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Leptomeningeal disease (LMD) is a devastating complication of cancer that is frequently underdiagnosed owing to the low sensitivity of cerebrospinal fluid (CSF) cytologic assessment, the current benchmark diagnostic method. Improving diagnostic sensitivity may lead to improved treatment decisions. To assess whether cell-free DNA (cfDNA) analysis of CSF may be used to diagnose LMD more accurately than cytologic analysis. This diagnostic study conducted in a neuro-oncology clinic at 2 large, tertiary medical centers assessed the use of genomic sequencing of CSF samples obtained from 30 patients with suspected or confirmed LMD from 2015 through 2018 to identify tumor-derived cfDNA. From the same CSF samples, cytologic analyses were conducted, and the results of the 2 tests were compared. This study consisted of 2 patient populations: 22 patients with cytologically confirmed LMD without parenchymal tumors abutting their CSF and 8 patients with parenchymal brain metastases with no evidence of LMD. Patients were considered positive for the presence of LMD if previous CSF cytologic analysis was positive for malignant cells. The analysis was conducted from 2015 to 2018. The primary outcome was the diagnostic accuracy of cfDNA analysis, defined as the number of tests that resulted in correct diagnoses out of the total number of tests assayed. Hypotheses were formed before data collection. In total, 30 patients (23 women [77%]; median age, 51 years [range, 28-81 years]), primarily presenting with metastatic solid malignant neoplasms, participated in this study. For 48 follow-up samples from patients previously diagnosed via cytologic analysis as having LMD with no parenchymal tumor abutting CSF, cfDNA findings were accurate in the assessment of LMD in 45 samples (94%; 95% CI, 83%-99%), whereas cytologic analysis was accurate in 36 samples (75%; 95% CI, 60%-86%), a significant difference (P = .02). Of 43 LMD-positive samples, CSF cfDNA analysis was sensitive to LMD in 40 samples (93%; 95% CI, 81%-99%), and cytologic analysis was sensitive to LMD in 31 samples (72%; 95% CI, 56%-85%), a significant difference (P = .02). For 3 patients with parenchymal brain metastases abutting the CSF and no suspicion of LMD, cytologic findings were negative for LMD in all 3 patients, whereas cfDNA findings were positive in all 3 patients. This diagnostic study found improved sensitivity and accuracy of cfDNA CSF testing vs cytologic assessment for diagnosing LMD with the exception of parenchymal tumors abutting CSF, suggesting improved ability to diagnosis LMD. Consideration of incorporating CSF cfDNA analysis into clinical care is warranted.

To understand the mechanisms that mediate germline genetic leukemia predisposition, we studied the inherited ribosomopathy Shwachman-Diamond syndrome (SDS), a bone marrow failure disorder with high risk of myeloid malignancies at an early age. To define the mechanistic basis of clonal hematopoiesis in SDS, we investigate somatic mutations acquired by patients with SDS followed longitudinally. Here we report that multiple independent somatic hematopoietic clones arise early in life, most commonly harboring heterozygous mutations in EIF6 or TP53 . We show that germline SBDS deficiency establishes a fitness constraint that drives selection of somatic clones via two distinct mechanisms with different clinical consequences. EIF6 inactivation mediates a compensatory pathway with limited leukemic potential by ameliorating the underlying SDS ribosome defect and enhancing clone fitness. TP53 mutations define a maladaptive pathway with enhanced leukemic potential by inactivating tumor suppressor checkpoints without correcting the ribosome defect. Subsequent development of leukemia was associated with acquisition of biallelic TP53 alterations. These results mechanistically link leukemia predisposition to germline genetic constraints on cellular fitness, and provide a rational framework for clinical surveillance strategies. Understanding the molecular basis of leukaemia predisposition is essential for intervention. The authors here investigate germline genetic leukaemia predisposition by studying Shwachman-Diamond syndrome and report compensatory inactivating mutations in EIF6 and transforming biallelic TP53 alterations.

