The independent and combined effects of smoking and chronic obstructive pulmonary disease on body mass index trajectories

Low body mass index (BMI) is a common feature of severe chronic obstructive pulmonary disease (COPD) but in the general population, cigarette smoking is also associated with low body weight. Many people with COPD remain smokers after diagnosis, and it is unclear whether low BMI is because of the disease itself or its most common risk factor. We aim to assess the independent and combined effects of smoking and COPD on BMI trajectories. 27,651 patients without COPD and 25,990 with COPD from The Health Improvement Network (2005-2019) were grouped into: never-smokers, former smokers, sustained quitters, intermittent smokers, and continuous smokers (ten total COPD-smoking status groups). BMI trajectories over 10-year time horizon were modeled by these status groups using multivariable mixed-effect models adjusted for age (in continuous years), sex, Townsend score (a measure of material deprivation), alcohol consumption (yes/no), exacerbation history (yes/no, only for COPD patients) and any history of asthma, cancer, chronic kidney disease, diabetes, or cardiovascular disease (yes/no). Individuals with COPD who smoked at baseline (intermittent, sustained quitter, or continuous smokers) had a lower initial BMI (27.1 kg/m² [26.9-27.3]; 26.6 [26.4-26.9]; 26.2 [26.0-26.4], respectively) than non-COPD controls in the same smoking categories (28.0 [26.6-28.2]; 27.6 [27.2-27.9]; 26.7 [26.4-26.9]). Current smokers had lower initial BMIs than never and former smokers, regardless of COPD status. In individuals with COPD, compared to former smokers, continuous smokers lost weight faster (-0.071 kg/m²/year [-0.097 to -0.045]; p &lt; 0.001), while quitters gained weight (0.266 [0.233 to 0.298]; p &lt; 0.001). Non-COPD controls showed similar but less pronounced patterns when continuous smokers and quitters (-0.059 [-0.090 to -0.028] and 0.213 [0.173 to 0.254], respectively; both p &lt; 0.001) were compared to former smokers. Those with a baseline BMI of &lt; 30 also showed a decrease in longitudinal BMI, especially among COPD patients. COPD patients had lower baseline BMI than controls, but BMI trajectories were similar between groups, with continuous smokers losing weight faster and quitters gaining weight. These findings suggest that smoking behaviour significantly influences weight loss in COPD, emphasizing its importance in clinical evaluations and nutritional support consultations.</p

Surgical Management of Focal Chondral Defects of the Talus. A Bayesian Network Meta-analysis

Background: No consensus has been reached regarding the optimal surgical treatment for focal chondral defects of the talus. Purpose: A Bayesian network meta-analysis was conducted to compare the clinical scores and complications of mosaicplasty, osteochondral auto- and allograft transplant, microfracture, matrix-assisted autologous chondrocyte transplant, and autologous matrix-induced chondrogenesis (AMIC) for chondral defects of the talus at midterm follow-up. Study design: Bayesian network meta-analysis; Level of evidence, 4. Methods: This Bayesian network meta-analysis followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions. PubMed, Embase, Google Scholar, and Scopus databases were accessed in February 2021. All clinical trials comparing 2 or more surgical interventions for the management of chondral defects of the talus were accessed. The outcomes of interest were visual analog scale (VAS) score, American Orthopaedic Foot and Ankle Society (AOFAS) score, rate of failure, and rate of revision surgery. The network meta-analysis were performed through the routine for Bayesian hierarchical random-effects model analysis. The log odds ratio (LOR) effect measure was used for dichotomous variables, and the standardized mean difference (SMD) was used for continuous variables. Results: Data from 13 articles (521 procedures) were retrieved. The median length of the follow-up was 47.8 months (range, 31.7-66.8 months). Analysis of variance revealed no difference between the treatment groups at baseline in terms of age, sex, body mass index, AOFAS score, VAS score, and mean number of defects. AMIC demonstrated the greatest AOFAS score (SMD, 11.27) and lowest VAS score (SMD, -2.26) as well as the lowest rates of failure (LOR, 0.94) and revision (LOR, 0.94). The test for overall inconsistency was not significant. Conclusion: At approximately 4 years of follow-up, the AMIC procedure for management of focal chondral defects of the talus produced the best outcome

Identification of single-cell blasts in pediatric acute myeloid leukemia using an autoencoder

