Specimen collection is essential for modern science.

Natural history museums are vital repositories of specimens, samples and data that inform about the natural world; this Formal Comment revisits a Perspective that advocated for the adoption of compassionate collection practices, querying whether it will ever be possible to completely do away with whole animal specimen collection.

Infections and their prognostic significance before diagnosis of chronic lymphocytic leukemia, non-Hodgkin lymphoma, or multiple myeloma.

BACKGROUND: Immunodeficiency is a shared feature of B cell malignancies. The risk of infections and their prognostic significance after diagnosis are well characterized, but, conversely, less is known about prediagnostic infections in these domains. METHODS: In matched case-control analyzes, using Danish nationwide registers, we assessed the rate of prediagnostic infections in chronic lymphocytic leukemia (CLL), diffuse large B cell lymphoma (DLBCL), multiple myeloma (MM), follicular lymphoma (FL), marginal zone lymphoma (MZL), and lymphoplasmacytic lymphoma (LPL). Survival analyzes of data from clinical registers were then used to determine the effect of infections in the year preceding diagnosis on overall survival. To yield results for as many patients as possible, antimicrobial prescriptions were used as surrogates for infections. RESULTS: The nationwide and clinical registers comprised 30,389 patients, accumulating 213,649 antimicrobial prescriptions, and 18,560 patients accumulating 107,268 prescriptions, respectively. The relative risk of infections was increased up to 15 years prior to diagnosis of malignancy and markedly increased in the year just prior to diagnosis. More than two antimicrobials within one year prior to diagnosis were associated with significantly shorter overall survival, independently of known prognostic factors. CONCLUSION: Patients with B cell-derived malignancies exhibit marked immunodeficiency several years prior to diagnosis such that different disease subtypes demonstrate both overlapping and distinct trends in infection risk preceding diagnosis. Moreover, multiple infections within the year preceding diagnosis are independently associated with shorter overall survival for all the examined malignancies.

Risk of hypersensitivity pneumonitis and other interstitial lung diseases following organic dust exposure.

BACKGROUND: Organic dust is associated with hypersensitivity pneumonitis, and associations with other types of interstitial lung disease (ILD) have been suggested. We examined the association between occupational organic dust exposure and hypersensitivity pneumonitis and other ILDs in a cohort study. METHODS: The study population included all residents of Denmark born in 1956 or later with at least 1 year of gainful employment since 1976. Incident cases of hypersensitivity pneumonitis and other ILDs were identified in the Danish National Patient Register 1994-2015. Job exposure matrices were used to assign individual annual levels of exposure to organic dust, endotoxin and wood dust from 1976 to 2015. We analysed exposure-response relations by different exposure metrics using a discrete-time hazard model. RESULTS: For organic dust, we observed increasing risk with increasing cumulative exposure with incidence rate ratios (IRR) per 10 unit-years of 1.19 (95% CI 1.12 to 1.27) for hypersensitivity pneumonitis and 1.04 (95% CI 1.02 to 1.06) for other ILDs. We found increasing risk with increasing cumulative endotoxin exposure for hypersensitivity pneumonitis and other ILDs with IRRs per 5000 endotoxin units/m3-years of 1.55 (95% CI 1.38 to 1.73) and 1.09 (95% CI 1.00 to 1.19), respectively. For both exposures, risk also increased with increasing duration of exposure and recent exposure. No increased risks were observed for wood dust exposure. CONCLUSION: Exposure-response relations were observed between organic dust and endotoxin exposure and hypersensitivity pneumonitis and other ILDs, with lower risk estimates for the latter. The findings indicate that organic dust should be considered a possible cause of any ILD. TRIAL REGISTRATION NUMBER: j.no.: 1-16-02-196-17.

Using AI to Identify Unremarkable Chest Radiographs for Automatic Reporting.

