Enhancing hematopathology peripheral blood smear education through asynchronous video material: A pilot report.

This study explores the effectiveness of asynchronous video material as a supplementary educational tool for trainees in hematopathology. Traditional pedagogical methods often rely heavily on faculty involvement, potentially limiting the breadth of information trainees receive due to constraints in faculty time and the variety of cases covered in a limited time interval/rotation. Asynchronous video-based learning presents a potential solution to these challenges. This concept has been utilized effectively in various fields of medical education. In this study, we describe our implementation of an educational program utilizing asynchronous video material to supplement traditional learning methods for peripheral blood smear interpretation for learners on a hematopathology clerkship. Following a pre-test/post-test assessment with 13 trainees, we analyzed the correlation between video viewing percentage and changes in test scores. The results indicate an improvement in test scores following exposure to video content, supporting the positive impact of asynchronous video material on hematopathology education. Trainees had positive feedback regarding this new educational tool. This study suggests that such self-directed learning could enhance traditional teaching methods, ensuring broader and more consistent coverage of hematopathology concepts.

[Participation-oriented psychotherapy for patients with mental disorders who are able or unable to work : Results of a survey of practicing psychotherapists]. / Teilhabeorientierte Psychotherapie bei arbeitsfähigen und arbeitsunfähigen Patienten mit psychischen Erkrankungen : Ergebnisse einer Befragung niedergelassener Psychotherapeuten.

BACKGROUND: Treatment of (chronic) mental disorders must focus on both reducing symptoms and improving social and work participation by social medicine treatments and counselling. The objective of this study was to compare psychotherapy patients who are fit or unfit for work to describe similarities and differences regarding patient status and interventions. METHODS: Interviews were performed with 73 cognitive behavior therapists and 58 psychodynamic psychotherapists about 188 and 134 recent cases they had seen, respectively. The case reports referred to patients who were on average 42 years old (65% females). RESULTS: There were no differences between patients with no or short-term sick leave (up to 6 weeks, n = 156) and patients with longer sick leave (7 weeks or more, n = 140) with respect to basic characteristics of treatment (side effects, therapeutic alliance). Patients with a longer sick leave duration had more severe capacity and participation impairments and received more specific work participation-oriented treatments, whereas general saluto-therapeutic activities (sports-club, counselling, family-support) were similarly undertaken in patients with shorter or longer sick leave. DISCUSSION: Therapists chose intervention options according to indication: in patients with work participation problems, more work-related treatments are undertaken, whereas interventions for general mental health improvement are distributed independent of specific work participation problems.

Early Life Stress Is Associated with Alterations in Lymphocyte Subsets Independent of Increased Inflammation in Adolescents.

Early life stress (ELS) is linked to an elevated risk of poor health and early mortality, with emerging evidence pointing to the pivotal role of the immune system in long-term health outcomes. While recent research has focused on the impact of ELS on inflammation, this study examined the impact of ELS on immune function, including CMV seropositivity, inflammatory cytokines, and lymphocyte cell subsets in an adolescent cohort. This study used data from the Early Life Stress and Cardiometabolic Health in Adolescence Study (N = 191, aged 12 to 21 years, N = 95 exposed to ELS). We employed multiple regression to investigate the association between ELS, characterized by early institutional care, cytomegalovirus (CMV) seropositivity (determined by chemiluminescent immunoassay), inflammation (CRP, IL-6, and TNF-a determined by ELISA), and twenty-one immune cell subsets characterized by flow cytometry (sixteen T cell subsets and five B cell subsets). Results reveal a significant association between ELS and lymphocytes that was independent of the association between ELS and inflammation: ELS was associated with increased effector memory helper T cells, effector memory cytotoxic T cells, senescent T cells, senescent B cells, and IgD- memory B cells compared to non-adopted youth. ELS was also associated with reduced percentages of helper T cells and naive cytotoxic T cells. Exploratory analyses found that the association between ELS and fewer helper T cells and increased cytotoxic T cells remained even in cytomegalovirus (CMV) seronegative youth. These findings suggest that ELS is associated with cell subsets that are linked to early mortality risk in older populations and markers of replicative senescence, separate from inflammation, in adolescents.

