborative implementation and documentation in electronic patient records (definition appellation: collaborative medication review)., Methods: The study was conducted using the Delphi consensus survey with three interprofessional expert panel rounds in September-December 2020. The consensus rate was set at 80%. Experts assessed the proposed definition of collaborative medication review based on an international and national inventory of medication review definitions. The expert panel (n = 41) involved 12 physicians, 13 pharmacists, 10 nurses, and six information management professionals. The range of response rates for the rounds was 63-88%., Results: The experts commented on which of the pre-selected items (n = 75) characterizing medication reviews should be included in the definition of collaborative medication review. The items were divided into the following five themes and 51 of them reached consensus: 1) Actions included in the collaborative medication review (n = 24/24), 2) Settings where the review should be conducted (n = 5/5), 3) Situations where the review should be considered as needed and carried out (n = 10/11), 4) Prioritization of top five benefits to be achieved by the review and 5) Prioritization of top five patient groups to whom the review should be targeted., Conclusions: A strong interprofessional consensus was reached on the definition of collaborative medication review. The most challenging was to identify individual patient groups benefiting from the review., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest in their possible involvement in Alzheimer's disease (AD). Here we find that in the APdE9 and 5xFAD mouse models of AD, dural amyloid-β (Aβ) is confined to blood vessels and dLV morphology or function is not altered. The induction of sustained dLV atrophy or hyperplasia in the AD mice by blocking or overexpressing vascular endothelial growth factor C, impaired or improved, respectively, macromolecular cerebrospinal fluid (CSF) drainage to cervical lymph nodes. Yet, sustained manipulation of dLVs did not significantly alter the overall brain Aβ plaque load. Moreover, dLV atrophy did not alter the behavioral phenotypes of the AD mice, but it improved CSF-to-blood drainage. Our results indicate that sustained dLV manipulation does not affect Aβ deposition in the brain and that compensatory mechanisms promote CSF clearance., Competing Interests: Competing interests The authors declare no competing interests.

Deliberative democracy aims at reaching collective decisions through mechanisms that involve flexible opinions, variable alternative sets and information gathering in the process of decision making as opposed to exogenously fixed alternative sets and preference rankings. Deliberative democracy includes elements derived from bargaining and negotiation. Among its virtues, some proponents of deliberative democracy have included the possibility that several important negative results of the theory of voting can be avoided. The basic stratagem is to dismiss the universal domain condition typically assumed in social choice results. Thus, the validity of the results escaped from is obviously not in question. The position taken in this paper is that, while in some respects plausible, the escape argument is based on a too narrow view of the incompatibility results of the social choice theory. Some fundamental paradoxes remain beyond the reach of the deliberative techniques and are even exacerbated by them. That said, the deliberative approach can certainly be adopted for making voting alternatives more meaningful to those involved.

Branching morphogenesis is a ubiquitous process that gives rise to high exchange surfaces in the vasculature and epithelial organs. Lymphatic capillaries form branched networks, which play a key role in the circulation of tissue fluid and immune cells. Although mouse models and correlative patient data indicate that the lymphatic capillary density directly correlates with functional output, i.e., tissue fluid drainage and trafficking efficiency of dendritic cells, the mechanisms ensuring efficient tissue coverage remain poorly understood. Here, we use the mouse ear pinna lymphatic vessel network as a model system and combine lineage-tracing, genetic perturbations, whole-organ reconstructions and theoretical modeling to show that the dermal lymphatic capillaries tile space in an optimal, space-filling manner. This coverage is achieved by two complementary mechanisms: initial tissue invasion provides a non-optimal global scaffold via self-organized branching morphogenesis, while VEGF-C dependent side-branching from existing capillaries rapidly optimizes local coverage by directionally targeting low-density regions. With these two ingredients, we show that a minimal biophysical model can reproduce quantitatively whole-network reconstructions, across development and perturbations. Our results show that lymphatic capillary networks can exploit local self-organizing mechanisms to achieve tissue-scale optimization., (© 2023. Springer Nature Limited.)