Background Radiology practices have a high volume of unremarkable chest radiographs and artificial intelligence (AI) could possibly improve workflow by providing an automatic report. Purpose To estimate the proportion of unremarkable chest radiographs, where AI can correctly exclude pathology (ie, specificity) without increasing diagnostic errors. Materials and Methods In this retrospective study, consecutive chest radiographs in unique adult patients (≥18 years of age) were obtained January 1-12, 2020, at four Danish hospitals. Exclusion criteria included insufficient radiology reports or AI output error. Two thoracic radiologists, who were blinded to AI output, labeled chest radiographs as "remarkable" or "unremarkable" based on predefined unremarkable findings (reference standard). Radiology reports were classified similarly. A commercial AI tool was adapted to output a chest radiograph "remarkableness" probability, which was used to calculate specificity at different AI sensitivities. Chest radiographs with missed findings by AI and/or the radiology report were graded by one thoracic radiologist as critical, clinically significant, or clinically insignificant. Paired proportions were compared using the McNemar test. Results A total of 1961 patients were included (median age, 72 years [IQR, 58-81 years]; 993 female), with one chest radiograph per patient. The reference standard labeled 1231 of 1961 chest radiographs (62.8%) as remarkable and 730 of 1961 (37.2%) as unremarkable. At 99.9%, 99.0%, and 98.0% sensitivity, the AI had a specificity of 24.5% (179 of 730 radiographs [95% CI: 21, 28]), 47.1% (344 of 730 radiographs [95% CI: 43, 51]), and 52.7% (385 of 730 radiographs [95% CI: 49, 56]), respectively. With the AI fixed to have a similar sensitivity as radiology reports (87.2%), the missed findings of AI and reports had 2.2% (27 of 1231 radiographs) and 1.1% (14 of 1231 radiographs) classified as critical (P = .01), 4.1% (51 of 1231 radiographs) and 3.6% (44 of 1231 radiographs) classified as clinically significant (P = .46), and 6.5% (80 of 1231) and 8.1% (100 of 1231) classified as clinically insignificant (P = .11), respectively. At sensitivities greater than or equal to 95.4%, the AI tool exhibited less than or equal to 1.1% critical misses. Conclusion A commercial AI tool used off-label could correctly exclude pathology in 24.5%-52.7% of all unremarkable chest radiographs at greater than or equal to 98% sensitivity. The AI had equal or lower rates of critical misses than radiology reports at sensitivities greater than or equal to 95.4%. These results should be confirmed in a prospective study. © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Yoon and Hwang in this issue.

Occupational exposure to respirable crystalline silica and incident idiopathic interstitial pneumonias and pulmonary sarcoidosis: a national prospective follow-up study.

BACKGROUND: Respirable crystalline silica is a well-known cause of silicosis but may also be associated with other types of interstitial lung disease. We examined the associations between occupational exposure to respirable crystalline silica and the risk of idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. METHODS: The total Danish working population was followed 1977-2015. Annual individual exposure to respirable crystalline silica was estimated using a quantitative job exposure matrix. Cases were identified in the Danish National Patient Register. We conducted adjusted analyses of exposure-response relations between cumulative silica exposure and other exposure metrics and idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. RESULTS: Mean cumulative exposure was 125 µg/m3-years among exposed workers. We observed increasing incidence rate ratios with increasing cumulative silica exposure for idiopathic interstitial pneumonias, pulmonary sarcoidosis and silicosis. For idiopathic interstitial pneumonias and pulmonary sarcoidosis, trends per 50 µg/m3-years were 1.03 (95% CI 1.02 to 1.03) and 1.06 (95% CI 1.04 to 1.07), respectively. For silicosis, we observed the well-known exposure-response relation with a trend per 50 µg/m3-years of 1.20 (95% CI 1.17 to 1.23). CONCLUSION: This study suggests that silica inhalation may be related to pulmonary sarcoidosis and idiopathic interstitial pneumonias, though these findings may to some extent be explained by diagnostic misclassification. The observed exposure-response relations for silicosis at lower cumulative exposure levels than previously reported need to be corroborated in analyses that address the limitations of this study.

Extraordinary levels of per- and polyfluoroalkyl substances (PFAS) in vertebrate animals at a New Mexico desert oasis: Multiple pathways for wildlife and human exposure.