Injustice and Embitterment: Crucial Stressors in Psychosomatic Patients.

OBJECTIVE: "Disorders specifically associated with stress" are receiving increasing attention in clinical practice, research, and modern classification systems of mental disorders. This includes not only reactions to "extremely threatening or horrific events" as it is characteristic for "post-traumatic stress disorders" but also a variety of day-to-day experiences. Examples are experiences of injustice, humiliation, or breach of trust which can have dire psychological consequences such as feelings of embitterment, a strong and crippling emotion. This study investigated the frequency of feelings of injustice and concomitant embitterment across different areas of daily life of psychosomatic patients. METHODS: In an observational archival study, 200 inpatients of a department of behavioral medicine filled in the "Differential Life Burden Scale, DLB-Scale" and the "Post-Traumatic Embitterment Scale, PTED-Scale" which asks for experiences of injustice and embitterment. RESULTS: More than half of all patients (58.5%) reported about very or extremely unjust and unfair life events and 51.5% additionally about feelings of embitterment. This was primarily associated with complaints about problems in the family and the workplace and was accompanied by an impairment of well-being. CONCLUSIONS: The findings indicate that experiences of injustice and embitterment are frequently seen in psychosomatic inpatients and should get special attention.

Digital and manual interfollicular Ki-67 are associated with a progression-free survival in patients with low-grade follicular lymphoma.

OBJECTIVES: Novel histopathologic prognostic factors are needed to identify patients with follicular lymphoma (FL) at risk of inferior outcomes. Our primary objective was to evaluate the Ki-67 proliferative index in follicular and interfollicular areas in tissue biopsy specimens from patients with newly diagnosed FL and correlate with clinical outcomes. Our secondary objective was to correlate PD-L1 and LAG-3 with clinical outcomes. METHODS: Seventy cases of low-grade FL from the University of Minnesota were evaluated with Ki-67 immunohistochemical stain. Ki-67 expression as a continuous variable was interpreted digitally and manually in follicular and interfollicular areas. Progression-free survival (PFS) and overall survival (OS) were analyzed by Cox regression, and hazard ratios (HRs) per 10-point increase in Ki-67 were calculated. RESULTS: Progression-free survival at 4 years was 28% (95% CI, 19%-41%). Interfollicular, but not follicular, Ki-67 was associated with PFS by manual (HR, 1.33; P = .01) and digital (HR, 1.38; P = .02) analysis. Digital and manual Ki-67 were only moderately correlated but demonstrated similar effects on PFS. At 4 years, OS was 90% with no association with follicular or interfollicular Ki-67 proliferation. CONCLUSIONS: Higher interfollicular Ki-67 by either digital or manual analysis is associated with a poorer PFS in patients with low-grade FL. These results suggest further validation of this marker is warranted to improve pathologic risk stratification at FL diagnosis. PD-L1 and LAG-3 were not associated with PFS or OS.

Patients' perception of side effects in cognitive-behavior, psychodynamic, and psychoanalytic outpatient psychotherapy.

OBJECTIVE: To assess and compare the frequency of psychotherapeutic side effects in different psychotherapeutic approaches. METHOD: Side effects were assessed across 17 domains through structured interviews with 45 outpatients in cognitive-behavior, psychodynamic, and psychoanalytic psychotherapy. RESULTS: Almost every patient (95.6%) reported at least one side effect, with a mean of 4.7 affected domains. Most frequent complaints were that problems were seen as more complex (60.0-80.0%), worsening of pre-existing symptoms (46.7-60%), occurrence of new symptoms (20.0-53.3%), feeling uncomfortable in treatment (33.3-40.0%), tensions with therapist (26.7-46.7%), as well as conflicts with current family and with family of origin (both 13.3-46.7%). Differences between therapeutic orientations were mostly non-significant. CONCLUSION: Psychotherapy is regularly accompanied by side effects, independent of different theoretical orientations. Psychotherapists need to be familiar with side effects in order to inform patients about treatment-associated risks and to recognize and manage side effects.

