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Cell Reports Jun 2024Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched...
Heterogeneous resistance to immunotherapy remains a major challenge in cancer treatment, often leading to disease progression and death. Using CITE-seq and matched 40-plex PhenoCycler tissue imaging, we performed longitudinal multimodal single-cell analysis of tumors from metastatic melanoma patients with innate resistance, acquired resistance, or response to immunotherapy. We established the multimodal integration toolkit to align transcriptomic features, cellular epitopes, and spatial information to provide deeper insights into the tumors. With longitudinal analysis, we identified an "immune-striving" tumor microenvironment marked by peri-tumor lymphoid aggregates and low infiltration of T cells in the tumor and the emergence of MITFSPARCL1 and CENPF melanoma subclones after therapy. The enrichment of B cell-associated signatures in the molecular composition of lymphoid aggregates was associated with better survival. These findings provide further insights into the establishment of microenvironmental cell interactions and molecular composition of spatial structures that could inform therapeutic intervention.
PubMed: 38944836
DOI: 10.1016/j.celrep.2024.114392 -
Clinical Nutrition ESPEN Jun 2024Accurate diagnosis of sarcopenia requires evaluation of muscle quality, which refers to the amount of fat infiltration in muscle tissue. In this study, we aim to...
Low muscle quality on a procedural computed tomography scan assessed with deep learning as a practical useful predictor of mortality in patients with severe aortic valve stenosis.
BACKGROUND & AIMS
Accurate diagnosis of sarcopenia requires evaluation of muscle quality, which refers to the amount of fat infiltration in muscle tissue. In this study, we aim to investigate whether we can independently predict mortality risk in transcatheter aortic valve implantation (TAVI) patients, using automatic deep learning algorithms to assess muscle quality on procedural computed tomography (CT) scans.
METHODS
This study included 1199 patients with severe aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) between January 2010 and January 2020. A procedural CT scan was performed as part of the preprocedural-TAVI evaluation, and the scans were analyzed using deep-learning-based software to automatically determine skeletal muscle density (SMD) and intermuscular adipose tissue (IMAT). The association of SMD and IMAT with all-cause mortality was analyzed using a Cox regression model, adjusted for other known mortality predictors, including muscle mass.
RESULTS
The mean age of the participants was 80 ± 7 years, 53% were female. The median observation time was 1084 days, and the overall mortality rate was 39%. We found that the lowest tertile of muscle quality, as determined by SMD, was associated with an increased risk of mortality (HR 1.40 [95%CI: 1.15-1.70], p < 0.01). Similarly, low muscle quality as defined by high IMAT in the lowest tertile was also associated with increased mortality risk (HR 1.24 [95%CI: 1.01-1.52], p = 0.04).
CONCLUSIONS
Our findings suggest that deep learning-assessed low muscle quality, as indicated by fat infiltration in muscle tissue, is a practical, useful and independent predictor of mortality after TAVI.
PubMed: 38944828
DOI: 10.1016/j.clnesp.2024.06.013 -
JAMA Health Forum Jun 2024The Centers for Medicare & Medicaid Services' mandatory End-Stage Renal Disease Treatment Choices (ETC) model, launched on January 1, 2021, randomly assigned...
IMPORTANCE
The Centers for Medicare & Medicaid Services' mandatory End-Stage Renal Disease Treatment Choices (ETC) model, launched on January 1, 2021, randomly assigned approximately 30% of US dialysis facilities and managing clinicians to financial incentives to increase the use of home dialysis and kidney transplant.
OBJECTIVE
To assess the ETC's association with use of home dialysis and kidney transplant during the model's first 2 years and examine changes in these outcomes by race, ethnicity, and socioeconomic status.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cross-sectional study used claims and enrollment data for traditional Medicare beneficiaries with kidney failure from 2017 to 2022 linked to same-period transplant data from the United Network for Organ Sharing. The study data span 4 years (2017-2020) before the implementation of the ETC model on January 1, 2021, and 2 years (2021-2022) following the model's implementation.
EXPOSURE
Receiving dialysis treatment in a region randomly assigned to the ETC model.
MAIN OUTCOMES AND MEASURES
Primary outcomes were use of home dialysis and kidney transplant. A difference-in-differences (DiD) approach was used to estimate changes in outcomes among patients treated in regions randomly selected for ETC participation compared with concurrent changes among patients treated in control regions.