Per- and polyfluoroalkyl substances (PFAS) in the environment pose persistent and complex threats to human and wildlife health. Around the world, PFAS point sources such as military bases expose thousands of populations of wildlife and game species, with potentially far-reaching implications for population and ecosystem health. But few studies shed light on the extent to which PFAS permeate food webs, particularly ecologically and taxonomically diverse communities of primary and secondary consumers. Here we conducted >2000 assays to measure tissue-concentrations of 17 PFAS in 23 species of mammals and migratory birds at Holloman Air Force Base (AFB), New Mexico, USA, where wastewater catchment lakes form biodiverse oases. PFAS concentrations were among the highest reported in animal tissues, and high levels have persisted for at least three decades. Twenty of 23 species sampled at Holloman AFB were heavily contaminated, representing middle trophic levels and wetland to desert microhabitats, implicating pathways for PFAS uptake: ingestion of surface water, sediments, and soil; foraging on aquatic invertebrates and plants; and preying upon birds or mammals. The hazardous long carbon-chain form, perfluorooctanosulfonic acid (PFOS), was most abundant, with liver concentrations averaging >10,000 ng/g wet weight (ww) in birds and mammals, respectively, and reaching as high 97,000 ng/g ww in a 1994 specimen. Perfluorohexanesulfonic acid (PFHxS) averaged thousands of ng/g ww in the livers of aquatic birds and littoral-zone house mice, but one order of magnitude lower in the livers of upland desert rodent species. Piscivores and upland desert songbirds were relatively uncontaminated. At control sites, PFAS levels were strikingly lower on average and different in composition. In sum, legacy PFAS at this desert oasis have permeated local aquatic and terrestrial food webs across decades, severely contaminating populations of resident and migrant animals, and exposing people via game meat consumption and outdoor recreation.

Opioids and personalized analgesia in the perioperative setting: A protocol for five systematic reviews.

BACKGROUND: Treatment with opioids is a mainstay in perioperative pain management. While the leading treatment paradigm has been procedure-specific pain management, efforts regarding personalized pain treatment are increasing. The OPI•AID project aims to develop personalized algorithms for perioperative pain management, taking demographic, surgical, and anaesthesiologic factors into account. We will undertake five parallel reviews to illuminate current evidence on different aspects of individual responses to perioperative opioid treatment. METHODS: Inclusion of adult populations in English-written studies. Review-specific searches are developed for the following databases: CENTRAL, MEDLINE, Embase, clinicaltrials.gov, and clinicaltrial.eu. Two authors will independently screen citations, extract data, and assess the risks of bias in each review (QUIPS, PROBAST and RoB2, as relevant). CONCLUSION: These reviews will evaluate various aspects of perioperative opioid treatment, including individualized treatment strategies, selection of specific opioids, and individual patient responses. These will guide future development of a personalized perioperative opioid treatment algorithm (OPI•AID) that will be validated and tested clinically against standard of care.

Consequences of Losing Incidental Pulmonary Nodules to Follow-Up: Unmonitored Nodules Progressing to Stage IV Lung Cancer.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death globally. Incidental pulmonary nodules represent a golden opportunity for early diagnosis, which is critical for improving survival rates. This study explores the impact of missed pulmonary nodules on the progression of lung cancer. METHODS: A total of 4,066 stage IV lung cancer cases from 2019 to 2021 in Danish hospitals were investigated to determine whether a chest computed tomography (CT) had been performed within 2 years before diagnosis. CT reports and images were reviewed to identify nodules that had been missed by radiologists or were not appropriately monitored, despite being mentioned by the radiologist, and to assess whether these nodules had progressed to stage IV lung cancer. RESULTS: Among stage IV lung cancer patients, 13.6% had undergone a chest CT scan before their diagnosis; of these, 44.4% had nodules mentioned. Radiologists missed a nodule in 7.6% of cases. In total, 45.3% of nodules were not appropriately monitored. An estimated 2.5% of stage IV cases could have been detected earlier with proper surveillance. CONCLUSION: This study underlines the significance of monitoring pulmonary nodules and proposes strategies for enhancing detection and surveillance. These strategies include centralized monitoring and the implementation of automated registries to prevent gaps in follow-up.

Evaluation of an Unloading Concept for Knee Osteoarthritis: A Pilot Study in a Small Patient Group.