Perinatal folate levels do not influence tumor latency or multiplicity in a model of NF1 associated plexiform-like neurofibromas.

OBJECTIVE: In epidemiological and experimental research, high folic acid intake has been demonstrated to accelerate tumor development among populations with genetic and/or molecular susceptibility to cancer. Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder predisposing affected individuals to tumorigenesis, including benign plexiform neurofibromas; however, understanding of factors associated with tumor risk in NF1 patients is limited. Therefore, we investigated whether pregestational folic acid intake modified plexiform-like peripheral nerve sheath tumor risk in a transgenic NF1 murine model. RESULTS: We observed no significant differences in overall survival according to folate group. Relative to controls (180 days), median survival did not statistically differ in deficient (174 days, P = 0.56) or supplemented (177 days, P = 0.13) folate groups. Dietary folate intake was positively associated with RBC folate levels at weaning, (P = 0.023, 0.0096, and 0.0006 for deficient vs. control, control vs. supplemented, and deficient vs. supplemented groups, respectively). Dorsal root ganglia (DRG), brachial plexi, and sciatic nerves were assessed according to folate group. Mice in the folate deficient group had significantly more enlarged DRG relative to controls (P = 0.044), but no other groups statistically differed. No significant differences for brachial plexi or sciatic nerve enlargement were observed according to folate status.

PCNEO, a New Proficiency Testing Program for Flow Cytometric Analysis of Plasma Cell Neoplasms From the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee.

CONTEXT.­: In 2018 the College of American Pathologists Diagnostic Immunology and Flow Cytometry Committee designed and implemented a new plasma cell neoplasia flow cytometry proficiency testing program-PCNEO-to allow clinical flow cytometry laboratories to monitor and assess their performance compared with a peer group. OBJECTIVE.­: To report the results from the first 4 years of the PCNEO program. DESIGN.­: Program participants were sent 2 sets of challenges per year, each including 1 wet challenge and 2 dry challenges, with associated clinical and laboratory findings. The wet challenges were composed of myeloma cell line specimens (with or without dilution in preserved whole blood) for flow cytometric analysis. The dry (paper) challenges were composed of clinical case summaries and images of flow cytometric test results from various flow cytometry laboratories of committee members. RESULTS.­: A total of 116 to 145 laboratories from 17 countries enrolled in the proficiency testing program. For the wet challenges, almost all participants (97%-100%; cumulative, 98.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of undiluted myeloma cell lines. Slightly fewer participants (89.0%-97.4%; cumulative, 95.2%) correctly identified the presence of neoplastic plasma cell populations based on flow cytometric analysis of diluted myeloma cell lines (10% or 50% dilutions into peripheral blood) intended to better represent a typical clinical sample. There was generally agreement among 80% or more of participants for positive or negative staining for CD38, CD138, CD19, CD20, and surface and cytoplasmic κ and λ light chains. Similarly, 84% to 100% of participants were able to correctly identify the presence of neoplastic plasma cell populations in paper challenges, including the presence of small, neoplastic plasma cell populations (0.01%-5.0% clonal plasma cells), or the presence of nonneoplastic plasma cell populations (correctly identified by 91%-96% of participants). CONCLUSIONS.­: Participant performance in the new proficiency testing program was excellent overall, with the vast majority of participants able to perform flow cytometric analysis and identify neoplastic plasma cell populations, and to identify small plasma cell clones or expanded populations of reactive plasma cells in dry challenge flow cytometry results. This program will allow laboratories to verify the accuracy of their testing program and test interpretations for the assessment of patients suspected of having a plasma cell neoplasm.

Reporting and Establishment of Reference Intervals for Antiphospholipid Antibody Immunoassays: A Survey of Participants in the College of American Pathologists Proficiency Testing Program.

