Non-invasive detection of lymphoma with circulating tumor DNA features and protein tumor markers

BackgroundAccording to GLOBOCAN 2020, lymphoma ranked as the 9th most common cancer and the 12th leading cause of cancer-related deaths worldwide. Traditional diagnostic methods rely on the invasive excisional lymph node biopsy, which is an invasive approach with some limitations. Most lymphoma patients are diagnosed at an advanced stage since they are asymptomatic at the beginning, which has significantly impacted treatment efficacy and prognosis of the disease.MethodThis study assessed the performance and utility of a newly developed blood-based assay (SeekInCare) for lymphoma early detection. SeekInCare utilized protein tumor markers and a comprehensive set of cancer-associated genomic features, including copy number aberration (CNA), fragment size (FS), end motif, and lymphoma-related virus, which were profiled by shallow WGS of cfDNA.ResultsProtein marker CA125 could be used for lymphoma detection independent of gender, and the sensitivity was 27.8% at specificity of 98.0%. After integrating these multi-dimensional features, 77.8% sensitivity was achieved at specificity of 98.0%, while its NPV and PPV were both more than 92% for lymphoma detection. The sensitivity of early-stage (I-II) lymphoma was up to 51.3% (47.4% and 55.0% for stage I and II respectively). After 2 cycles of treatment, the molecular response of SeekInCare was correlated with the clinical outcome.ConclusionIn summary, a blood-based assay can be an alternative to detect lymphoma with adequate performance. This approach becomes particularly valuable in cases where obtaining tissue biopsy is difficult to obtain or inconclusive

Proposed clinical phases for the improvement of personalized treatment of checkpoint inhibitor–related pneumonitis

BackgroundCheckpoint inhibitor–related pneumonitis (CIP) is a lethal immune-related adverse event. However, the development process of CIP, which may provide insight into more effective management, has not been extensively examined.MethodsWe conducted a multicenter retrospective analysis of 56 patients who developed CIP. Clinical characteristics, radiological features, histologic features, and laboratory tests were analyzed. After a comprehensive analysis, we proposed acute, subacute, and chronic phases of CIP and summarized each phase’s characteristics.ResultsThere were 51 patients in the acute phase, 22 in the subacute phase, and 11 in the chronic phase. The median interval time from the beginning of CIP to the different phases was calculated (acute phase: ≤4.9 weeks; subacute phase: 4.9~13.1 weeks; and chronic phase: ≥13.1 weeks). The symptoms relieved from the acute phase to the chronic phase, and the CIP grade and Performance Status score decreased (P<0.05). The main change in radiologic features was the absorption of the lesions, and 3 (3/11) patients in the chronic phase had persistent traction bronchiectasis. For histologic features, most patients had acute fibrinous pneumonitis in the acute phase (5/8), and most had organizing pneumonia in the subacute phase (5/6). Other histologic changes advanced over time, with the lesions entering a state of fibrosis. Moreover, the levels of interleukin-6, interleukin-10 and high-sensitivity C-reactive protein (hsCRP) increased in the acute phase and decreased as CIP progressed (IL-6: 17.9 vs. 9.8 vs. 5.7, P=0.018; IL-10: 4.6 vs 3.0 vs. 2.0, P=0.041; hsCRP: 88.2 vs. 19.4 vs. 14.4, P=0.005).ConclusionsThe general development process of CIP can be divided into acute, subacute, and chronic phases, upon which a better management strategy might be based devised

Application of next-generation sequencing on diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with ANCA-associated vasculitis

Abstract Background Mycoplasma hominis is one of the main opportunistic pathogenic mycoplasmas in humans which has a major impact on patients with bloodstream infections. Because it is difficult to detect or isolate, rapid and accurate diagnosis using improved methods is essential and still challenging for patients with bloodstream infection. Case presentation In this case, we reported the application of next -generation sequencing for the diagnosis of bloodstream infection caused by Mycoplasma hominis in a patient with Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. After 9 days of combined treatment with levofloxacin, polymyxin B and meropenem, the patient’s condition was gradually controlled and he was discharged without further complications. During the three-month outpatient follow-up, no recurrence of symptoms or clinical signs was reported. Conclusions This successful application of next generation sequencing assisted the rapid diagnosis of Mycoplasma hominis bloodstream infection, provided a new perspective in the clinical approach and highlighted the potential of this technique in rapid etiological diagnosis

Elevation of Plasma Homocysteine and Minor Hallucinations in Parkinson’s Disease: A Cross-Sectional Study

Purpose. Minor hallucinations (MHs) are the most common psychotic phenomena in Parkinson’s disease (PD), and it has important clinical and prognostic implications in PD. Plasma homocysteine (Hcy) has been reported to predict the outcome of PD; whether or not Hcy is associated with MH is not known. We aim to investigate the Hcy level and related factors in patients with PD and MH. Methods. We conducted a cross-sectional study and included 99 patients with PD, 34 with MH, and 65 without any hallucinations. The clinical and demographic data of the patients with and without hallucinations were compared. Hcy-related clinical factors were also analyzed. Results. The plasma Hcy level was higher in MH patients than in patients without hallucinations, and the result was more pronounced in male patients than in female patients. Differences were also observed when the groups were divided on the basis of levodopa equivalent daily dose and disease duration. The high Hcy concentration was correlated with some symptoms in patients with MH, including motor dysfunction and nonmotor symptoms, such as symptoms of the gastrointestinal tract, angiocarpy, sleep/fatigue, and poor visuospatial/executive function. Conclusions. Results indicated a higher plasma Hcy concentration in MH patients than in their counterparts and revealed that Hcy is associated with certain motor and nonmotor symptoms in patients with MH. Hcy may be a marker of MH and have important therapeutic implications in PD.Peer Reviewe