Joint compressive forces have been identified as a risk factor for osteoarthritis disease progression. Therefore, unloader braces are a common treatment with the aim of relieving pain, but their effects are not clearly documented in the literature. A knee brace concept was tested with the aim of reducing joint loads and pain in knee osteoarthritis patients by applying an extension moment exclusively during the stance phase. The ideal effects were evaluated during gait based on musculoskeletal modeling of six patients, and experimental tests with a prototype brace were conducted on one patient. The effects were evaluated using electromyography measurements and musculoskeletal models to evaluate the muscle activation and knee compressive forces, respectively. The ideal brace simulations revealed a varying reduction of the first peak knee force between 3.5% and 33.8% across six patients whereas the second peak was unaffected. The prototype reduced the peak vasti muscle activation with 7.9% and musculoskeletal models showed a reduction of the first peak knee compressive force of up to 26.3%. However, the prototype brace increased the knee joint force impulse of up to 17.1% and no immediate pain reduction was observed. The reduction of the first peak knee compressive force, using a prototype on a single patient, indicates a promising effect from an applied knee extension moment for reducing knee joint loads during normal gait. However, further clinical experiments with this brace method are required to evaluate the long-term effects on both pain and disease progression in knee osteoarthritis patients.

Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia.

For chronic lymphocytic leukaemia (CLL), targeted drugs have become the standard of care, in particular for second-line treatment. In this study, overall survival (OS), treatment-free survival (TFS) and adverse events (AE) were registered retrospectively in a Danish population-based cohort upon second-line treatment for CLL. Data were collected from medical records and the Danish National CLL register. For 286 patients receiving second-line treatment, three-year TFS was higher upon targeted treatment (ibrutinib/venetoclax/idelalisib) [63%, 95% confidence interval (CI) 50%-76%] compared with fludarabine, cyclophosphamide and rituximab or bendamustine and rituximab (FCR/BR) (37%, CI: 26%-48%) and chlorambucil+/-CD20-antibody (CD20Clb/Clb) (22%, CI: 10%-33%). Upon targeted treatment, three-year OS estimates were higher for targeted treatment (79%, CI: 68%-91%) compared with FCR/BR (70%, CI: 60%-81%) or CD20Clb/Clb (60%, CI: 47%-74%). The most common AEs were infections and haematological AEs; 92% of patients treated with targeted drugs had AEs, 53% of which were severe. Upon FCR/BR and CD20Clb/Clb, AEs were present for 75% and 53% respectively, of which 63% and 31% were severe. These real-world data demonstrate higher TFS and a tendency towards higher OS following targeted second-line treatment for CLL compared to chemoimmunotherapy, also for patients who may be frailer and more comorbid.

Commercially Available Chest Radiograph AI Tools for Detecting Airspace Disease, Pneumothorax, and Pleural Effusion.

Background Commercially available artificial intelligence (AI) tools can assist radiologists in interpreting chest radiographs, but their real-life diagnostic accuracy remains unclear. Purpose To evaluate the diagnostic accuracy of four commercially available AI tools for detection of airspace disease, pneumothorax, and pleural effusion on chest radiographs. Materials and Methods This retrospective study included consecutive adult patients who underwent chest radiography at one of four Danish hospitals in January 2020. Two thoracic radiologists (or three, in cases of disagreement) who had access to all previous and future imaging labeled chest radiographs independently for the reference standard. Area under the receiver operating characteristic curve, sensitivity, and specificity were calculated. Sensitivity and specificity were additionally stratified according to the severity of findings, number of findings on chest radiographs, and radiographic projection. The χ2 and McNemar tests were used for comparisons. Results The data set comprised 2040 patients (median age, 72 years [IQR, 58-81 years]; 1033 female), of whom 669 (32.8%) had target findings. The AI tools demonstrated areas under the receiver operating characteristic curve ranging 0.83-0.88 for airspace disease, 0.89-0.97 for pneumothorax, and 0.94-0.97 for pleural effusion. Sensitivities ranged 72%-91% for airspace disease, 63%-90% for pneumothorax, and 62%-95% for pleural effusion. Negative predictive values ranged 92%-100% for all target findings. In airspace disease, pneumothorax, and pleural effusion, specificity was high for chest radiographs with normal or single findings (range, 85%-96%, 99%-100%, and 95%-100%, respectively) and markedly lower for chest radiographs with four or more findings (range, 27%-69%, 96%-99%, 65%-92%, respectively) (P < .001). AI sensitivity was lower for vague airspace disease (range, 33%-61%) and small pneumothorax or pleural effusion (range, 9%-94%) compared with larger findings (range, 81%-100%; P value range, > .99 to < .001). Conclusion Current-generation AI tools showed moderate to high sensitivity for detecting airspace disease, pneumothorax, and pleural effusion on chest radiographs. However, they produced more false-positive findings than radiology reports, and their performance decreased for smaller-sized target findings and when multiple findings were present. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Yanagawa and Tomiyama in this issue.

