Communications Medicine

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EISSN : 2730-664X
Published by: Springer Nature (10.1038)
Total articles ≅ 112
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Michael Asger Andersen, Mia Klinten Grand, Christian Brieghel, Volkert Siersma, Christen Lykkegaard Andersen,
Published: 12 May 2022
Communications Medicine, Volume 2, pp 1-8; https://doi.org/10.1038/s43856-022-00117-4

Abstract:
Background: The dynamics of pre-diagnostic lymphocytosis in patients with ensuing chronic lymphocytic leukemia (CLL) need to be explored as a better understanding of disease progression may improve treatment options and even lead to disease avoidance approaches. Our aim was to investigate the development of lymphocytosis prior to diagnosis in a population-based cohort of patients with CLL and to assess the prognostic information in these pre-diagnostic measurements. Methods: All patients diagnosed with CLL in the Greater Copenhagen area between 2008 and 2016 were included in the study. Pre-diagnostic blood test results were obtained from the Copenhagen Primary Care Laboratory Database encompassing all blood tests requested by Copenhagen general practitioners. Using pre-diagnostic measurements, we developed a model to assess the prognosis following diagnosis. Our model accounts for known prognostic factors and corresponds to lymphocyte dynamics after diagnosis. Results: We explore trajectories of lymphocytosis, associated with known recurrent mutations. We show that the pre-diagnostic trajectories are an independent predictor of time to treatment. The implementation of pre-diagnostic lymphocytosis slope groups improved the model predictions (compared to CLL-IPI alone) for treatment throughout the period. The model can manage the heterogeneous data that are to be expected from the real-world setting and adds further prognostic information. Conclusions: Our findings further knowledge of the development of CLL and may eventually make prophylactic measures possible.
Li Wen, Zhiwen Ou, Wenzhou Duan, Weijie Zhu, Xiongzhi Xiao, Ying Zhang, Huanquan Luo, , Wanmin Lian
Published: 12 May 2022
Communications Medicine, Volume 2, pp 1-4; https://doi.org/10.1038/s43856-022-00118-3

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, Aniko Szabo, Igli Arapi, Ruizhe Wu, Amanda Emmrich, Edward Hackett, Garrett Sauber, Sharon Yim, Bryon Johnson, , et al.
Published: 12 May 2022
Communications Medicine, Volume 2, pp 1-10; https://doi.org/10.1038/s43856-022-00116-5

Abstract:
Background: With the rising number of chimeric antigen receptor (CAR) T cell treated patients, it is increasingly important to understand the treatment’s impact on patient-reported outcomes (PROs) and, ideally, identify biomarkers of central nervous system (CNS) adverse effects. Methods: The purpose of this exploratory study was to assess short-term PROs and serum kynurenine metabolites for associated neurotoxicity among patients treated in an anti-CD20, anti-CD19 (LV20.19) CAR T cell phase I clinical trial (NCT03019055). Fifteen CAR T treated patients from the parent trial provided serum samples and self-report surveys 15 days before and 14, 28, and 90 days after treatment. Results: Blood kynurenine concentrations increased over time in patients with evidence of neurotoxicity (p = 0.004) and were increased in self-reported depression (r = 0.52, p = 0.002). Depression improved after CAR T infusion (p = 0.035). Elevated 3-hydroxyanthranilic acid (3HAA) concentrations prior to cell infusion were also predictive of neurotoxicity onset (p = 0.031), suggesting it is a biomarker of neurotoxicity following CAR T cell therapy. Conclusions: Elevated levels of kynurenine pathway metabolites among CAR T cell recipients are associated with depressed mood and neurotoxicity. Findings from this exploratory study are preliminary and warrant validation in a larger cohort.
Annika Rähni, Mariliis Jaago, Helle Sadam, Nadežda Pupina, Arno Pihlak, Jürgen Tuvikene, Margus Annuk, Andrus Mägi, , Amir M. Ghaemmaghami, et al.
Published: 11 May 2022
Communications Medicine, Volume 2, pp 1-11; https://doi.org/10.1038/s43856-022-00114-7

Abstract:
Background: Immunotherapies, including cancer vaccines and immune checkpoint inhibitors have transformed the management of many cancers. However, a large number of patients show resistance to these immunotherapies and current research has provided limited findings for predicting response to precision immunotherapy treatments. Methods: Here, we applied the next generation phage display mimotope variation analysis (MVA) to profile antibody response and dissect the role of humoral immunity in targeted cancer therapies, namely anti-tumor dendritic cell vaccine (MelCancerVac®) and immunotherapy with anti-PD-1 monoclonal antibodies (pembrolizumab). Results: Analysis of the antibody immune response led to the characterization of epitopes that were linked to melanoma-associated and cancer-testis antigens (CTA) whose antibody response was induced upon MelCancerVac® treatments of lung cancer. Several of these epitopes aligned to antigens with strong immune response in patients with unresectable metastatic melanoma receiving anti-PD-1 therapy. Conclusions: This study provides insights into the differences and similarities in tumor-specific immunogenicity related to targeted immune treatments. The antibody epitopes as biomarkers reflect melanoma-associated features of immune response, and also provide insights into the molecular pathways contributing to the pathogenesis of cancer. Concluding, antibody epitope response can be useful in predicting anti-cancer immunity elicited by immunotherapy.
Published: 25 April 2022
Communications Medicine, Volume 2, pp 1-18; https://doi.org/10.1038/s43856-022-00110-x