RESULTS
The study population included 724 406 persons with kidney failure (mean [IQR] age, 62.2 [53-72] years; 42.5% female). The proportion of patients receiving home dialysis increased from 12.1% to 14.3% in ETC regions and from 12.9% to 15.1% in control regions, yielding an adjusted DiD estimate of -0.2 percentage points (pp; 95% CI, -0.7 to 0.3 pp). Similar analysis for transplant yielded an adjusted DiD estimate of 0.02 pp (95% CI, -0.01 to 0.04 pp). When further stratified by sociodemographic measures, including age, sex, race and ethnicity, dual Medicare and Medicaid enrollment, and poverty quartile, there was not a statistically significant difference in home dialysis use across joint strata of characteristics and ETC participation.
CONCLUSIONS AND RELEVANCE
In this cross-sectional study, the first 2 years of the ETC model were not associated with increased use of home dialysis or kidney transplant, nor changes in racial, ethnic, and socioeconomic disparities in these outcomes.
Topics: Humans; Kidney Transplantation; Female; Male; Cross-Sectional Studies; Hemodialysis, Home; United States; Reimbursement, Incentive; Retrospective Studies; Kidney Failure, Chronic; Aged; Middle Aged; Medicare
PubMed: 38944762
DOI: 10.1001/jamahealthforum.2024.2055 -
BMC Pulmonary Medicine Jun 2024For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve...
BACKGROUND
For patients with congenital heart disease-related pulmonary arterial hypertension (CHD-PAH), cardiopulmonary exercise testing (CPET) can reflect cardiopulmonary reserve function. However, CPET may not be readily accessible for patients with high-risk conditions or limited mobility due to disability. Echocardiography, on the other hand, serves as a widely available diagnostic tool for all CHD-PAH patients. This study was aimed to identify the parameters of echocardiography that could serve as indicators of cardiopulmonary function and exercise capacity.
METHODS
A cohort of 70 patients contributed a total of 110 paired echocardiogram and CPET results to this study, with 1 year interval for repeated examinations. Echocardiography and exercise testing were conducted following standardized procedures, and the data were collected together with clinically relevant indicators for subsequent statistical analysis. Demographic comparisons were performed using t-tests and chi-square tests. Univariate and multivariate analyses were conducted to identify potential predictors of peak oxygen uptake (peak VO) and the carbon dioxide ventilation equivalent slope (VE/VCO slope). Receiver operating characteristic (ROC) analysis was used to assess the performance of the parameters.
RESULTS
The ratio of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) was found to be the only independent indicator significantly associated with both peak VO and VE/VCO slope (both p < 0.05). Additionally, left ventricular ejection fraction (LVEF) and right ventricular fractional area change (FAC) were independently correlated with the VE/VCO slope (both p < 0.05). TAPSE/PASP showed the highest area under the ROC curve (AUC) for predicting both a peak VO ≤ 15 mL/kg/min and a VE/VCO slope ≥ 36 (AUC = 0.91, AUC = 0.90, respectively). The sensitivity and specificity of TAPSE/PASP at the optimal threshold exceeded 0.85 for both parameters.
CONCLUSIONS
TAPSE/PASP may be a feasible echocardiographic indicator for evaluating exercise tolerance.
Topics: Humans; Female; Male; Exercise Test; Heart Defects, Congenital; Echocardiography; Adult; ROC Curve; Exercise Tolerance; Pulmonary Arterial Hypertension; Oxygen Consumption; Middle Aged; Young Adult; Hypertension, Pulmonary; Pulmonary Artery
PubMed: 38944669
DOI: 10.1186/s12890-024-03113-7 -
Journal of Medical Case Reports Jun 2024Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest...
BACKGROUND
Choriocarcinoma is a highly malignant pregnancy-related trophoblastic neoplasm, characterized by early metastasis to the lungs. Therefore, patients may manifest nongynecological symptoms owing to distant metastases. The incidence of choriocarcinoma after a term pregnancy is really rare (1/160,000 pregnancies).
CASE PRESENTATION
We report a case of a 20-year-old Iranian woman, gravida 2 para 1 live 1 abortion 1, who was referred to our gynecology department with sudden onset dyspnea and pain in the left hemithorax the day after her labor. The index pregnancy was without any complications. After the initial workup, the elevation of β-human chorionic gonadotropin (HCG) levels (> 1,000,000) along with the identification of clinical (vaginal lesions) and radiological evidence of distant metastases (bilateral pulmonary nodes) directed us toward pulmonary metastatic choriocarcinoma diagnosis. After the oncology consult, the etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine chemotherapy regimen was started for the patient. She responded well to the treatment and is currently continuing her chemotherapy process.