Autonomous Chest Radiograph Reporting Using AI: Estimation of Clinical Impact.

Background Automated interpretation of normal chest radiographs could alleviate the workload of radiologists. However, the performance of such an artificial intelligence (AI) tool compared with clinical radiology reports has not been established. Purpose To perform an external evaluation of a commercially available AI tool for (a) the number of chest radiographs autonomously reported, (b) the sensitivity for AI detection of abnormal chest radiographs, and (c) the performance of AI compared with that of the clinical radiology reports. Materials and Methods In this retrospective study, consecutive posteroanterior chest radiographs from adult patients in four hospitals in the capital region of Denmark were obtained in January 2020, including images from emergency department patients, in-hospital patients, and outpatients. Three thoracic radiologists labeled chest radiographs in a reference standard based on chest radiograph findings into the following categories: critical, other remarkable, unremarkable, or normal (no abnormalities). AI classified chest radiographs as high confidence normal (normal) or not high confidence normal (abnormal). Results A total of 1529 patients were included for analysis (median age, 69 years [IQR, 55-69 years]; 776 women), with 1100 (72%) classified by the reference standard as having abnormal radiographs, 617 (40%) as having critical abnormal radiographs, and 429 (28%) as having normal radiographs. For comparison, clinical radiology reports were classified based on the text and insufficient reports excluded (n = 22). The sensitivity of AI was 99.1% (95% CI: 98.3, 99.6; 1090 of 1100 patients) for abnormal radiographs and 99.8% (95% CI: 99.1, 99.9; 616 of 617 patients) for critical radiographs. Corresponding sensitivities for radiologist reports were 72.3% (95% CI: 69.5, 74.9; 779 of 1078 patients) and 93.5% (95% CI: 91.2, 95.3; 558 of 597 patients), respectively. Specificity of AI, and hence the potential autonomous reporting rate, was 28.0% of all normal posteroanterior chest radiographs (95% CI: 23.8, 32.5; 120 of 429 patients), or 7.8% (120 of 1529 patients) of all posteroanterior chest radiographs. Conclusion Of all normal posteroanterior chest radiographs, 28% were autonomously reported by AI with a sensitivity for any abnormalities higher than 99%. This corresponded to 7.8% of the entire posteroanterior chest radiograph production. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Park in this issue.

Mitonuclear discordance results from incomplete lineage sorting, with no detectable evidence for gene flow, in a rapid radiation of Todiramphus kingfishers.

Many organisms possess multiple discrete genomes (i.e. nuclear and organellar), which are inherited separately and may have unique and even conflicting evolutionary histories. Phylogenetic reconstructions from these discrete genomes can yield different patterns of relatedness, a phenomenon known as cytonuclear discordance. In many animals, mitonuclear discordance (i.e. discordant evolutionary histories between the nuclear and mitochondrial genomes) has been widely documented, but its causes are often considered idiosyncratic and inscrutable. We show that a case of mitonuclear discordance in Todiramphus kingfishers can be explained by extensive genome-wide incomplete lineage sorting (ILS), likely a result of the explosive diversification history of this genus. For these kingfishers, quartet frequencies reveal that the nuclear genome is dominated by discordant topologies, with none of the internal branches in our consensus nuclear tree recovered in >50% of genome-wide gene trees. Meanwhile, a lack of inter-species shared ancestry, non-significant pairwise tests for gene flow, and little evidence for meaningful migration edges between species, leads to the conclusion that gene flow cannot explain the mitonuclear discordance we observe. This lack of evidence for gene flow combined with evidence for extensive genome-wide gene tree discordance, a hallmark of ILS, leads us to conclude that the mitonuclear discordance we observe likely results from ILS, specifically deep coalescence of the mitochondrial genome. Based on this case study, we hypothesize that similar demographic histories in other 'great speciator' taxa across the Indo-Pacific likely predispose these groups to high levels of ILS and high likelihoods of mitonuclear discordance.

