Detection of clonotypic DNA in the cerebrospinal fluid as a marker of central nervous system invasion in lymphoma

Diagnosis of parenchymal central nervous system (CNS) invasion and prediction of risk for future CNS recurrence are major challenges in the management of aggressive lymphomas, and accurate biomarkers are needed to supplement clinical risk predictors. For this purpose, we studied a next-generation sequencing (NGS)-based assay that detects tumor-derived DNA for clonotypic immunoglobulin gene rearrangements in the cerebrospinal fluid (CSF) of patients with lymphomas. Used as a diagnostic tool, the NGS-MRD assay detected clonotypic DNA in 100% of CSF samples from 13 patients with known CNS involvement. These included 7 patients with parenchymal brain disease only, whose CSF tested negative by standard cytology and flow cytometry, and 6 historical DNA aliquots collected from patients at median 39 months prior to accession, which had failed to show clonal rearrangements using standard polymerase chain reaction. For risk prognostication, we prospectively collected CSF from 22 patients with newly diagnosed B-cell lymphomas at high clinical risk of CNS recurrence, of whom 8 (36%) had detectable clonotypic DNA in the CSF. Despite intrathecal prophylaxis, a positive NGS-MRD assay in the CSF was associated with 29% cumulative risk of CNS recurrence within 12 months from diagnosis, in contrast with 0% risk among patients with a negative assay (P=0.045). These observations suggest that detection of clonotypic DNA can aid in diagnosis of suspected parenchymal brain recurrence in aggressive lymphoma. Furthermore, the NGS-MRD assay might enhance clinical risk assessment for CNS recurrence among newly diagnosed patients and help select those who might benefit most from novel approaches to CNS-directed prophylaxis.

Application of the 21-Gene Recurrence Score in Patients with Early HR-Positive/HER2-Negative Breast Cancer: Chemotherapy and Survival Rate According to Clinical Risk

We assessed the impact of 21-gene Recurrence Score (RS) assay on chemotherapy decision-making according to binary clinical risk stratification in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. We included patients with tumors measuring 1–5 cm, N0-1, and HR+/HER2- breast cancer who underwent surgery followed by adjuvant treatment. The clinical risk was determined by a modified version of Adjuvant! Online. We performed propensity score matching (PSM) according to the application of 21-gene RS separately in the low and high clinical risk groups. Before PSM, 342 (39.0%) of 878 patients were classified as having high clinical risk. In the high clinical risk group, 21-gene RS showed a significantly reduced chemotherapy rate of 39.3%, without increasing the recurrence. After PSM, the 21-gene RS application significantly reduced chemotherapy rate by 34.0% in 200 patients with high clinical risk (21-gene RS application, 32.0% vs. no 21-gene RS application, 66.0%, p < 0.001). There was also no significant difference in RFS according to 21-gene RS status in the high clinical risk group (log-rank test, p = 0.467). These results support the usefulness of the 21-gene RS to reduce the chemotherapy rate without adversely affecting prognosis in a high clinical risk group.

Hydroxychloroquine and Azithromycin Treatment of Hospitalized Patients Infected with SARS-CoV-2 in Senegal from March to October 2020

As of today, little data is available on COVID-19 in African countries, where the case management relied mainly on a treatment by association between hydroxychloroquine (HCQ) and azithromycin (AZM). This study aimed to understand the main clinical outcomes of COVID-19 hospitalized patients in Senegal from March to October 20202. We described the clinical characteristics of patients and analysed clinical status (alive and discharged versus hospitalized or died) at 15 days after Isolation and Treatment Centres (ITC) admission among adult patients who received HCQ plus AZM and those who did not receive this combination. A total of 926 patients were included in this analysis. Six hundred seventy-four (674) (72.8%) patients received a combination of HCQ and AZM. Results showed that the proportion of patient discharge at D15 was significantly higher for patients receiving HCQ plus AZM (OR: 1.63, IC 95% (1.09–2.43)). Factors associated with a lower proportion of patients discharged alive were: age ≥ 60 years (OR: 0.55, IC 95% (0.36–0.83)), having of at least one pre-existing disorder (OR: 0.61, IC 95% (0.42–0.90)), and a high clinical risk at admission following NEWS score (OR: 0.49, IC 95% (0.28–0.83)). Few side effects were reported including 2 cases of cardiac rhythmic disorders in the HCQ and AZM group versus 13 in without HCQ + AZM. An improvement of clinical status at 15 days was found for patients exposed to HCQ plus AZM combination.