The most common non-melanoma skin cancer is basal cell carcinoma (BCC). Surgery is the gold standard treatment but also non-surgical alternatives are needed. The purpose of this work was to present the early clinical experiences of degraded 4 MeV electron beam as a treatment method for superficial BCC. Twelve patients underwent two weeks radiation therapy treatment with either 5 × 7 Gy or 2 × 12 Gy. There were no significant differences in treatment outcome with different fractionations or lesion locations. The degraded beam method is a safe and valid non-surgical solution for suitable patients with superficial lesions., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Assi Valve has received research grant from Helsinki Cancer Center. Other authors have no conflict of interest to declare. All co-authors have seen and agree with the contents of the manuscript and there is no financial interest to report. We certify that the submission is original work and is not under review at any other publication.]., (© 2023 The Author(s).)

Aims: Cardiac energy metabolism is centrally involved in heart failure (HF), although the direction of the metabolic alterations is complex and likely dependent on the particular stage of HF progression. Vascular endothelial growth factor B (VEGF-B) has been shown to modulate metabolic processes and to induce physiological cardiac hypertrophy; thus, it could be cardioprotective in the failing myocardium. This study investigates the role of VEGF-B in cardiac proteomic and metabolic adaptation in HF during aldosterone and high-salt hypertensive challenges., Methods and Results: Male rats overexpressing the cardiac-specific VEGF-B transgene (VEGF-B TG) were treated for 3 or 6 weeks with deoxycorticosterone-acetate combined with a high-salt (HS) diet (DOCA + HS) to induce hypertension and cardiac damage. Extensive longitudinal echocardiographic studies of HF progression were conducted, starting at baseline. Sham-treated rats served as controls. To evaluate the metabolic alterations associated with HF, cardiac proteomics by mass spectrometry was performed. Hypertrophic non-treated VEGF-B TG hearts demonstrated high oxygen and adenosine triphosphate (ATP) demand with early onset of diastolic dysfunction. Administration of DOCA + HS to VEGF-B TG rats for 6 weeks amplified the progression from cardiac hypertrophy to HF, with a drastic drop in heart ATP concentration. Dobutamine stress echocardiographic analyses uncovered a significantly impaired systolic reserve. Mechanistically, the hallmark of the failing TG heart was an abnormal energy metabolism with decreased mitochondrial ATP, preceding the attenuated cardiac performance and leading to systolic HF., Conclusions: This study shows that the VEGF-B TG accelerates metabolic maladaptation which precedes structural cardiomyopathy in experimental hypertension and ultimately leads to systolic HF., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Most patients with idiopathic pulmonary fibrosis (IPF) complain of cough. IPF-associated cough is widely characterized as dry or non-productive. The aim of this study was to compare chronic cough in early stage IPF patients to cough in subjects with chronic cough from a community-based sample and, especially, to investigate whether cough in IPF is less productive than chronic cough in a community-based sample., Methods: The IPF cough population consisted of 46 biopsy-confirmed patients who complained of chronic cough. Control population consisted of subjects with chronic cough, gathered by a community-based email survey sent to public service employees and the Finnish Pensioners' Federation. A case-control setting was applied by having four age, gender, and smoking-status matched subjects from the community sample for each IPF cough patient. A cough specific quality of life questionnaire (Leicester Cough Questionnaire (LCQ)) was filled in by all subjects. The LCQ questionnaire contains 19 questions, each question is scored from 1 to 7 and total score from 3 to 21 with a smaller value indicating more severe impairment., Results: The sputum production frequency, as assessed by LCQ question 2, was 5.0 (3.0-6.0) in the IPF chronic cough population and 5.0 (3.0-6.0) in the community-based chronic cough population (median and interquartile range p= 0.72). The LCQ total score was 14.8 (11.5-18.1) in the IPF chronic cough population and 15.4 (13.0-17.5) in the community-based chronic cough population (p=0.76). The domain impact scores were physical, 4.9 (3.9-6.1) vs. 5.1 (4.5-5.6) (p=0.80); psychological, 4.6 (3.7-5.9) vs. 4.7 (3.9-5.7) (p=0.90); and social, 5.5 (3.7-6.5) vs. 5.5 (4.5-6.3) (p=0.84), respectively. Furthermore, cough response to paint or fumes, cough disturbing sleep, and cough frequency per day did not differ between the groups., Conclusion: Cough in early stage IPF patients was not distinguishable from chronic cough in the community-based population by LCQ. Especially, there was no difference in the self-reported frequency of cough-associated sputum production., (© 2023. The Author(s).)