Pediatric acute myeloid leukemia (AML) is an aggressive blood cancer with a poor prognosis and high relapse rate. Current challenges in the identification of immunotherapy targets arise from patient-specific blast immunophenotypes and their change during disease progression. To overcome this, we present a new computational research tool to rapidly identify malignant cells. We generated single-cell flow cytometry profiles of 21 pediatric AML patients with matched samples at diagnosis, remission, and relapse. We coupled a classifier to an autoencoder for anomaly detection and classified malignant blasts with 90% accuracy. Moreover, our method assigns a developmental stage to blasts at the single-cell level, improving current classification approaches based on differentiation of the dominant phenotype. We observed major immunophenotype and developmental stage alterations between diagnosis and relapse. Patients with KMT2A rearrangement had more profound changes in their blast immunophenotypes at relapse compared to patients with other molecular features. Our method provides new insights into the immunophenotypic composition of AML blasts in an unbiased fashion and can help to define immunotherapy targets that might improve personalized AML treatment

Rethinking ‘recovery’: A comparative qualitative analysis of experiences of Intensive Care with COVID and Long Covid in the United Kingdom

Introduction Interpretations of ‘recovery’ from illness are complex and influenced by many factors, not least patient expectations and experiences. This paper examines meanings of ‘recovery’, and how it is strived towards, drawing on the example of COVID-19 infection. Methods Drawing on qualitative interviews (n = 93) conducted in the UK between February 2021 and July 2022, we compare adults' accounts of being admitted to an Intensive Care Unit (ICU) with COVID-19 to accounts of being ill with Long COVID, defined as ongoing symptoms for at least 12 weeks postinfection. We conducted a multi-stage comparative analysis using Nvivo to organise and code the data. Results We identified similarities and differences in participants' descriptions of their ‘worlds of illness’. For both groups, perceptions of recovery were shaped by the novel, unknown nature of COVID-19. Participants questioned the achievability of full restoration of prior states of health, highlighted the heterogeneity of ‘recovery trajectories’ and described the hard physical and emotional work of adjusting to changed selves. Themes that revealed differences in ‘worlds of illness’ described included the different baselines, waymarkers, and pathways of illness experiences. Differences in other people's responses to their illness were also evident. For ICU participants, hospitalisation, and especially ICU admission, conferred legitimate patient status and authenticity to their symptoms. Family, friends and healthcare professionals acknowledged their illness, celebrated their survival, and granted them latitude to recover. For Long Covid participants, their patient status often lacked comparable authenticity in others' eyes. They reported encountering a lack of recognition and understanding of their ongoing need to recover

Cell-to-cell and type-to-type heterogeneity of signaling networks: insights from the crowd.

Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi-signaling networks across cells and cell types, with important implications to understand and treat diseases such as cancer. These technologies are, however, limited to proteins for which antibodies are available and are fairly costly, making predictions of new markers and of existing markers under new conditions a valuable alternative. To assess our capacity to make such predictions and boost further methodological development, we organized the Single Cell Signaling in Breast Cancer DREAM challenge. We used a mass cytometry dataset, covering 36 markers in over 4,000 conditions totaling 80 million single cells across 67 breast cancer cell lines. Through four increasingly difficult subchallenges, the participants predicted missing markers, new conditions, and the time-course response of single cells to stimuli in the presence and absence of kinase inhibitors. The challenge results show that despite the stochastic nature of signal transduction in single cells, the signaling events are tightly controlled and machine learning methods can accurately predict new experimental data

Cell‐to‐cell and type‐to‐type heterogeneity of signaling networks: insights from the crowd

Recent technological developments allow us to measure the status of dozens of proteins in individual cells. This opens the way to understand the heterogeneity of complex multi-signaling networks across cells and cell types, with important implications to understand and treat diseases such as cancer. These technologies are, however, limited to proteins for which antibodies are available and are fairly costly, making predictions of new markers and of existing markers under new conditions a valuable alternative. To assess our capacity to make such predictions and boost further methodological development, we organized the Single Cell Signaling in Breast Cancer DREAM challenge. We used a mass cytometry dataset, covering 36 markers in over 4,000 conditions totaling 80 million single cells across 67 breast cancer cell lines. Through four increasingly difficult subchallenges, the participants predicted missing markers, new conditions, and the time-course response of single cells to stimuli in the presence and absence of kinase inhibitors. The challenge results show that despite the stochastic nature of signal transduction in single cells, the signaling events are tightly controlled and machine learning methods can accurately predict new experimental data