Wallacean and Melanesian Islands Promote Higher Rates of Diversification within the Global Passerine Radiation Corvides.

The complex island archipelagoes of Wallacea and Melanesia have provided empirical data behind integral theories in evolutionary biology, including allopatric speciation and island biogeography. Yet, questions regarding the relative impact of the layered biogeographic barriers, such as deep-water trenches and isolated island systems, on faunal diversification remain underexplored. One such barrier is Wallace's Line, a significant biogeographic boundary that largely separates Australian and Asian biodiversity. To assess the relative roles of biogeographic barriers-specifically isolated island systems and Wallace's Line-we investigated the tempo and mode of diversification in a diverse avian radiation, Corvides (Crows and Jays, Birds-of-paradise, Vangas, and allies). We combined a genus-level data set of thousands of ultraconserved elements (UCEs) and a species-level, 12-gene Sanger sequence matrix to produce a well-resolved supermatrix tree that we leveraged to explore the group's historical biogeography and the effects of the biogeographic barriers on their macroevolutionary dynamics. The tree is well resolved and differs substantially from what has been used extensively for past comparative analyses within this group. We confirmed that Corvides, and its major constituent clades, arose in Australia and that a burst of dispersals west across Wallace's Line occurred after the uplift of Wallacea during the mid-Miocene. We found that dispersal across this biogeographic barrier was generally rare, though westward dispersals were two times more frequent than eastward dispersals. Wallacea's central position between Sundaland and Sahul no doubt acted as a bridge for island-hopping dispersal out of Australia, across Wallace's Line, to colonize the rest of Earth. In addition, we found that the complex island archipelagoes east of Wallace's Line harbor the highest rates of net diversification and are a substantial source of colonists to continental systems on both sides of this biogeographic barrier. Our results support emerging evidence that island systems, particularly the geologically complex archipelagoes of the Indo-pacific, are drivers of species diversification. [Historical biogeography; island biogeography; Melanesia; molecular phylogenetics; state-dependent diversification and extinction.].

Impact of type 2 diabetes on mortality, cause of death, and treatment in chronic lymphocytic leukemia.

Age-related comorbid conditions are exceedingly common in patients with chronic lymphocytic leukemia (CLL). As the prevalence of type 2 diabetes (T2D) is predicted to double during the next two decades, a better understanding of the interplay between CLL and T2D is of increasing importance. In this study, analyses were performed in parallel in two separate cohorts, based on Danish national registers and the Mayo Clinic CLL Resource. The primary outcomes were overall survival (OS) from time of CLL diagnosis, OS from time of treatment, and time to first treatment (TTFT), studied using Cox proportional hazard regression analysis and Fine-Gray regression analysis. In the Danish CLL cohort, the prevalence of T2D was 11%, in the Mayo CLL cohort, it was 12%. Patients with CLL and T2D had shorter OS both from time of diagnosis and from first-line treatment for were less likely to receive treatment for CLL compared with patients with CLL and without T2D. The increased mortality was largely driven by an increased risk of death due to infections, especially in the Danish cohort. The findings of this study emphasize a substantial subgroup of CLL patients with co-occurring T2D with an inferior prognosis and a possible unmet treatment need requiring additional interventions and further research.

Increased incidence rates of positive blood cultures shortly after chemotherapy compared to radiotherapy among individuals treated for solid malignant tumours.