The recent discovery of lymphatic vessels (LVs) in the dura mater, the outermost layer of meninges around the central nervous system (CNS), has opened a possibility for the development of alternative therapeutics for CNS disorders. The vascular endothelial growth factor C (VEGF-C)/VEGF receptor 3 (VEGFR3) signaling pathway is essential for the development and maintenance of dural LVs. However, its significance in mediating dural lymphatic function in CNS autoimmunity is unclear. We show that inhibition of the VEGF-C/VEGFR3 signaling pathway using a monoclonal VEGFR3-blocking antibody, a soluble VEGF-C/D trap, or deletion of the Vegfr3 gene in adult lymphatic endothelium causes notable regression and functional impairment of dural LVs but has no effect on the development of CNS autoimmunity in mice. During autoimmune neuroinflammation, the dura mater was only minimally affected, and neuroinflammation-induced helper T (T H ) cell recruitment, activation, and polarization were significantly less pronounced in the dura mater than in the CNS. In support of this notion, during autoimmune neuroinflammation, blood vascular endothelial cells in the cranial and spinal dura expressed lower levels of cell adhesion molecules and chemokines, and antigen-presenting cells (i.e., macrophages and dendritic cells) had lower expression of chemokines, MHC class II-associated molecules, and costimulatory molecules than their counterparts in the brain and spinal cord, respectively. The significantly weaker T H cell responses in the dura mater may explain why dural LVs do not contribute directly to CNS autoimmunity.

Background: We characterized the relation of primary treatment approaches to the need of later surgical interventions and the outcomes of patellar dislocation in patients with patellofemoral osteochondral fracture (OCF)., Methods: Overall, 134 patients with OCF were categorized in two groups according to treatment approach: primary surgery (operation within 90 days from injury) and conservative treatment. Data on surgical procedures, OCF characteristics, and patellofemoral anatomy were retrospectively collected. To measure subjective outcomes, 54 patients completed the knee-specific patient-reported outcome measures (PROMs) Kujala score, Tegner activity scale, the knee injury and osteoarthritis outcome score (KOOS) quality of life (QoL) subscale, and visual analog scale pain items., Results: The mean follow-up time was 4.9 years [standard deviation (SD) 2.7 years]. The primary treatment approach was surgery in 73 patients (54%) and conservative in 61 patients (46%) of whim 18 (30%) needed late surgery. Of primary surgery patients, the OCF was reimplanted in 45 patients (62%) and removed in the rest. Of all patients, 31 needed surgery in the later phase after the primary treatment approach (either reoperation or surgery after insufficient outcome of conservative treatment). In conservatively treated patients, OCF was smaller and patellofemoral joint malformation was more severe than in surgery group. Among patients who completed the PROMs, the outcomes appeared generally acceptable in both groups., Conclusions: Although a majority of the primary treatment approaches for OCF after patellar dislocation were definitive, one-fourth of patients required surgery in the later phase. PROMs did not indicate major differences between the study groups., (© 2023. The Author(s).)