Abstract:
Background: Adaptive therapy aims to tackle cancer drug resistance by leveraging resource competition between drug-sensitive and resistant cells. Here, we present a theoretical study of intra-tumoral competition during adaptive therapy, to investigate under which circumstances it will be superior to aggressive treatment. Methods: We develop and analyse a simple, 2-D, on-lattice, agent-based tumour model in which cells are classified as fully drug-sensitive or resistant. Subsequently, we compare this model to its corresponding non-spatial ordinary differential equation model, and fit it to longitudinal prostate-specific antigen data from 65 prostate cancer patients undergoing intermittent androgen deprivation therapy following biochemical recurrence. Results: Leveraging the individual-based nature of our model, we explicitly demonstrate competitive suppression of resistance during adaptive therapy, and examine how different factors, such as the initial resistance fraction or resistance costs, alter competition. This not only corroborates our theoretical understanding of adaptive therapy, but also reveals that competition of resistant cells with each other may play a more important role in adaptive therapy in solid tumours than was previously thought. To conclude, we present two case studies, which demonstrate the implications of our work for: (i) mathematical modelling of adaptive therapy, and (ii) the intra-tumoral dynamics in prostate cancer patients during intermittent androgen deprivation treatment, a precursor of adaptive therapy. Conclusion: Our work shows that the tumour’s spatial architecture is an important factor in adaptive therapy and provides insights into how adaptive therapy leverages both inter- and intra-specific competition to control resistance.
Rohollah Moosavi Tayebi, Youqing Mu, Taher Dehkharghanian, Catherine Ross, Monalisa Sur, Ronan Foley, Hamid R. Tizhoosh, Clinton J. V. Campbell
Published: 20 April 2022
Communications Medicine, Volume 2, pp 1-14; https://doi.org/10.1038/s43856-022-00107-6

Abstract:
Background: Bone marrow cytology is required to make a hematological diagnosis, influencing critical clinical decision points in hematology. However, bone marrow cytology is tedious, limited to experienced reference centers and associated with inter-observer variability. This may lead to a delayed or incorrect diagnosis, leaving an unmet need for innovative supporting technologies. Methods: We develop an end-to-end deep learning-based system for automated bone marrow cytology. Starting with a bone marrow aspirate digital whole slide image, our system rapidly and automatically detects suitable regions for cytology, and subsequently identifies and classifies all bone marrow cells in each region. This collective cytomorphological information is captured in a representation called Histogram of Cell Types (HCT) quantifying bone marrow cell class probability distribution and acting as a cytological patient fingerprint. Results: Our system achieves high accuracy in region detection (0.97 accuracy and 0.99 ROC AUC), and cell detection and cell classification (0.75 mean average precision, 0.78 average F1-score, Log-average miss rate of 0.31). Conclusions: HCT has potential to eventually support more efficient and accurate diagnosis in hematology, supporting AI-enabled computational pathology.
Qile He, Hao-Ting Chang, Chih-Da Wu,
Published: 20 April 2022
Communications Medicine, Volume 2, pp 1-7; https://doi.org/10.1038/s43856-022-00093-9

Abstract:
Background: Frailty is a late-life clinical syndrome resulting from the accumulation of aging-induced decline. Greenspaces measured with normalized difference vegetation index (NDVI) are protective of frailty. However, NDVI is not as informative as structure indices in describing greenspaces’ constitution, shape, and connectivity measured by the largest patch index (LPI), shape index, and cohesion index representing larger, more complex, and more dense greenspaces through higher values. We aim to study the association between greenness structures and frailty in a cohort of Chinese older adults. Methods: We included older adults from 2008–2014 China Longitudinal Healthy Longevity Survey (CLHLS). We used greenspace indices from satellite to quantify structures (area-edge, shape, proximity) at county-level, and calculated frailty index (FI) as an outcome. We did cross-sectional analyses using linear and logistical regression, and longitudinal analyses using the generalized estimating equations (GEE). Results: Among 8776 baseline participants, mean LPI, shape, cohesion, and FI are 7.93, 8.11, 97.6, and 0.17. In cross-sectional analyses, we find negative dose-response relationships for greenspace structures and frailty, especially in females, centenarians, illiterate people, city residents, unmarried people, and individuals with increased frailty. Participants living in the highest quartile of LPI, shape, and cohesion have 32% (95%CI: 21–42%), 35% (95%CI: 24–44%), and 37% (95%CI: 26%–46%) lower odds of frailty than the lowest quartile. However, we do not find a significant association in longitudinal analyses. Conclusions: Higher levels of greenness structures (area-edge, shape, and proximity) might be related to lower frailty, while a clear longitudinal benefit cannot be identified in this analysis.
, Henry E. Symons, Benjamin Moseley, , , , Sadiyah Sheikh, Brian Saccente-Kennedy, Declan Costello, William J. Browne, et al.
Published: 19 April 2022
Communications Medicine, Volume 2, pp 1-9; https://doi.org/10.1038/s43856-022-00103-w