CONTEXT.­: Misdiagnosis of antiphospholipid syndrome can occur owing to the wide diversity of antiphospholipid (aPL) assays and a lack of international calibrators and harmonized reference intervals. OBJECTIVE.­: To assess laboratory practices regarding reporting and establishing reference intervals for immunoglobulin (Ig) G/IgM anti-cardiolipin (aCL) and anti-beta-2 glycoprotein I (anti-ß2GPI) assays. DESIGN.­: Supplemental questions related to reporting and establishing reference ranges for aPL assays were sent as part of the Antiphospholipid Antibody (ACL)-B 2019 College of American Pathologists (CAP) proficiency testing survey. The response rate and methods assessment details were determined, as well as qualitative and quantitative results for 3 test samples. RESULTS.­: The number of participants reporting results for IgG aCL (n = 489), IgM aCL (n = 476), IgG anti-ß2GPI (n = 354), and IgM anti-ß2GPI (n = 331) varied by antibody type. The enzyme-linked immunosorbent assay (ELISA) (up to 58.6%, 260 of 444) was the most used method; others included multiplex (from 18.9% to 23.9%), fluorescence enzyme immunoassay (14.4%-17.6%), and chemiluminescence immunoassay (6.5%-9.0%). More respondents reported quantitative than qualitative results and manufacturer cutoff ranges were used by 92.9% and 94.2% of respondents for aCL and anti-ß2GPI, respectively. Despite variation in the use of semiquantitative ranges, qualitative negative/positive reporting of the test samples achieved almost 100% consensus. Qualitative consensus was met in contrast to the wide range of quantitative results obtained for each analyte across different kits. CONCLUSIONS.­: ELISA remains the most used method for detecting aPL antibodies with most laboratories reporting quantitative results based on manufacturers' suggested reference ranges. The categorization of quantitative results as equivocal, weak positive, or positive for responders using kits from the same manufacturer was variable.

Transposon delivery for CRISPR-based loss-of-function screen in mice identifies NF2 as a cooperating gene involved with the canonical WNT signaling molecular class of hepatocellular carcinoma.

Various molecular subclasses of hepatocellular carcinoma (HCC) exists, with many novel cooperating oncogenes and tumor suppressor genes involved in its tumorigenesis. The emerging importance of WNT signaling in HCC has been established. However, the intricate genetic mechanisms involved in this complex signaling pathway remains to be elucidated. Importantly, while some cooperating genes have been identified, there are still many unknown genes associated with catenin beta 1 (CTNNB1)-induced HCC. Mutations in both oncogenes and tumor suppressor genes are required for HCC tumorigenesis. The emergence of the CRISPR/Cas9 system has allowed researchers now to target both alleles efficiently. In this novel study, the Sleeping Beauty transposon system was used as a gene delivery system in vivo to stably integrate an expression cassette that carry pools of gRNAs and overexpress a mutant version of CTNNB1 into the hepatocyte genome. We identified 206 candidate genes that drive HCC tumorigenesis in the context of WNT signaling activation and, neurofibromin 2 (NF2) gene, a known tumor suppressor gene with clinical relevance was validated in this proof-of-principle study.

Mass Cytometry reveals unique phenotypic patterns associated with subclonal diversity and outcomes in multiple myeloma.

Multiple myeloma (MM) remains an incurable plasma cell (PC) malignancy. Although it is known that MM tumor cells display extensive intratumoral genetic heterogeneity, an integrated map of the tumor proteomic landscape has not been comprehensively evaluated. We evaluated 49 primary tumor samples from newly diagnosed or relapsed/refractory MM patients by mass cytometry (CyTOF) using 34 antibody targets to characterize the integrated landscape of single-cell cell surface and intracellular signaling proteins. We identified 13 phenotypic meta-clusters across all samples. The abundance of each phenotypic meta-cluster was compared to patient age, sex, treatment response, tumor genetic abnormalities and overall survival. Relative abundance of several of these phenotypic meta-clusters were associated with disease subtypes and clinical behavior. Increased abundance of phenotypic meta-cluster 1, characterized by elevated CD45 and reduced BCL-2 expression, was significantly associated with a favorable treatment response and improved overall survival independent of tumor genetic abnormalities or patient demographic variables. We validated this association using an unrelated gene expression dataset. This study represents the first, large-scale, single-cell protein atlas of primary MM tumors and demonstrates that subclonal protein profiling may be an important determinant of clinical behavior and outcome.