BACKGROUND: Cancer treatments suppress immune function and are associated with increased risk of infections, but the overall burden of serious infectious diseases in treated patients has not been clearly elucidated. METHODS: All patients treated for solid malignant tumours with radiotherapy (RT) and/or standard first-line chemotherapy (C) at the Department of Oncology at Rigshospitalet between 01/1/2010 and 31/12/2016 were included. Patients were followed from treatment initiation until the first of new cancer treatment, 1 year after treatment initiation, end of follow-up or death. Incidence rates (IR) of positive blood culture (PBC) per 1000 person-years follow-up (PYFU) were calculated. FINDINGS: 12,433 individuals were included, 3582 (29%), 6349 (51%), and 2502 (20%) treated with RT, C, or both RT & C, respectively, contributing 8182 PYFU. 429 (3%) individuals experienced 502 unique episodes of PBC, incidence rate (95% CI) 52.43 (47.7, 57.6) per 1000 PYFU. The 30-day mortality rate after PBC was 24% independent of treatment modality. Adjusted incidence rate ratios in the first 3 months (95% CI) after PBC significantly varied by treatment: 2.89 (1.83, 4.55) and 2.52 (1.53, 4.14) for C and RT & C compared to RT. Escherichia coli (n = 127, 25%) was the top microorganism identified. INTERPRETATION: PBCs are not common, but when they occur, mortality is high.

The usual Interstitial pneumonia pattern in autoimmune rheumatic diseases.

Usual Interstitial Pneumonia (UIP) is characterized by progression of lung parenchyma that may be observed in various autoimmune rheumatic diseases (ARDs), including rheumatoid arthritis and connective tissue diseases. From a diagnostic point of view, a UIP pattern related to ARDs may display imaging and pathological features able to distinguish it from that related to IPF, such as the "straight-edge" sign at HRCT and lymphoplasmacytic infiltrates at histologic specimens. Multidisciplinary approach (MDD), involving at least pulmonologist, rheumatologist and radiologist, is fundamental in the differential diagnosis process, but MDD is also required in the evaluation of severity, progression and response to treatment, that is based on the combination of changes in symptoms, pulmonary function trends, and, in selected patients, serial CT evaluation. Differently from IPF, in patients with ARDs both functional evaluation and patient-reported outcomes may be affected by systemic involvement and comorbidities, including musculoskeletal manifestations of disease. Finally, in regards to pharmacological treatment, immunosuppressants have been considered the cornerstone of therapy, despite the lack of solid evidence in most cases; recently, antifibrotic drugs were also proposed for the treatment of progressive fibrosing ILDs other than IPF. In ARD-ILD, the therapeutic choice should balance the need for the control of systemic and lung involvements with the risk of adverse events from multi-morbidities and -therapies. Purpose of this review is to summarize the definition, the radiological and morphological features of the UIP pattern in ARDs, together with risk factors, diagnostic criteria, prognostic evaluation, monitoring and management approaches of the UIP-ARDs.

Simulated Increase in Monoarticular Hip Muscle Strength Reduces the First Peak of Knee Compression Forces During Walking.

Reducing compressive knee contact forces (KCF) during walking could slow the progression and reduce symptoms of knee osteoarthritis. A previous study has shown that compensating for the hip flexion/extension moment could reduce the KCF peak occurring during early stance (KCFp1). Therefore, this study aimed to identify if monoarticular hip muscle could allow this compensation while considering different walking strategies. Gait trials from 24 healthy participants were used to make musculoskeletal models, and five load-cases were examined: (I) Normal, (II) with an applied external moment compensating for 100% of the hip flexion/extension moment, and (III-V) three conditions with isolated/combined 30% increase of peak isometric strength of gluteus medius and maximus. Knee contact forces, hip muscle forces, and joint moments were computed. A cluster analysis of the Normal condition was performed with hip and knee flexion/extension moment during KCFp1 as input to examine the influence of different walking strategies. The cluster analysis revealed two groups having significantly different hip and knee moments in early-stance (p < 0.01). The reduction in KCFp1 from the Normal condition, although present in both groups, was greater for the group with the highest hip and lowest knee flexion/extension moments for all conditions tested (II: -21.82 ± 8.71% versus -6.03 ± 6.68%, III: -3.21 ± 1.09% versus -1.59 ± 0.96%, IV: -3.00 ± 0.89% versus -1.76 ± 1.04%, V: -6.12 ± 1.69 versus -3.09 ± 1.95%). This reduction in KCFp1 occurred through a shift in force developed by the hamstrings during walking (biarticular) to the gluteus medius and maximus (monoarticular), whose isometric strength was increased. The differences between the groups suggest that this reduction depends on the walking strategy.