Leptomeningeal disease (LMD) is a devastating complication of solid tumor malignancies, with dire prognosis and no effective systemic treatment options. Over the past decade, the incidence of LMD has steadily increased due to therapeutics that have extended the survival of cancer patients, highlighting the need for new interventions. To examine the efficacy of immune checkpoint inhibitors (ICI) in patients with LMD, we completed two phase II clinical trials. Here, we investigate the cellular and molecular features underpinning observed patient trajectories in these trials by applying single-cell RNA and cell-free DNA profiling to longitudinal cerebrospinal fluid (CSF) draws from enrolled patients. We recover immune and malignant cell types in the CSF, characterize cell behavior changes following ICI, and identify genomic features associated with relevant clinical phenomena. Overall, our study describes the liquid LMD tumor microenvironment prior to and following ICI treatment and demonstrates clinical utility of cell-free and single-cell genomic measurements for LMD research. Leptomeningeal disease (LMD) is a serious complication of metastatic solid tumors with a poor prognosis. Here, by using single-cell RNA sequencing of cerebrospinal fluid, the authors report genomic and immune correlates of response to immunotherapy in two cohorts of patients with LMD treated with immune checkpoint inhibitors.

The co-editors introduce a two-part Special Section of the Journal devoted to understanding and treating violence in America. They examine the relevance of clinical experience for contributions that can be made by group therapists and group dynamic thinkers to the growing national dialogue about this problem. The pervasive nature, causes, and different forms of violence in the United States are compared with those found in other countries. Underlying sociocultural values and myths, historical and current cultural contexts are considered breeding grounds for potential violence. How therapists can promote healthy change in their groups and in the broader society is explored. The articles contained in part one are reviewed against this backdrop.

The co-editors of the journal's two special issues on \"Violence in America\" from group psychotherapy and mental health standpoints review the articles in Part I and introduce the articles in Part II. The latter includes articles on anger management in groups, group psychotherapy for domestic violence, domestic \"homegrown\" terrorism, and two general commentaries. The co-editors provide broad reference points for the focus on clinical concerns, levels of treatment, variations in types of perpetrators, screening for groups, and the group-as-a-whole, relational, and social contexts of violence. Whether in small therapy groups, social interventions, or society's management of violence, empathy, boundaries, holding, and containment must be provided in such a way that they prevent violent acts while healing the hurts and shame that underlie violence in all its forms. Therapists' familiarity with these issues in their work can contribute fruitfully to treatment efforts and addressing a pressing social problem.

Several factors appear to contribute to these attitudes: many of AGPA's members are clinicians who lack familiarity with evidence-based practices and related research methods; the majority of AGPA clinicians practice some variant of longer-term psychodynamically-based group treatment which may be inherently more complicated and difficult to research than either shorterterm cognitive-behavioral treatment interventions (the group modality that has garnered the most research support) or even longer-term individual psychodynamic psychotherapy; there is a relative lack of manualized psychodynamic approaches, despite some promising efforts that are underway (e.g., Piper, Ogrodniczuk, Joyce, Weideman, & Rosie, 2007; Piper, in press); there is an absence of clear, agreed upon criteria for assessing outcome; and, until recently, with the availability of the CORE-R, there has been a lack of comprehensive, easily administered, nonintrusive, standardized assessment measures.

The beautiful evocative words of Dylan Thomas speak to the driving life force that pulses through all creation. So what, then, drives our organization, the American Group Psychotherapy Association (AGPA)? What underlying stream can we tap into to provide the energy, power, and vitality we need to go on being in a meaningful and productive fashion? And, what internal compass can we rely on to steer us in the right direction, to guide us in how we function as an organization? My purpose here is to consider how we formulate our objectives, determine our priorities, make decisions, and insure, as best we can, that we are pursuing that which is meaningful and essential, not veering drastically off course. To do this, I would like to focus briefly on the current organizational structure of AGPA, then examine the use of a strategic planning process, review our accomplishments, and lastly explore hopes and dreams for our future as the premier group psychotherapy organization in the United States.