Abstract:
Background: The coronavirus disease-19 (COVID-19) pandemic led to the prohibition of group-based exercise and the cancellation of sporting events. Evaluation of respiratory aerosol emissions is necessary to quantify exercise-related transmission risk and inform mitigation strategies. Methods: Aerosol mass emission rates are calculated from concurrent aerosol and ventilation data, enabling absolute comparison. An aerodynamic particle sizer (0.54–20 μm diameter) samples exhalate from within a cardiopulmonary exercise testing mask, at rest, while speaking and during cycle ergometer-based exercise. Exercise challenge testing is performed to replicate typical gym-based exercise and very vigorous exercise, as determined by a preceding maximally exhaustive exercise test. Results: We present data from 25 healthy participants (13 males, 12 females; 36.4 years). The size of aerosol particles generated at rest and during exercise is similar (unimodal ~0.57–0.71 µm), whereas vocalization also generated aerosol particles of larger size (i.e. was bimodal ~0.69 and ~1.74 µm). The aerosol mass emission rate during speaking (0.092 ng s−1; minute ventilation (VE) 15.1 L min−1) and vigorous exercise (0.207 ng s−1, p = 0.726; VE 62.6 L min−1) is similar, but lower than during very vigorous exercise (0.682 ng s−1, p < 0.001; VE 113.6 L min−1). Conclusions: Vocalisation drives greater aerosol mass emission rates, compared to breathing at rest. Aerosol mass emission rates in exercise rise with intensity. Aerosol mass emission rates during vigorous exercise are no different from speaking at a conversational level. Mitigation strategies for airborne pathogens for non-exercise-based social interactions incorporating vocalisation, may be suitable for the majority of exercise settings. However, the use of facemasks when exercising may be less effective, given the smaller size of particles produced.
Cecília Artico Banho, , , Cíntia Bittar, , Leila Sabrina Ullmann, Beatriz De Carvalho Marques, Gislaine Ceslestino Dutra da Silva, Marília Mazzi Moraes, Maisa Carla Pereira Parra, et al.
Published: 13 April 2022
Communications Medicine, Volume 2, pp 1-11; https://doi.org/10.1038/s43856-022-00108-5

Abstract:
Background: The emergence of the Brazilian variant of concern, Gamma lineage (P.1), impacted the epidemiological profile of COVID-19 cases due to its higher transmissibility rate and immune evasion ability. Methods: We sequenced 305 SARS-CoV-2 whole-genomes and performed phylogenetic analyses to identify introduction events and the circulating lineages. Additionally, we use epidemiological data of COVID-19 cases, severe cases, and deaths to measure the impact of vaccination coverage and mortality risk. Results: Here we show that Gamma introduction in São José do Rio Preto, São Paulo, Brazil, was followed by the displacement of seven circulating SARS-CoV-2 variants and a rapid increase in prevalence two months after its first detection in January 2021. Moreover, Gamma variant is associated with increased mortality risk and severity of COVID-19 cases in younger age groups, which corresponds to the unvaccinated population at the time. Conclusions: Our findings highlight the beneficial effects of vaccination indicated by a pronounced reduction of severe cases and deaths in immunized individuals, reinforcing the need for rapid and massive vaccination.
Jitto Titus, Alan H. B. Wu, Siddharth Biswal, Atandra Burman, Shantanu P. Sengupta, Partho P. Sengupta
Published: 13 April 2022
Communications Medicine, Volume 2, pp 1-8; https://doi.org/10.1038/s43856-022-00104-9

Abstract:
Background: The levels of circulating troponin are principally required in addition to electrocardiograms for the effective diagnosis of acute coronary syndrome. Current standard-of-care troponin assays provide a snapshot or momentary view of the levels due to the requirement of a blood draw. This modality further restricts the number of measurements given the clinical context of the patient. In this communication, we present the development and early validation of non-invasive transdermal monitoring of cardiac troponin-I to detect its elevated state. Methods: Our device relies on infrared spectroscopic detection of troponin-I through the dermis and is tested in stepwise laboratory, benchtop, and clinical studies. Patients were recruited with suspected acute coronary syndrome. Results: We demonstrate a significant correlation (r = 0.7774, P < 0.001, n = 52 biologically independent samples) between optically-derived data and blood-based immunoassay measurements with and an area under receiver operator characteristics of 0.895, sensitivity of 96.3%, and specificity of 60% for predicting a clinically meaningful threshold for defining elevated Troponin I. Conclusion: This preliminary work introduces the potential of a bloodless transdermal measurement of troponin-I based on molecular spectroscopy. Further, potential pitfalls associated with infrared spectroscopic mode of inquiry are outlined including requisite steps needed for improving the precision and overall diagnostic value of the device in future studies.
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