CONCLUSION
The prognosis of choriocarcinoma is very good if the treatment is started on time. We suggest that clinicians should consider gestational trophoblastic neoplasia in their differential diagnosis of the post-natal period complications, especially after a term and nonmolar pregnancy.
Topics: Humans; Female; Pregnancy; Lung Neoplasms; Choriocarcinoma; Uterine Neoplasms; Young Adult; Antineoplastic Combined Chemotherapy Protocols; Methotrexate; Vincristine; Dactinomycin; Etoposide; Chorionic Gonadotropin, beta Subunit, Human; Cyclophosphamide; Dyspnea; Pregnancy Complications, Neoplastic
PubMed: 38944668
DOI: 10.1186/s13256-024-04615-y -
BMC Infectious Diseases Jun 2024An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF).... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An improper host immune response to Mycoplasma pneumoniae generates excessive inflammation, which leads to the impairment of pulmonary ventilation function (PVF). Azithromycin plus inhaled terbutaline has been used in the treatment of Mycoplasma pneumoniae pneumonia (MPP) in children with impaired pulmonary function, but previous randomized controlled trials (RCTs) showed inconsistent efficacy and safety. This study is aimed to firstly provide a systematic review of the combined therapy.
METHODS
This study was registered at the International Prospective Register of Systematic Reviews (PROSPERO CRD42023452139). A PRISMA-compliant systematic review and meta-analysis was performed. Six English and four Chinese databases were comprehensively searched up to June, 2023. RCTs of azithromycin sequential therapy plus inhaled terbutaline were selected. The revised Cochrane risk of bias tool for randomized trials (RoB2) was used to evaluate the methodological quality of all studies, and meta-analysis was performed using Stata 15.0 with planned subgroup and sensitivity analyses. Publication bias was evaluated by a funnel plot and the Harbord' test. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation recommendations.
RESULTS
A total of 1,938 pediatric patients from 20 RCTs were eventually included. The results of meta-analysis showed that combined therapy was able to significantly increase total effectiveness rate (RR = 1.20, 95%CI 1.15 to 1.25), forced expiratory volume in one second (SMD = 1.14, 95%CIs, 0.98 to 1.29), the ratio of forced expiratory volume in one second/forced vital capacity (SMD = 2.16, 95%CIs, 1.46 to 2.86), peak expiratory flow (SMD = 1.17, 95%CIs, 0.91 to 1.43). The combined therapy was associated with a 23% increased risk of adverse reactions compared to azithromycin therapy alone, but no significant differences were found. Harbord regression showed no publication bias (P = 0.148). The overall quality of the evidence ranged from moderate to very low.
CONCLUSIONS
This first systematic review and meta-analysis suggested that azithromycin sequential therapy plus inhaled terbutaline was safe and beneficial for children with MPP. In addition, the combined therapy represented significant improvement of PVF. Due to lack of high-quality evidence, our results should be confirmed by adequately powered RCTs in the future.
Topics: Humans; Azithromycin; Terbutaline; Pneumonia, Mycoplasma; Child; Anti-Bacterial Agents; Mycoplasma pneumoniae; Drug Therapy, Combination; Administration, Inhalation; Treatment Outcome; Randomized Controlled Trials as Topic; Child, Preschool
PubMed: 38944667
DOI: 10.1186/s12879-024-09564-x -
Nature Communications Jun 2024Real-time genomics through nanopore sequencing holds the promise of fast antibiotic resistance prediction directly in the clinical setting. However, concerns about the...
Real-time genomics through nanopore sequencing holds the promise of fast antibiotic resistance prediction directly in the clinical setting. However, concerns about the accuracy of genomics-based resistance predictions persist, particularly when compared to traditional, clinically established diagnostic methods. Here, we leverage the case of a multi-drug resistant Klebsiella pneumoniae infection to demonstrate how real-time genomics can enhance the accuracy of antibiotic resistance profiling in complex infection scenarios. Our results show that unlike established diagnostics, nanopore sequencing data analysis can accurately detect low-abundance plasmid-mediated resistance, which often remains undetected by conventional methods. This capability has direct implications for clinical practice, where such "hidden" resistance profiles can critically influence treatment decisions. Consequently, the rapid, in situ application of real-time genomics holds significant promise for improving clinical decision-making and patient outcomes.
