Radiologic screening of high-risk adults reduces lung-cancer-related mortality
; however, a small minority of eligible individuals undergo such screening in the United States
. The availability of ...blood-based tests could increase screening uptake. Here we introduce improvements to cancer personalized profiling by deep sequencing (CAPP-Seq)
, a method for the analysis of circulating tumour DNA (ctDNA), to better facilitate screening applications. We show that, although levels are very low in early-stage lung cancers, ctDNA is present prior to treatment in most patients and its presence is strongly prognostic. We also find that the majority of somatic mutations in the cell-free DNA (cfDNA) of patients with lung cancer and of risk-matched controls reflect clonal haematopoiesis and are non-recurrent. Compared with tumour-derived mutations, clonal haematopoiesis mutations occur on longer cfDNA fragments and lack mutational signatures that are associated with tobacco smoking. Integrating these findings with other molecular features, we develop and prospectively validate a machine-learning method termed 'lung cancer likelihood in plasma' (Lung-CLiP), which can robustly discriminate early-stage lung cancer patients from risk-matched controls. This approach achieves performance similar to that of tumour-informed ctDNA detection and enables tuning of assay specificity in order to facilitate distinct clinical applications. Our findings establish the potential of cfDNA for lung cancer screening and highlight the importance of risk-matching cases and controls in cfDNA-based screening studies.
Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. ...Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.
Display omitted
•Pre-treatment ctDNA features are associated with checkpoint blockade response•Pre-treatment peripheral T cell levels are associated with checkpoint blockade response•Early on-treatment ctDNA dynamics are associated with checkpoint blockade response•Multiparameter noninvasive models can predict checkpoint blockade response in NSCLC
Multiparameter noninvasive models that integrate pre-treatment ctDNA and peripheral immune features, together with early on-treatment ctDNA dynamics, show promise in predicting durable clinical response to immune checkpoint blockade treatment in patients with non-small cell lung cancer.
COVID-19 manifests with respiratory, systemic, and gastrointestinal (GI) symptoms.
SARS-CoV-2 RNA is detected in respiratory and fecal samples, and recent reports demonstrate viral replication in ...both the lung and intestinal tissue.2, 3, 4 Although much is known about early fecal RNA shedding, little is known about long-term shedding, especially in those with mild COVID-19. Furthermore, most reports of fecal RNA shedding do not correlate these findings with GI symptoms.
.
We analyzed the dynamics of fecal RNA shedding up to 10 months after COVID-19 diagnosis in 113 individuals with mild to moderate disease. We also correlated shedding with disease symptoms.
Fecal SARS-CoV-2 RNA is detected in 49.2% 95% confidence interval, 38.2%-60.3% of participants within the first week after diagnosis. Whereas there was no ongoing oropharyngeal SARS-CoV-2 RNA shedding in subjects at 4 months, 12.7% 8.5%-18.4% of participants continued to shed SARS-CoV-2 RNA in the feces at 4 months after diagnosis and 3.8% 2.0%-7.3% shed at 7 months. Finally, we found that GI symptoms (abdominal pain, nausea, vomiting) are associated with fecal shedding of SARS-CoV-2 RNA.
The extended presence of viral RNA in feces, but not in respiratory samples, along with the association of fecal viral RNA shedding with GI symptoms suggest that SARS-CoV-2 infects the GI tract and that this infection can be prolonged in a subset of individuals with COVID-19.
This research was supported by a Stanford ChemH-IMA grant; fellowships from the AACR and NSF; and NIH R01-AI148623, R01-AI143757, and UL1TR003142.
•We assessed spontaneous discourse in Parkinson’s disease (PD) with automatized tools.•Compared to controls, patients used fewer action concepts and more subordinators.•Analysis of grammar choices ...allowed classifying patients and controls above chance.•The incidence of word repetitions predicted the patients’ level of motor impairment.•Naturalistic discourse features may index the integrity of specific neural networks.
To assess the impact of Parkinson’s disease (PD) on spontaneous discourse, we conducted computerized analyses of brief monologues produced by 51 patients and 50 controls. We explored differences in semantic fields (via latent semantic analysis), grammatical choices (using part-of-speech tagging), and word-level repetitions (with graph embedding tools). Although overall output was quantitatively similar between groups, patients relied less heavily on action-related concepts and used more subordinate structures. Also, a classification tool operating on grammatical patterns identified monologues as pertaining to patients or controls with 75% accuracy. Finally, while the incidence of dysfluent word repetitions was similar between groups, it allowed inferring the patients’ level of motor impairment with 77% accuracy. Our results highlight the relevance of studying naturalistic discourse features to tap the integrity of neural (and, particularly, motor) networks, beyond the possibilities of standard token-level instruments.
Despite myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) affecting millions of people worldwide, many clinicians lack the knowledge to appropriately diagnose or manage ME/CFS. ...Unfortunately, clinical guidance has been scarce, obsolete, or potentially harmful. Consequently, up to 91% of patients in the United States remain undiagnosed, and those diagnosed often receive inappropriate treatment. These problems are of increasing importance because after acute COVID-19, a significant percentage of people remain ill for many months with an illness similar to ME/CFS. In 2015, the US National Academy of Medicine published new evidence-based clinical diagnostic criteria that have been adopted by the US Centers for Disease Control and Prevention. Furthermore, the United States and other governments as well as major health care organizations have recently withdrawn graded exercise and cognitive-behavioral therapy as the treatment of choice for patients with ME/CFS. Recently, 21 clinicians specializing in ME/CFS convened to discuss best clinical practices for adults affected by ME/CFS. This article summarizes their top recommendations for generalist and specialist health care providers based on recent scientific progress and decades of clinical experience. There are many steps that clinicians can take to improve the health, function, and quality of life of those with ME/CFS, including those in whom ME/CFS develops after COVID-19. Patients with a lingering illness that follows acute COVID-19 who do not fully meet criteria for ME/CFS may also benefit from these approaches.
Aim
The aim of this study was to describe a case series of patients with primary or secondary antiphospholipid syndrome (APS) treated with direct oral anticoagulants (DOACs).
Patients and methods
...Clinical charts of eight patients with thrombotic primary or secondary APS treated with direct oral anticoagulants (DOACs) between January 2012 and May 2015 were reviewed.
Results
The mean age was 45 ± 14.36 (range 27–69 years). Four patients had secondary APS (50%). All patients were initially treated with warfarin by a mean time of 70.87 ± 57.32 months (range 17–153 months). Changes in anticoagulation were defined by recurring thrombosis in five patients (62.5%) and life-threatening bleeding in the other three cases. Seven patients (87.5%) received rivaroxaban treatment and one patient (12.5%) apixaban. The mean follow-up period with DOACs was 19 ± 10.06 months (range 2–36 months). There was no recurrence of thrombosis by the time of data collection.
Conclusions
Despite not being the standard treatment in APS, we propose DOACs as a rational alternative for the management of patients with this diagnosis. Further interventional clinical studies are necessary for possible standardization of this therapy in APS patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PDF