The glycolipid transfer protein (GLTP) has been linked to many cellular processes aside from its best-known in vitro function as a lipid transport protein. It has been proposed to act as a sensor and regulator of glycosphingolipid homeostasis in cells. Furthermore, through its previously determined interaction with the endoplasmic reticulum membrane protein VAP-A (vesicle-associated membrane protein-associated protein A), GLTP may also be involved in facilitating vesicular transport in cells. In this study, we characterized the phenotype of CRISPR/Cas9-mediated GLTP KO HeLa cells. We showed that motility, three-dimensional growth, and cellular metabolism were all altered by GLTP knockout. Expression of a GLTP mutant incapable of binding VAP disrupted cell spheroid formation, indicating that the GLTP-VAP interaction is linked to cellular adhesion, cohesion, and three-dimensional growth. Most notably, we found evidence that GLTP, through its interaction with VAP-A, affects vesicular trafficking, marking the first cellular process discovered to be directly impacted by a change in GLTP expression., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Comorbidities are common and affect the prognosis of patients with interstitial lung diseases, but few previous studies have investigated patients with asbestosis., Methods: We collected comorbidities and death causes of 116 patients with asbestosis treated in Oulu University Hospital. Causes of death were confirmed by autopsy in 68% of the cases., Results: The most common comorbidities of asbestosis patients were pleural plaques (96%) and coronary artery disease (CAD; 67%). The prevalence of rheumatoid arthritis was 8.6%. The most common underlying causes of death were asbestosis (36%), CAD (24%), and lung cancer (LC) (10%). CAD and LC were associated with shorter survival in adjusted analyses., Conclusions: Patients with asbestosis have multiple comorbidities. Prevention and treatment of CAD and LC may influence the prognosis of asbestosis patients., Competing Interests: Conflict of Interest: The authors have the following competing interests that have not affected the contents of this study: E.K. reports congress/travel costs from Orion Pharma outside the submitted work and virtual congress cost from the University of Oulu Graduate School. J.S. reports congress/travel costs from Boehringer Ingelheim, GlaxoSmithKline, and Novartis Finland Oy, and lecturer's fees from Chiesi, all outside the submitted work. H.N. reports lecturer's fees from Boehringer Ingelheim Finland Ltd and Roche Ltd and congress/travel support from Boehringer-Ingelheim Ltd, Sanofi-Genzyme Ltd, Chiesi Ltd, and Duodecim, all outside the submitted work. R.K. has received virtual congress fee costs from Novartis and Roche, consulting fees from Boehringer-Ingelheim and MSD, and lecture fees from Roche and Boehringer-Ingelheim. H.V. declare no competing interests., (Copyright © 2022 American College of Occupational and Environmental Medicine.)

Multidisciplinary meeting (MDM) is a core element in the diagnosis of interstitial lung diseases (ILD). The aim of the study was to investigate the implementation and key elements related to ILD MDMs in Finnish specialized care, which is characterized by long travel distances and a large number of small centers treating patients suffering from ILDs. An electronic questionnaire was sent to ILD experts working at five academic centers of Finland regarding the implementation of ILD MDMs with the focus on utilization of virtual communication. Responses were received from all academic centers of Finland ( n  = 5) whose catchment areas cover all of Finland. ILD MDMs were organized in each center approximately every two weeks and the core participants included a radiologist, respiratory physicians, junior staff, pathologist and a rheumatologist. All non-academic centers could refer their patients to be evaluated in ILD MDM of an academic center. Virtual communication was utilized by all academic centers in the implementation of ILD MDMs, being most common among small centers located in Eastern and Northern Finland. Virtual access to ILD MDM of an academic center was available in most parts of Finland, enabling small centers to benefit from the ILD expertise of academic centers., Competing Interests: JS reports congress/travel costs from Boehringer Ingelheim, GlaxoSmithKline and Novartis Finland Oy, and lecturer’s fees from Chiesi, all outside the submitted work. HN reports grants for scientific work from the Foundation of the Finnish Anti-Tuberculosis Association and the North Savo Regional Fund of the Finnish Cultural Foundation, lecturers´ fees from Boehringer Ingelheim and Roche and congress/travel support from Boehringer-Ingelheim, Sanofi-Genzyme, Chiesi and Duodecim, all outside the submitted work. UH