Thrombin Generation as a Method to Identify the Risk of Bleeding in High Clinical-Risk Patients Using Dual Antiplatelet Therapy

Background: Patients using dual antiplatelet therapy after percutaneous coronary intervention are at risk for bleeding. It is currently unknown whether thrombin generation can be used to identify patients receiving dual antiplatelet therapy with increased bleeding risk.Objectives: To investigate whether thrombin generation measurement in plasma provides additional insight into the assessment of bleeding risk for high clinical-risk patients using dual antiplatelet therapy.Methods: Coagulation factors and thrombin generation in platelet-poor plasma were measured in 93 high clinical-risk frail patients using dual antiplatelet therapy after percutaneous coronary intervention. During 12-month follow-up, clinically relevant bleedings were reported. Thrombin generation at 1 and 6 months after percutaneous coronary intervention was compared between patients with and without bleeding events.Results: One month after percutaneous coronary intervention, the parameters of thrombin generation, endogenous thrombin potential, peak height, and velocity index were significantly lower in patients with bleeding in the following months compared to patients without bleeding. At 6 months follow-up, endogenous thrombin potential, peak height, and velocity index were still (significantly) decreased in the bleeding group as compared to non-bleeders. Thrombin generation in the patients' plasma was strongly dependent on factor II, V, and VIII activity and fibrinogen.Conclusion: High clinical-risk patients using dual antiplatelet therapy with clinically relevant bleeding during follow-up show reduced and delayed thrombin generation in platelet-poor plasma, possibly due to variation in coagulation factors. Thus, impaired thrombin-generating potential may be a “second hit” on top of dual antiplatelet therapy, increasing the bleeding risk in high clinical-risk patients. Thrombin generation has the potential to improve the identification of patients using dual antiplatelet therapy at increased risk of bleeding.

Unrealistic Optimism and Risk for COVID-19 Disease

Risk perception and consequently engagement in behaviors to avoid illness often do not match actual risk of infection, morbidity, and mortality. Unrealistic optimism occurs when individuals falsely believe that their personal outcomes will be more favorable than others' in the same risk category. Natural selection could favor overconfidence if its benefits, such as psychological resilience, outweigh its costs. However, just because optimism biases may have offered fitness advantages in our evolutionary past does not mean that they are always optimal. The current project examined relationships among personal risk for severe COVID-19, risk perceptions, and preventative behaviors. We predicted that those with higher risk of severe COVID-19 would exhibit unrealistic optimism and behave in ways inconsistent with their elevated risk of morbidity and mortality. Clinical risk scores for severe COVID-19 were calculated and compared with COVID-19 threat appraisal, compliance with shelter-in-place orders (March 13–May 22, 2020) and travel restrictions, compliance with public health recommendations, and potential covariates like self-rated knowledge about COVID-19 in a robust dataset including 492 participants from McLennan County, TX, USA. While those with high clinical risk acknowledged their greater likelihood of experiencing severe illness if infected, they actually reported lower perceived likelihood of becoming infected in the first place. While it is possible that those with higher clinical risk scores truly are less likely to become infected, the pattern and significance of these results held after controlling for possible occupational exposure, household size, and other factors related to infection probability. Higher clinical risk also predicted more recent travel within Texas and lower distress during the pandemic (i.e., feeling less stressed, depressed, and helpless). Additional behavioral data suggested that those with higher clinical risk scores did not generally behave differently than those with lower scores during the shelter-in-place order. While unrealistic optimism may provide some short-term psychological benefits, it could be dangerous due to improper assessment of hazardous situations; inferring that optimism bias has evolutionary origins does not mean that unrealistic optimism is “optimal” in every situation. This may be especially true when individuals face novel sources (or scales) of risk, such as a global pandemic.