Clinical efficacy of combined sodium dimercaptopropanesulfonate and zinc treatment in neurological Wilson’s disease with D-penicillamine treatment failure

Objectives: There are limited pharmacological treatments for patients with neurological Wilson’s disease (WD) and a history of copper-chelating treatment failure. Methods: We retrospectively evaluated the clinical records of 38 patients with WD who were treated with sodium dimercaptopropanesulfonate (DMPS) and zinc (group 1) or zinc alone (group 2). All patients had a history of neurological deterioration during their previous treatment with D-penicillamine (DPA). Results: Twenty-one patients were treated with intravenous DMPS for 4 weeks, followed by zinc gluconate for 6 months, and the treatment protocol was repeated twice. Relative to the baseline, repeated DMPS therapy and zinc maintenance therapy decreased neurological scores continuously ( p < 0.01). Sixteen patients (76.2%) demonstrated neurological improvements after 1 year of therapy and four patients (19.0%) exhibited neurological deterioration at the follow-up session. In addition, 17 patients were treated with zinc monotherapy for 12 months. Two patients (11.8%) demonstrated neurological improvements and five patients (29.4%) exhibited neurological deterioration. Compared with the patients in group 2, a greater improvement ratio ( p < 0.01) and lower deterioration ratio ( p < 0.01) were observed in the patients in group 1 after 1 year of therapy. Conclusions: Our findings indicate that the safety and efficacy of combined treatment of DMPS and zinc is superior to those of zinc monotherapy in patients with neurological WD with a history of DPA treatment failure

Gait Analysis with Wearables Is a Potential Progression Marker in Parkinson&rsquo;s Disease

Gait disturbance is a prototypical feature of Parkinson&rsquo;s disease (PD), and the quantification of gait using wearable sensors is promising. This study aimed to identify gait impairment in the early and progressive stages of PD according to the Hoehn and Yahr (H&ndash;Y) scale. A total of 138 PD patients and 56 healthy controls (HCs) were included in our research. We collected gait parameters using the JiBuEn gait-analysis system. For spatiotemporal gait parameters and kinematic gait parameters, we observed significant differences in stride length (SL), gait velocity, the variability of SL, heel strike angle, and the range of motion (ROM) of the ankle, knee, and hip joints between HCs and PD patients in H&ndash;Y &#8544;-&#8545;. The changes worsened with the progression of PD. The differences in the asymmetry index of the SL and ROM of the hip were found between HCs and patients in H&ndash;Y &#8547;. Additionally, these gait parameters were significantly associated with Unified Parkinson&rsquo;s Disease Rating Scale and Parkinson&rsquo;s Disease Questionnaire-39. This study demonstrated that gait impairment occurs in the early stage of PD and deteriorates with the progression of the disease. The gait parameters mentioned above may help to detect PD earlier and assess the progression of PD

ERRα negatively regulates type I interferon induction by inhibiting TBK1-IRF3 interaction

<div><p>Estrogen-related receptor α (ERRα) is a member of the <a href="http://en.wikipedia.org/wiki/Nuclear_receptor" target="_blank">nuclear receptor</a> superfamily controlling energy homeostasis; however, its precise role in regulating antiviral innate immunity remains to be clarified. Here, we showed that ERRα deficiency conferred resistance to viral infection both <i>in vivo</i> and <i>in vitro</i>. Mechanistically, ERRα inhibited the production of type-I interferon (IFN-I) and the expression of multiple interferon-stimulated genes (ISGs). Furthermore, we found that viral infection induced TBK1-dependent ERRα stabilization, which in turn associated with TBK1 and IRF3 to impede the formation of TBK1-IRF3, IRF3 phosphorylation, IRF3 dimerization, and the DNA binding affinity of IRF3. The effect of ERRα on IFN-I production was independent of its transcriptional activity and PCG-1α. Notably, ERRα chemical inhibitor XCT790 has broad antiviral potency. This work not only identifies ERRα as a critical negative regulator of antiviral signaling, but also provides a potential target for future antiviral therapy.</p></div

ERRα is stabilized by viral infection.

<p>(A-E) Immunoblotting analysis of ERRα protein expression in 293T (A), BMDMs (B), THP-1(C), MEFs (D), and HeLa (E) infected with VSV (MOI = 1.0) for the indicated times. α-Tubulin was used as the equal loading control. (F-G) Immunoblotting analysis of ERRα protein expression in THP-1 cells infected with HSV (F) or incubated with 100 ng/ml LPS (G) for the indicated times. α-Tubulin was used as the equal loading control. (H) Immunoblotting analysis of ERRα protein expression from tissues of VSV-infected C57BL/6 mice collected at the indicated time points (n = 3 per group). α-Tubulin was used as the equal loading control. (I) Immunoblotting analysis of fractionated 293T cells infected with VSV for the indicated times. Cyt, cytosolic; Nuc, nuclear. The purity of the fractions was assessed by blotting for Lamin A (nuclear protein) and α-Tubulin (cytosolic protein). (J) qRT-PCR analysis of ERRα mRNA expression in 293T cells infected with VSV (MOI = 1.0) for the indicated times. The data were normalized to the expression of the β-actin reference gene. Cell-based studies were performed independently at least three times with comparable results. The data are presented as the means ± SEM.</p