The role of the paratrigeminal nucleus in vagal afferent evoked respiratory reflexes: a neuroanatomical and functional study in guinea pigs

The respiratory tree receives sensory innervation from the jugular and nodose vagal sensory ganglia. Neurons of these ganglia are derived from embryologically distinct origins and as such demonstrate differing molecular, neurochemical and physiological phenotypes. Furthermore, whereas nodose afferent neurons project to the nucleus of the solitary tract (nTS), recent neuroanatomical studies in rats suggest that jugular neurons have their central terminations in the paratrigeminal nucleus (Pa5). In the present study we confirm that guinea pigs demonstrate a comparable distinction between the brainstem terminations of nodose and jugular ganglia afferents. Thus, microinjection of fluorescently conjugated cholera toxin B (CT-B) neural tracers into the caudal nTS and Pa5 resulted in highly specific retrograde labelling of neurons in the nodose and jugular ganglia, respectively. Whereas nodose neurons more often expressed 160KD neurofilament proteins and the alpha3 subunit of Na+/K+ ATPase, significantly more jugular neurons expressed the neuropeptides substance P (SP) and, especially, Calcitonin Gene-Related Peptide (CGRP). Indeed, terminal fibers in the Pa5 compared to the nTS were characterized by their significantly greater expression of CGRP, further supporting the notion that jugular afferents project to trigeminal-related brainstem regions. Electrical stimulation of the guinea pig larynx following selective surgical denervation of the nodose afferent innervation to the larynx (leaving intact the jugular innervation) resulted in stimulus dependent respiratory slowing and eventual apnea. This jugular ganglia neuron mediated response was unaffected by bilateral microinjections of the GABAA agonist muscimol into the nTS, but was abolished by muscimol injected into the Pa5. Taken together these data confirm that jugular and nodose vagal ganglia afferent neurons innervate distinct central circuits and support the notion that multiple peripheral and central pathways mediate sensory responses associated with airway irritations

Reliability of the MOCART score: a systematic review

Abstract Background The present systematic review analysed the available literature to assess reliability of the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score in the evaluation of knee and ankle osteochondral lesions. Methods All the studies using the MOCART score for knee and/or talus chondral defects were accessed in March 2021. A multivariate analysis was performed to assess associations between the MOCART score at last follow-up and data of patients at baseline, clinical scores and complications. A multiple linear model regression analysis was used. Results The MOCART score evidenced no association with patient age (P = 0.6), sex (P = 0.1), body mass index (P = 0.06), defect size (P = 0.9), prior length of symptoms (P = 0.9) or visual analogue scale (P = 0.07). For chondral defects of the knee, no statistically significant association was found between the MOCART score and the International Knee Documentation Committee (P = 0.9) and with the Lysholm Knee Scoring Scales (P = 0.2), Tegner Activity Scale (P = 0.2), visual analogue scale P = 0.07), rate of failure (P = 0.2) and revision (P = 0.9). For chondral defect of the talus, no statistically significant associations were found between the MOCART score and the American Orthopedic Foot and Ankle Score (P = 0.3), Tegner Activity Scale (P = 0.4), visual analogue scale (P = 0.1), rate of failure (P = 0.1) and revision (P = 0.7). Conclusion The MOCART score demonstrated no association with patient characteristics and with the surgical outcome in patients who underwent surgical management for knee and talus chondral defects. Level of evidence Level IV. </jats:sec

Multiple neural circuits mediating airway sensations: recent advances in the neurobiology of the urge-to-cough

The respiratory system is densely innervated by sensory neurons arising from the jugular (superior) and nodose (inferior) vagal ganglia. However, a distinction exists between jugular and nodose neurons as these ganglia developmentally originate from the neural crest and the epibranchial placodes, respectively. This different embryological origin underpins an important source of heterogeneity in vagal afferent biology, and may extend to include fundamentally different central neural circuits that are in receipt of jugular versus nodose afferent inputs. Indeed, recent studies using viral tract tracing and human brain imaging support the notion that airway sensors contribute inputs to multiple central circuits. Understanding the neural pathways arising from the airways and lungs may provide novel insights into aberrant sensations, such as the urge-to-cough, characteristic of respiratory disease