BASIC SYMPTOM AND THE PREDICTION OF CLINICAL HIGH RISK ON PSYCHOSIS

The possibility of providing interventions before the onset of the acute psychotic phase has become the international community’s focus as an early intervention in this disorder. One criterion that is important to diagnoses a high-risk clinical state on psychosis is an basic symptom. Understanding the basic symptom will increase the understanding of the symptoms in individuals with a high risk of psychosis. This literature review aims to review the basic symptoms and empirical evidence that has been carried out by previous studies that show how basic symptom criteria can predicting a high clinical risk of psychosis. Database search using database system in Pubmed and Proquest for the article year 2000 to 2020. Keyword search for the following terms are (basic symptom) AND (high clinical risk). The pieces are limited to the population of ages 15 – 30 years. For this, database-provided age-limit filters and a filter based on the following search terms will be used: [(young people-related words) OR (young adult-related terms)]. The data extraction results found seven articles out of 128 pieces, excluding 41 full-text articles that were not accessible and 79 articles that were not relevant. The use of basic symptom criteria, including COGNIS and COPER, has been shown to predict future conversion to psychosis with a high sensitivity level, above 0.5 or even 0.98. The COGDIS criteria were able to predict first-episode psychosis. However, some studies suggest an increase in predictive accuracy when using the UHR and COGDIS criteria, while using one of these criteria will increase sensitivity. If early detection can help the seeking population, the onset of psychosis can be delayed.

Transferring MINDACT to Daily Routine: Implementation of the 70-Gene Signature in Luminal Early Breast Cancer – Results from a Prospective Registry of the Austrian Group Medical Tumor Therapy (AGMT)

<b><i>Background:</i></b> For hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC), adjuvant chemotherapy (ACT) is recommended in the case of high-risk features only. The MINDACT trial showed that patients with high clinical risk (CR) but low genomic risk (GR) defined by the 70-gene signature (MammaPrint®; 70-GS) did not benefit from ACT. In this registry, we investigated the frequency and feasibility of 70-GS and concurrent 80-gene subtyping (BluePrint®) use in HR-positive, HER2-negative EBC. Furthermore, we recorded the frequency of ACT recommendation and the adherence to it when the “MINDACT strategy” was used. <b><i>Methods:</i></b> This prospective registry included patients from 2 Austrian cancer centers. Similar to MINDACT, a modified version of Adjuvant!Online was used to determine CR, and 70-GC was used to determine GR in high-CR patients. ACT was recommended to patients with high CR and high GR. <b><i>Results:</i></b> Of 224 enrolled patients, 76 (33.9%) had high CR and 67 (88.2%) received genomic testing. Of those, 43 (64.2%) were classified as low and 24 (35.8%) as high GR, respectively. All 24 patients with high CR and GR (10.7% of all patients) received the recommendation for ACT, but ACT was started in only 15 patients (62.5%). The median time from surgery to the start of ACT was 45 days (range 32–68), and the median time from test decision to the test result was 15 days (range 9–56). <b><i>Conclusion:</i></b> We showed that the results of the MINDACT trial are reproducible in an Austrian population. Incorporating 70-GS into the daily clinical routine is feasible and mostly accepted by physicians for the guidance of treatment recommendations.

Emotional Response to Humour Perception and Gelotophobia Among Healthy Individuals and Patients with Schizophrenia and Depression, with Signs of a High Clinical Risk of Psychosis

Introduction. Investigating early changes in the emotional sphere within the schizophrenia course is a perspective direction in clinical psychology and psychiatry. Intactness of positive emotions, in particular, humour perception, may be a very important resource for patients. At the same time, humour perception is very sensitive to pathological conditions, such as the fear of being laughed at, known as gelotophobia. Those with gelotophobia perceive laughter as dangerous, rather than pleasant, and they can hardly distinguish between teasing and ridicule. Gelotophobia was confirmed to be expressed among people with mental disorders. Nonetheless, knowledge relating to the fear of being laughed at, was mostly generated among the non-clinical samples. Objectives. Thus, the aim of the study was to provide more clinical data on gelotophobia manifestations associated with schizophrenia spectrum disorders; the emotional response and facial expression of patients with gelotophobia were studied, in particular, regarding their perception of humour, including during the early stages of disorders, by comparison with healthy individuals. Methods. n=30 controls and n=32 patients with schizophrenia and with depression with signs of a high clinical risk of psychosis took part. Two short videos, comic and neutral, were shown to the participants, while videotaping their facial expression, followed each by a self-reported measure of emotional responses. Participants also completed the State-Trait Anxiety Inventory, the PhoPhiKat30 and the Toronto Alexithymia Scale. Results. Gelotophobia was significantly higher within the clinical group. It correlated with a lower frequency of grins among the patients during the comic video, while this was not the case in the control group. Gelotophobia was related to state and trait anxiety in both groups, but only in the clinical group did state anxiety increase after watching the comic video. Gelotophobia correlated with alexithymia and was twice higher among the patients compared to the controls. Conclusion. Thus, gelotophobia has not only quantitative, but also qualitative specifics in patients with schizophrenia, and those with depression with signs of a clinically high risk of psychosis, compared to healthy controls.