reports consulting and lecture fees from Johnson and Johnson and Boehringer Ingelheim, and congress travel costs from Chiesi and Roche. HH reports lecture fees from Boehringer Ingelheim and Chiesi, outside the submitted work. MK has nothing to disclose. MH reports lecture fees and payments for research purposes from Boehringer Ingelheim. MP reports personal lecture fee, congress travel costs and advisory board membership at Boehringer Ingelheim, lecture fee from Roche, congress travel cost from Orion Pharma, outside the submitted work. RK reports consulting and lecture fees from Boehringer Ingelheim, Roche and MSD, and virtual congress costs from Roche and Novartis., (© 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: The disease course of idiopathic pulmonary fibrosis (IPF) is progressive and occasionally, other types of interstitial lung disease (ILD) may progress similarly to IPF. This study aimed to evaluate risk factors for disease progression within 24 months in patients with various ILDs., Methods: This prospective study obtained 97 patients with a suspected ILD who underwent a transbronchial lung cryobiopsy. The extent of several high-resolution computed tomography (HRCT) patterns was assessed. Due to the inclusion criteria the study population presented a low extent of honeycombing and definite usual interstitial pneumonia (UIP) pattern on HRCT suggesting an early stage of ILD. Disease progression within 24 months despite treatment was defined as a relative decline of ≥ 10% in forced vital capacity (FVC), or a relative decline in FVC of ≥ 5% and one of the three additional criteria: (1) a decline in diffusion capacity to carbon monoxide (DLCO) ≥ 15%; (2) increased fibrosis on HRCT; (3) progressive symptoms, or progressive symptoms and increased fibrosis on HRCT. The same definition was utilized in patients with IPF and other ILDs. Risk factors for disease progression were evaluated in a multivariable logistic regression model., Results: Disease progression was revealed in 52% of the patients with ILD, 51% of the patients with IPF, and 53% of the patients with other types of ILD. A high extent of reticulation on HRCT (Odds ratio [OR] 3.11, 95% Confidence interval [CI] 1.21-7.98, P = 0.019) and never smoking (OR 3.11, CI 1.12-8.63, P = 0.029) were associated with disease progression whereas platelet count (OR 2.06 per 100 units increase, CI 0.96-4.45, P = 0.065) did not quite reach statistical significance., Conclusion: Higher extent of reticulation on HRCT and never smoking appeared to associate with the risk of disease progression within 24 months in ILD patients without honeycombing. Approximately half of the patients with ILD revealed disease progression, and similar proportions were observed in patients with IPF and in other types of ILD., (© 2022. The Author(s).)

Background: The use of a transbronchial lung cryobiopsy (TBLC) is increasing as a diagnostic method of interstitial lung diseases (ILD). This study aimed to evaluate risk factors associated with clinically significant complications of TBLC in ILD patients., Methods: Patients referred to Kuopio or Tampere university hospitals, in Finland, for a suspected ILD were included. The TBLC was performed in an outpatient setting for 100 patients. Patients were mechanically ventilated in general anesthesia. Fluoroscopy guidance and prophylactic bronchial balloon were used. Complications, such as bleeding, pneumothorax, infections, and mortality were recorded. Moderate or serious bleeding, pneumothorax, or death ≤90 days were defined as clinically significant complications. A multivariable model was created to assess clinically significant complications., Results: The extent of traction bronchiectasis (Odds ratio [OR] 1.30, Confidence interval [CI] 1.03-1.65, p = 0.027) and young age (OR 7.96, CI 2.32-27.3, p = 0.001) were associated with the risk of clinically significant complications whereas the use of oral corticosteroids ≤30 days before the TBLC (OR 3.65, CI 0.911-14.6, p = 0.068) did not quite reach statistical significance. A history of serious cough was associated with the risk of pneumothorax (OR 4.18, CI 1.10-16.0, p = 0.036). Procedure associated mortality ≤90 days was 1%., Conclusion: The extent of traction bronchiectasis on HRCT and young age were associated with the risk of clinically significant complications whereas oral corticosteroid use did not quite reach statistical significance. A history of serious cough was associated with the risk of clinically significant pneumothorax., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the pharmacokinetics of orally and intravenously (IV) administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus)., Study Design: A crossover design with an 11 day washout period., Animals: A total of eight young male reindeer, aged 