Effects of talking about side effects versus not talking about side effects on the therapeutic alliance: A controlled clinical trial.

INTRODUCTION: Side effects of psychotherapy are common. Therapists and patients must recognize negative developments to take countermeasure. Therapists can be reluctant to talk about problems of their own treatment. The hypothesis could be that talking about side effects can impair the therapeutic relationship. METHODS: We examined whether a systematic monitoring and discussion of side effects has a negative effect on therapeutic alliance. Intervention group (IG) therapists and patients filled in the UE-PT scale (unwanted events in the view of patient and therapists scale) and discussed their mutual ratings (IG, n = 20). As unwanted events can be independent of therapy, but also be treatment-related side effects, the UE-PT-scale first asks for UE and then for their relation to the ongoing treatment. In the control group (CG, n = 16) treatment was done without any special side effect monitoring. Both groups filled in the Scale for Therapeutic Alliance (STA-R). RESULTS: IG-therapists reported various unwanted events in 100% and patients in 85% of cases: complexity of problems, burdensome or overdemanding therapy, problems with work, and symptom deterioration. Any side effect was reported in 90% by therapists and in 65% by patients. Most frequent side effects were demoralization and worsening of symptoms. IG therapists observed an improvement of global therapeutic alliance in STA-R (M = 3.08 to M = 3.31, p = 0.024, interaction effect in ANOVA with two groups and measurement repetition), and reduced patient fear (M = 1.21 to M = 0.91, p = 0.012). IG patients perceived improvement in bond (M = 3.45 to M = 3.70, p = 0.045). In the CG no comparable changes were seen (alliance M = 2.97 to M = 3.00; patient fear M = 1.20 to M = 1.36; patient-perceived bond M = 3.41 to M = 3.36). CONCLUSION: The initial hypothesis must be rejected. The results suggest that monitoring, and discussion of side effects can even improve the therapeutic alliance. Therapists must not be afraid that this will endanger the therapeutic process. The use of a standardized instrument like the UE-PT-scale seems helpful.

Self- and observer ratings of capacity limitations in patients with neurological conditions.

OBJECTIVE: The purpose of this study was to compare the self- and observer ratings of capacity limitations in patients with neurological conditions. Research on this topic is relevant for assessing the patients' ability to participate in work and social life and improving collaborative patient-clinician relationships. METHOD: The self- and observer ratings of capacity limitations in a sample of N = 245 patients with neurological conditions from a rehabilitation facility were compared and assessed using the short rating of activity limitations and participation restrictions in mental disorders according to the International Classification of Functioning, Disability and Health (Mini-ICF-APP) and the equivalent self-rating questionnaire (Mini-ICF-APP-S). RESULTS: Paired-samples t-tests revealed significant differences between the self- and observer ratings for six out of 13 capacity dimensions. On average, the patients rated the capacity dimensions adherence to regulations, planning and structuring of tasks, professional competency and endurance as significantly less limited, in comparison to the observers (small to medium effect sizes). The self-ratings for limitation of contact with others and self-care were only marginally higher than the observer ratings. CONCLUSIONS: The findings show that psychological capacity limitations occur in patients with neurological conditions. In clinical practice, limitations in each capacity dimension and discrepancies in patient- and clinician-ratings should be thoroughly assessed. This is especially relevant in patients with neurological conditions who have a potential tendency to underestimate or deny their disability.

Obesity Classification of the Body Mass Index Does Not Predict Participation Restrictions at Work.

