Epidemiology,clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: Data from 151 patients

FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n = 84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99-1,03]; P = .05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; P = .004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM.     

Neuroprotective effect of Crocus sativus against cerebral ischemia in rats

Metabolic Brain Disease - The present study aimed to investigate the role of vascular endothelial growth factor (VEGF) in the neuroprotective effect of Crocus sativus (saffron) against cerebral...     

Childhood Verbal Abuse: A Risk Factor for Depression in Pre-Bariatric Surgery Psychological Evaluations

The present study evaluated the importance of multimodal assessment of childhood verbal abuse (CVA) in pre-bariatric surgery psychological evaluations, and the role of CVA as a predictor of depression. Data from the psychological evaluations of 184 pre-bariatric surgery patients were retrospectively examined. Using two self-report measures and an interview-based screen, 52.2 % of participants reported experiencing some form of CVA; conversely, assessments of CVA based on only one measure yielded significantly lower prevalence rates. Endorsement of CVA on multiple measures was associated with more severe depressive symptomatology and greater likelihood of mood disorder diagnosis. Based on these data, a self-report measure and interview-based screen for CVA should be included in pre-bariatric psychological evaluations; either of these assessments may be conducted via a single-item screen. Lastly, patients who endorse CVA on multiple measures should be monitored closely for symptoms of depression post-surgery.     

Resilience and Mental Health in Adult Survivors of Child Abuse Associated with the Institution of the Austrian Catholic Church

In recent years, reports of institutional abuse within the Catholic Church have emerged and research on the consequences on mental health is in its beginnings. In this study, we report findings on current mental health and resilience in a sample of adult survivors of institutional abuse (N = 185). We compared 3 groups of survivors that differed regarding their current mental health to investigate aspects of resilience, coping, and disclosure. The majority of the sample was male (76.2%), the mean age was 56.28 (SD = 9.46) years, and more than 50.0% of the sample was cohabiting/married. Most of the survivors reported severe mental health problems. Known protective factors (education, social support, age) were not associated with mental health in our sample. Our findings corroborate that institutional abuse has long‐term effects on mental health. We found that fewer emotional reactions during disclosure, task‐oriented coping, and optimism were associated with better mental health. The study was limited by a cross‐sectional design, but we conclude that the kind of institutional abuse reported is especially adverse, and thus typical protective factors for mental health do not apply. Future research should focus on intrapersonal factors and institutional dynamics to improve treatment for persons affected by institutional abuse.     

Equivalence and measurement properties of an electronic version of the Psoriasis Symptom Inventory

Purpose

To evaluate the equivalence of electronic and paper versions of the Psoriasis Symptom Inventory and to examine measurement properties of the electronic version.

Methods

In a prospective, randomized, crossover, non-interventional study in adult subjects (age ≥18 years) with plaque psoriasis conducted over a period of 15 days, subjects were randomized to two groups, completing either the paper or electronic Psoriasis Symptom Inventory daily for 7 consecutive days followed by the alternate version. Equivalence was assessed by the intraclass correlation coefficient (ICC) between both administration modes. Differences in scores were also tested using paired Student’s t test. Measurement properties included internal consistency reliability, test–retest reliability, and convergent and discriminant validity between the Psoriasis Symptom Inventory and (1) disease-specific (Dermatology Life Quality Index) and (2) general health (SF-36v2) status.

Results

Eighty subjects [74 % (59/80) moderate-to-severe psoriasis; 26 % (21/80) mild psoriasis receiving systemic treatment] were enrolled from 8 sites in the USA. The two modes were highly concordant for both total (ICC = 0.97) and individual item scores (ICC range = 0.93–0.97). Response bias testing showed no differences based on completion order with all ICC values >0.91. All mean score differences, except for one item (“flaking”), were non-significant (P > 0.05). Minimum values for reliability (>0.70) and validity (convergent, r ≥ 0.40) were exceeded for the electronic Psoriasis Symptom Inventory.

Conclusions

Equivalence between paper and electronic versions of the Psoriasis Symptom Inventory and strong measurement properties of the electronic mode indicated a successful migration from paper to electronic format of the Psoriasis Symptom Inventory.     

Depression and painful conditions: patterns of association with health status and health utility ratings in the general population

Purpose

Preference-weighted HRQoL (utility) ratings are increasingly used to guide clinical and resource allocation decisions, but their performance has not always been adequately explored. We sought to examine patterns of health utility ratings in community populations with depressive disorders and painful conditions.