1.5-2.5 years and weighing 74.3 ± 6.3 kg, mean ± standard deviation., Methods: The reindeer were administered meloxicam (0.5 mg kg -1 IV or orally). Blood samples were repeatedly collected from the jugular vein for up to 72 hours post administration. Plasma samples were analysed for meloxicam concentrations with ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry. Noncompartmental analysis for determination of pharmacokinetic variables was performed., Results: The pharmacokinetic values, median (range), were determined. Elimination half-life (t ½ ) with the IV route (n = 4) was 15.2 (13.2-16.8) hours, the volume of distribution at steady state was 133 (113-151) mL kg -1 and clearance was 3.98 (2.63-5.29) mL hour -1 kg -1 . After oral administration (n = 7), the peak plasma concentration (C max ) was detected at 6 hours, t ½ was 19.3 (16.7-20.5) hours, C max 1.82 (1.17-2.78) μg mL -1 and bioavailability (n = 3) 49 (46-73)%. No evident adverse effects were detected after either administration route., Conclusions and Clinical Relevance: A single dose of meloxicam (0.5 mg kg -1 IV or orally) has the potential to maintain the therapeutic concentration determined in other species for up to 3 days in reindeer plasma., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: We examine the outcomes following operative treatment of intra-articular fracture combined with medial patellofemoral ligament (MPFL) reconstruction after patella dislocation., Methods: Patients were retrospectively identified from medical records using diagnostic and surgical procedure codes. Radiological anatomical parameters and bony abnormalities of injured knees were assessed from magnetic resonance images (MRI). Inclusion criteria were traumatic patellar dislocation with chondral or osteochondral fracture and MPFL rupture, operative treatment of a chondral or osteochondral fracture combined with MPFL reconstruction, and minimum follow-up of 2 years. Outcomes were measured using the Kujala score, Tegner activity scale, and the Knee injury and Osteoarthritis Outcome Score Quality-of-Life subscale (KOOS-QLS)., Results: During 2012 and 2015, 322 patients were treated because of patellar dislocation. Thirty-three patients had chondral or osteochondral fracture. Eleven patients (five males and six females) with a mean [standard deviation (SD)] age of 17.0 (6.5) years at the time of surgery met the inclusion criteria and were included. Five of the 11 patients had a subchondral and six an osteochondral fracture. Eight patients had a fracture in the patella and three in the femur. All patients had bony abnormalities in the knee. Nine out of 11 patients scored over 90/100 points on the Kujala scale and had good results on the Tegner scale [before surgery 5.0 (2.7) points versus after surgery 5.3 (1.6) points] and the KOOS-QLS [4.1 (4.2) points] outcome measures., Conclusion: The removal or fixation of the fracture fragment combined with MPFL reconstruction is a feasible option in the treatment of symptomatic osteochondral or subchondral fragment in traumatic patellar dislocation. The short-term outcomes are encouraging., Level of Evidence: Level IV, retrospective case series., (© 2022. The Author(s).)

Objective: The aim of this study was to compare the clinical outcome of cartilage repair with autologous chondrocyte implantation (ACI) in patients with osteochondritis dissecans (OCD) lesions and full-thickness cartilage lesions., Design: This study included a cohort of 115 consecutive patients with a cartilage lesion of the knee treated with ACI. Of the patients, 35 had an OCD lesion and 80 a full-thickness cartilage lesion. During a follow-up period from 2 to 13 years all treatment failures were identified. The failure rate between OCD lesions and full-thickness cartilage lesions was compared with Kaplan-Meier analysis. Patient-reported outcome was evaluated 2 years postoperatively with the Lysholm score., Results: During the follow-up 21 out of 115 patients encountered a treatment failure. The failure rate for full-thickness cartilage lesions was 19.1% and for OCD lesions 43.3% over the 10-year follow-up. Patient-reported outcome improved from baseline to 2 years postoperatively. The improvement from baseline was statistically significant, and the Lysholm score improved more than the minimal clinically important difference. The patient-reported outcome showed no difference between lesion types at 2 years., Conclusions: In the presented retrospective study, the failure rate of first-generation ACI was higher in OCD lesions than in large full-thickness cartilage lesions, suggesting that OCD lesions may associate with properties that affect the durability of repair tissue. Future prospective studies are needed to tell us how to best repair OCD lesions with biological tissue engineering.