OBJECTIVE: The objective was to explore the differences of the three body mass index (BMI) obesity classes regarding sociodemographic data, medical and psychological well-being, but especially participation restrictions at work. METHODS: A specialist in psychosomatic medicine reported on the health and occupational status of 190 patients (BMI >30), who were treated as inpatients in a psychosomatic rehabilitation unit. RESULTS: Significant increases in severity or work limitations were found for higher BMI groups concerning metabolic, cardiologic, and orthopedic comorbidity. There were no differences regarding indicators of occupational participation. Independent of the obesity status, about three quarters were seen as fit for work. CONCLUSIONS: The initial hypothesis is rejected, as no difference concerning objective parameters of work participation were found between the BMI classes. The data suggest that BMI class I to BMI class III do not allow predictions of the ability to work.

Mucosa-Associated Lymphoid Tissue Lymphoma Masked as Gastric Varices With Acute Upper Gastrointestinal Bleeding: A Case Report.

Extra-nodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is uncommon and difficult to diagnose due to varied clinical presentations and endoscopic appearances masquerading as other pathology. Rarely, it has been associated with acute upper gastrointestinal (GI) bleeding. We report on a 60-year-old male who presented with an acute upper GI bleed and endoscopic findings suggestive of isolated gastric varices (GV), ultimately determined to be MALT lymphoma. Complete remission was achieved with radiation therapy, with no recurrence at a 12-month follow-up. This case highlights a unique clinical and endoscopic presentation of MALT lymphoma which providers should be aware of. We emphasize the use of endoscopic ultrasound (EUS) evaluation for accurate diagnosis.

Embitterment - Conception of a Potential Moderator to Dysfunctional and Aggressive Behaviour in Children and Adolescents.

Embitterment is an emotion which is known to everybody in reaction to injustice, humiliation, and breach of trust. Children and adolescents have an understanding of justice/injustice and fairness, violations of injustice, humiliation, and breach of trust are also stressors at a young age. In this conceptual paper it is argued that embitterment is also seen in children and adolescents, and that parents, educators and therapists should recognize this emotion. This could possibly help to early identify children at risk for severe dysfunctional and aggressive behaviours, when preventive interventions are still possible. The article concludes with concepts on how to diagnose and treat children with embitterment.

Capacity limitations in neurology patients, with and without comorbid mental disorders.

BACKGROUND: According to the International Classification of Functioning, Disability, and Health (ICF) symptoms of illness and capacity limitations must be kept apart and assessed separately. Psychological capacities are more important than physical capacities in today's world. Patients with neurological disorders not only show limitations in physical but also in psychological capacities. As in many cases there is comorbidity of neurological and mental disorders the question is to what degree this can increase psychological incapacity. METHODS: Using a cross-sectional study design, neurological patients with and without mental comorbidity were recruited in a department of neurological phase D rehabilitation. A total of 114 inpatients with both neurological and mental disorders (NM) were compared with 214 unselected patients with neurological disorders only (N). Mental comorbidity was diagnosed with the standardized "International Neuropsychiatric Interview". Capacity limitations were assessed with the "Activities and Participation in Psychological Disorders according to the International Classification of Functioning, Disability and Health" scale (Mini-ICF-APP). Qualitative reports of patients were used to validate the Mini-ICF-APP ratings. Clinical diagnoses were taken from the routine patient evaluation. RESULTS: Severe capacity limitations, which are in need of support by others, could be observed especially for endurance (NM: 73.7% vs. N: 59.8% of patients), flexibility (NM: 43.0% vs. N: 22.4%), professional competency (NM: 36.0% vs. N: 16.8%), structuring of tasks (NM: 32.5% vs. N: 15.0%). Least frequent were impairment in dyadic relationships (NM: 23.7% vs. N: 7.9%). The rank order and the qualitative descriptions of impairments were similar in both groups. CONCLUSION: Patients with neurological disorders in general show a relevant degree of capacity limitations. This is further substantially increased by mental comorbidity. Specific treatment is necessary.