Comparison of a Scaled Cadaver-Based Musculoskeletal Model With a Clinical Upper Extremity Model.

Reliably and accurately estimating joint/segmental kinematics from optical motion capture data has remained challenging. Studies objectively characterizing human movement patterns have typically involved inverse kinematics and inverse dynamics techniques. Subsequent research has included scaled cadaver-based musculoskeletal (MSK) modeling for noninvasively estimating joint and muscle loads. As one of the ways to enhance confidence in the validity of MSK model predictions, the kinematics from the preceding step that drives such a model needs to be checked for agreement or compared with established/widely used models. This study rigorously compares the upper extremity (UE) joint kinematics calculated by the Dutch Shoulder Model implemented in the AnyBody Managed Model Repository (involving multibody kinematics optimization (MKO)) with those estimated by the Vicon Plug-in Gait model (involving single-body kinematics optimization (SKO)). Ten subjects performed three trials of (different types of) reaching tasks in a three-dimensional marker-based optical motion capture laboratory setting. Joint angles, processed marker trajectories, and reconstruction residuals corresponding to both models were compared. Scatter plots and Bland-Altman plots were used to assess the agreement between the two model outputs. Results showed the largest differences between the two models for shoulder, followed by elbow and wrist, with all root-mean-squared differences less than 10 deg (although this limit might be unacceptable for clinical use). Strong-to-excellent Spearman's rank correlation coefficients were found between the two model outputs. The Bland-Altman plots showed a good agreement between most of the outputs. In conclusion, results indicate that these two models with different kinematic algorithms broadly agree with each other, albeit with few key differences.

Medial congruent polyethylene design show different tibiofemoral kinematics and enhanced congruency compared to a standard symmetrical cruciate retaining design for total knee arthroplasty-an in vivo randomized controlled study of gait using dynamic radiostereometry.

PURPOSE: New total knee arthroplasty implant designs attempt to normalize kinematics patterns that may improve functional performance and patient satisfaction. It was hypothesized that a more medial congruent (MC) anatomic bearing design (1) influences the tibiofemoral kinematics and (2) enhances articular congruency compared to a standard symmetrical cruciate retaining (CR) bearing design. METHODS: In this double-blinded randomized study, 66 patients with knee osteoarthritis were randomly included in two groups: MC (n = 31) and CR (n = 33). Clinical characteristics such as knee ligament lesions and knee osteoarthritis scores were graded on preoperative magnetic resonance imaging and radiography. At the 1-year follow-up, dynamic radiostereometric analysis was used to assess tibiofemoral joint kinematics and articulation congruency. Patient-reported outcome measures, Oxford Knee Score, the Forgotten Joint Score, and the Knee Osteoarthritis Outcome Score, were assessed preoperatively and at the 1-year follow-up. RESULTS: Compared to the CR bearing, the MC bearing displayed an offset with approximately 3 mm greater anterior tibial drawer (p < 0.001) during the entire motion, and up to approximately 3.5 degrees more tibial external rotation (p = 0.004) from mid-swing to the end of the gait cycle at the 1-year follow-up. Furthermore, the congruency area in the joint articulation was larger during approximately 80% of the gait cycle for the MC bearing compared to the CR. The patient-reported outcome measures improved (p < 0.001), but there were no differences between groups. In addition, there were no differences in clinical characteristics and there were no knee revisions or recognized deep infections during follow-up. CONCLUSION: The study demonstrates that the MC-bearing design changes tibiofemoral kinematics and increases the area of congruency towards more native knee kinematics than the CR bearing. In perspective this may contribute to a more stabilized knee motion, restoring the patient's confidence in knee function during daily activities.