Purpose: Despite the comprehensive literature on the anatomical risk factors for patellar dislocation, knowledge on the risk factors for subsequent osteochondral fracture (OCF) remains limited., Methods: Magnetic resonance imaging was used to compare measures of patellofemoral anatomy in patients with OCF after patellar dislocation and propensity score matched patients without OCF. For differing measures, limit values showing a 50% probability for the occurrence of OCF were calculated using predictive logistic regression modelling. Proportions of abnormal measures in the groups were compared using Chi-square test. The association of anatomical measures with OCF location was examined by comparing subgroup mean values in the different OCF locations., Results: Propensity score matching provided a total of 111 matched pairs of patients with OCF and patients without OCF. The patients with and without OCF differed in patellotrochlear index (PTI; 0.54 [95% CI 0.52-0.57] vs. 0.47 [95% CI 0.45-0.49]; p < 0.001), tibial tubercle-posterior cruciate ligament distance (TT-PCL; 21.6 mm [95% CI 21.0-22.3 mm] vs. 20.5 mm [95% CI 20.0-21.1 mm]; p = 0.013), trochlear depth (2.5 mm [95% CI 2.3-2.7 mm] vs. 3.0 mm [95% CI 2.8-3.2 mm]; p < 0.001) trochlear facet asymmetry ratio (0.54 [95% CI 0.51-0.57] vs. 0.43 [95% CI 0.42-0.45]; p < 0.001) and trochlear condyle asymmetry ratio (1.04 [95% CI 1.03-1.04] vs. 1.05 [95% CI 1.04-1.05]; 0.013. Thresholds for increased OCF risk were > 0.51 for PTI  > 21.1 mm for TT-PCL < 2.8 mm for trochlear depth > 0.48 for trochlear facet asymmetry ratio and < 1.04 for trochlear condyle asymmetry ratio., Conclusion: In patients with OCF after patellar dislocation, trochlear configuration and patella vertical location were closer to normal anatomy, whereas patella lateralization was more severe when compared to patients without OCF. These anatomical factors contribute to the risk of OCF during patellar dislocation., Level of Evidence: III., (© 2021. European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Objective . This study aims to describe biomechanical maturation process of repair tissue after cartilage repair with autologous chondrocyte implantation (ACI) at long-term follow-up. Design . After ACI, 40 patients underwent altogether 60 arthroscopic biomechanical measurements of the repair tissue at various time points during an up to 11-year follow-up period. Of these patients, 30 patients had full-thickness cartilage lesions and 10 had an osteochondritis dissecans (OCD) defect. The mean lesion area was 6.5 cm 2 (SD 3.2). A relative indentation stiffness value for each individually measured lesion was calculated as a ratio of repair tissue and surrounding cartilage indentation value to enable interindividual comparison. Results . Repair tissue stiffness improved during approximately 5 years after surgery. Most of the increase in stiffness occurred during the first 2 years. The curvilinear correlation between relative stiffness values and the follow-up time was 0.31 (95% CI 0.07-0.52), P = 0.017. The interindividual variation of the stiffness was high. Lesion properties or demographic factors showed no significant correlation to biomechanical outcome. The overall postoperative average relative stiffness was 0.75 (SD 0.47). Conclusions . Our clinical study describes a biomechanical maturation process of cartilage repair that may continue even longer than expected. A substantial increase in tissue stiffness proceeds for the first two years postoperatively. Minor progression proceeds for even longer. In some repairs, the biomechanical result was equal to native cartilage, suggesting hyaline-type repair. The variation in biomechanical results suggests substantial inconsistency in the structural outcome following ACI.