Topics: Klebsiella pneumoniae; Genomics; Humans; Anti-Bacterial Agents; Klebsiella Infections; Drug Resistance, Multiple, Bacterial; Plasmids; Nanopore Sequencing; Genome, Bacterial; Microbial Sensitivity Tests
PubMed: 38944650
DOI: 10.1038/s41467-024-49851-4 -
Journal of Cardiovascular Computed... Jun 2024Coronary artery lumen volume (V) to myocardial mass (M) ratio (V/M) can show the mismatch between epicardial coronary arteries and the underlying myocardium.
BACKGROUND
Coronary artery lumen volume (V) to myocardial mass (M) ratio (V/M) can show the mismatch between epicardial coronary arteries and the underlying myocardium.
METHODS
The V, M and V/M were obtained from the coronary computed tomography angiography (CCTA) of patients in the FAST-TRACK CABG study, the first-in-human trial of coronary artery bypass grafting (CABG) guided solely by CCTA and fractional flow reserve derived from CCTA (FFR) in patients with complex coronary artery disease (CAD). The correlations between V/M ratios and baseline characteristics were determined and compared with those from the ADVANCE registry, an unselected cohort of historical controls with chronic CAD.
RESULTS
The V/M ratio was obtained in 106 of the 114 pre-CABG CCTAs. Mean age was 65.6 years and 87% of them were male. The anatomical SYNTAX score from CCTA was significantly higher than the functional SYNTAX score derived using FFR [43.1 (15.2) vs 41.1 (16.5), p < 0.001]. Mean V, M, and V/M were 2204 mm, 137 g, and 16.5 mm/g, respectively. There were weak negative correlations between V and anatomical and functional SYNTAX scores (Pearson's r = -0.26 and -0.34). V and V/M had a strong correlation (r = 0.82). The V/M ratio in the current study was significantly lower than that in the ADVANCE registry (median 16.1 vs. 24.8 [1st quartile 20.1]).
CONCLUSION
Systematically smaller V/M ratios were found in this population with severe CAD requiring CABG compared to an unselected cohort with chronic CAD. The V/M ratio could provide additional non-invasive assessment of CAD especially when combined with FFR.
PubMed: 38944640
DOI: 10.1016/j.jcct.2024.06.010 -
Neurotherapeutics : the Journal of the... Jun 2024Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique for modulating cortical activities and improving neural plasticity....
Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique for modulating cortical activities and improving neural plasticity. Several studies investigated the effects of rTMS, etc., but the results are inconsistent. This study was designed to examine whether rTMS applied on the left dorsolateral prefrontal cortex (l-DLPFC) showed an effect on improving cognitive deficits in SZ and whether the early efficacy could predict efficacy at subsequent follow-ups. Cognitive ability was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) scale at baseline, weeks 2, 6, and 24. We found a significant interaction between time (weeks 0, 2, 6, and 24) and intervention on immediate memory and RBANS total scores (p = 0.02 and p = 0.04), indicating that both 10-Hz and 20-Hz rTMS stimulations had a delayed beneficial effect on immediate memory in SZ. Moreover, we found that 20-Hz rTMS stimulation, but not 10-Hz rTMS improved immediate memory at week 6 compared to the sham group (p = 0.029). More importantly, improvements in immediate memory at week 2 were positively correlated with improvements at week 24 (β = 0.461, t = 3.322, p = 0.002). Our study suggests that active rTMS was beneficial for cognitive deficits in patients with SZ. Furthermore, efficacy at week 2 could predict the subsequent efficacy at 24-week follow-up.
PubMed: 38944636
DOI: 10.1016/j.neurot.2024.e00392 -
Medicina Clinica Jun 2024After the COVID-19 pandemic, the omicron variant of the SARS-CoV-2 virus became the dominant lineage in Spain in 2022. Although it possesses a milder pathogenicity than... (Review)
Review
After the COVID-19 pandemic, the omicron variant of the SARS-CoV-2 virus became the dominant lineage in Spain in 2022. Although it possesses a milder pathogenicity than previous variants, it still poses a high risk of causing severe COVID-19 for immunocompromised populations. A systematic review was conducted to assess the burden of COVID-19 in Spain among immunocompromised patients during the omicron predominance (1/04/2022-1/04/2023), using PubMed, Cochrane Library, and EPICOVIDEHA between May and July 2023. The search retrieved 217 articles, of which a total of 5 were included. Upon analysis, it was observed that immunocompromised patients during the omicron lineage predominance continue to exhibit higher rates of hospitalizations, ICU admissions, and mortality compared to the general population affected by COVID-19. Although the pandemic has ended, the risk persists for immunocompromised individuals.
PubMed: 38944615
DOI: 10.1016/j.medcli.2024.04.009