Methods

We used two Canadian cross-sectional health surveys that obtained Comprehensive Health Status Measurement System/Health Utilities Index Mark 3 (HUI3) ratings and identified people with painful conditions and major depression. We estimated the frequency of item endorsements and mean utility ratings in these groups.

Results

Interesting differences between health state ratings and diagnostic categories were noted. For example, 71 % of those professionally diagnosed with migraine reported that they usually have “no pain.” Despite this, utility ratings were lower in those respondents with depressive episodes and in those with painful conditions. Greater than additive reductions in HUI3 scores were noted in most instances where both depressive disorders and painful conditions were present.

Conclusions

Health utility ratings confirm the clinical impression that painful conditions and depressive disorders magnify each other’s impact. Despite weak alignment between the health state definitions incorporated into utility ratings and the diagnostic concepts examined, the HUI3 appeared to capture HRQoL decrements and negative synergies associated with the co-occurrence of depressive episodes and painful conditions.     

Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM⁺ and IgM⁻ plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.     

Topoisomerase II-alfa gene as a predictive marker of response to anthracyclines in breast cancer

Amplification or deletion of the topoisomerase IIα (TOP2A) gene in breast cancer has been related with responsiveness to anthracyclines-based chemotherapy. The purpose of this study was to evaluate the predictive value of TOP2A gene for the efficacy of neo-adjuvant anthracycline in a population with locally advanced breast cancer. Sixty-two patients were included, and the status of TOP2A gene was determined by in situ hybridization method. Treatment efficacy was determined by clinical and pathological response and overall survival. TOP2A gene alterations were found in 22.6% (21.0% of cases with amplification and 1.6% with deletion), and these tumors were biologically more aggressive, with higher nuclear grade, more frequently with HER2 amplification and inflammatory type. Also in these tumors response to chemotherapy appeared to be increased. There was a higher clinical and pathological response rate (complete pathological response of 21.4% vs. 8.3%), a trend toward longer progression-free survival (82.51 vs. 63.12 months) and a trend to increased overall survival (92.08 months; 95% CI 82.81–101.35 vs. 73.40 months; 95% CI 63.44–83.36; p = 0.113). These results corroborate that the TOP2A gene alterations may play an important role in determining anthracycline sensitivity in breast cancer.     

Estrogen receptor alpha and androgen receptor are commonly expressed in well-differentiated liposarcoma

Background

Liposarcoma (LS) is the second-most common type of soft-tissue sarcoma. Despite advances in knowledge and treatment of this disease, there remains a need for more effective LS therapy. Steroid hormone receptors regulate metabolism in adipocytes. Estrogen receptor alpha (ER), progesterone receptor (PR), and androgen receptor (AR) have been implicated in the pathophysiology of other cancer types. We sought to comprehensively determine temporal expression patterns of these receptors in LS.

Methods

We analyzed 561 histologically subtyped LS specimens from 354 patients for expression of ER, PR, and AR by immunohistochemistry (IHC) using diagnostic-grade reagents and protocols. The fractions of positively stained tumor cells were scored within each specimen. IHC scores were compared across LS subtypes using the Kruskal-Wallis test, and subtypes were compared using Dunn’s post-hoc test. Ages of patients with receptor-positive vs. -negative LS were compared by t-test. Genders and races were compared for hormone receptor positivity using Fisher’s exact test and Chi-square analysis, respectively. Recurrence-free survival was compared between receptor-positive and negative patients by log-rank test. p<?0.05 was considered significant.

Results

ER and AR were frequently expressed in LS, while few tumors expressed PR. Most of the ER?+?and AR?+?samples were of the well-differentiated LS subtype. A smaller fraction of de-differentiated LS expressed ER or AR, but expression was common within well-differentiated regions of tumors histologically classified as de-differentiated LS. In LS specimens from patients who underwent multiple surgeries over time, receptor expression frequently changed over time, which may be attributable in part to intratumor heterogeneity, varying degrees of de-differentiation, and biopsy bias. ER and AR were frequently co-expressed. Receptor status was not significantly associated with gender or race, but AR and PR expression were associated with earlier age at diagnosis. Receptor expression was not associated with altered recurrence-free survival.

Conclusions

ER and AR are commonly expressed in LS, particularly in well-differentiated tumors. These data warrant further functional study to determine receptor function in LS, and the potential efficacy of anti-hormone therapies for the treatment of patients with LS.