Perceived Educational Needs of Substance Use Peer Support Specialists: A Qualitative Study.

The opioid crisis is an ever-growing issue nationwide. The role of peer support specialists has received widespread acceptance in the substance use and behavioral health spheres. However, there is a lack of standardization on the training required for peer support specialists to function as competent members of integrated behavioral health teams. We conducted qualitative focus groups with 14 practicing certified peer support specialists to determine their perceived educational needs. Inductive thematic analysis was used to analyze the data and six themes emerged: mental health and suicide prevention training, diversity, equity, and inclusion training, counseling skills training, family systems approach to care training, professionalism training, and taking care of self - mind, soul, and body training. To improve peer support specialists' confidence in their ability to competently perform their jobs, important topics need to be incorporated into their educational training and preparation.

Comparability of MMPI-3 scores from remote and in-person administrations and the impact of the COVID-19 pandemic on MMPI-3 scores.

The COVID-19 pandemic onset necessitated remote administration of psychological instruments, including the Minnesota Multiphasic Personality Inventory-3 (MMPI-3). Although previous evidence has demonstrated that MMPI scale scores are robust across administration modalities, the specific effects of remote administration on the psychometric properties of MMPI-3 scale scores must be investigated. Distinguishing psychometric differences due to administration modality from substantive changes in psychological symptoms due to the COVID-19 pandemic is also important. Thus, goals of the present study include evaluating the psychometric comparability of MMPI-3 scores derived from in-person and remote administration modalities and examining substantive scale scores changes associated with the COVID-19 pandemic. Using a large sample of college students (n = 2,503), rates of protocol invalidity, mean scale scores, reliability, and criterion validity were compared across participants completing the MMPI-3 in-person (both prior to and after the onset of COVID-19) and via remote administration. Results demonstrate comparably low rates of protocol invalidity, negligible differences in reliability, and similar patterns of criterion validity for MMPI-3 scale scores across administration modalities. Results also indicate that mean MMPI-3 scale scores pre- and post-COVID-19 onset substantially differ on select scales, but that scores on remote and in-person protocols administered post-COVID-19 have negligible differences. Remote MMPI-3 scale scores also demonstrated expected patterns of correlations with external criteria, supporting the validity of remote scores. Overall, the present study demonstrates that MMPI-3 protocols administered remotely and in-person are extremely psychometrically similar, although scores have generally increased post-COVID-19 onset for reasons independent of administration modality. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Pericardial Effusion Causing Cardiac Tamponade in a 10-Year-Old Male.

A 10-year-old male with a past medical history of premature pubarche, mild persistent asthma, and eczema presented to the emergency department with progressive dyspnea and chest pain. On examination, he was found to be tachycardic and tachypneic. Chest radiograph demonstrated cardiomegaly, bilateral pleural effusions, and scattered atelectasis. Echocardiogram revealed a large pericardial effusion with right atrial collapse. The patient was admitted to the pediatric ICU for pericardiocentesis and drain placement. As he later became hypertensive and febrile, we will discuss how our patient's hospital course guided our differential diagnosis and how we arrived at a definitive diagnosis using a multidisciplinary approach.

Genome-wide CRISPR-Cas9 screen reveals a persistent null-hyphal phenotype that maintains high carotenoid production in Yarrowia lipolytica.

Yarrowia lipolytica is a metabolic engineering host of growing industrial interest due to its ability to metabolize hydrocarbons, fatty acids, glycerol, and other renewable carbon sources. This dimorphic yeast undergoes a stress-induced transition to a multicellular hyphal state, which can negatively impact biosynthetic activity, reduce oxygen and nutrient mass transfer in cell cultures, and increase culture viscosity. Identifying mutations that prevent the formation of hyphae would help alleviate the bioprocess challenges that they create. To this end, we conducted a genome-wide CRISPR screen to identify genetic knockouts that prevent the transition to hyphal morphology. The screen identified five mutants with a null-hyphal phenotype-ΔRAS2, ΔRHO5, ΔSFL1, ΔSNF2, and ΔPAXIP1. Of these hits, only ΔRAS2 suppressed hyphal formation in an engineered lycopene production strain over a multiday culture. The RAS2 knockout was also the only genetic disruption characterized that did not affect lycopene production, producing more than 5 mg L-1 OD-1 from a heterologous pathway with enhanced carbon flux through the mevalonate pathway. These data suggest that a ΔRAS2 mutant of Y. lipolytica could prove useful in engineering a metabolic engineering host of the production of carotenoids and other biochemicals.

Examining the Psychometric Equivalency of MMPI-3 Scale Scores Derived From the MMPI-3 and the MMPI-2-RF-EX.

The current study evaluated the comparability of Minnesota Multiphasic Personality Inventory-3 (MMPI-3) scale scores derived from the 335-item MMPI-3 to MMPI-3 scale scores derived from the 433-item MMPI-2 restructured form-expanded version (MMPI-2-RF-EX), an enhanced version of the MMPI-2-RF that was used to develop and validate the MMPI-3. To that end, we examined data from 192 college undergraduates who completed both the MMPI-3 and MMPI-2-RF-EX 1 week apart using a counterbalanced design. Across versions, mean T-scores and standard deviations, estimates of internal consistency, and standard error of measurement values, were highly similar, indicating no clinically meaningful differences across versions. We also compared between-version test-retest comparability values with within-version values calculated using a sample of undergraduates (N = 318) who completed the MMPI-2-RF-EX twice over the same time interval, finding only marginal differences across the two samples. Finally, we computed column-vector correlations between MMPI-3 scores from both versions and several criterion measures, where results reflected no effect of test version on external validity. Overall, we determined that scale scores derived from either booklet are psychometrically interchangeable, indicating that MMPI-3 scale scores obtained from an administration of the MMPI-2-RF-EX can be applied when using the 335-item MMPI-3.

Fibrin-Associated Diffuse Large B Cell Lymphoma Found on Revision Arthroplasty of the Knee.

Fibrin-associated diffuse large B cell lymphoma (FA-DLBCL) is a rare Epstein-Barr viruspositive B cell lymphoma that is nonmass-forming, does not directly produce symptoms, and is incidentally discovered on histological examination of tissues excised for other reasons. Despite overlap in morphologic and immunophenotypic features with aggressive B cell neoplasms, FA-DLBCL shows an excellent clinical outcome, even with surgical excision alone. We report an extremely rare occurrence of FA-DLBCL found in association with a metallic implant on revision arthroplasty of the knee. This report also illustrates the need for an integrated multidisciplinary approach for accurate diagnosis and avoidance of overtreatment.

Summix: A method for detecting and adjusting for population structure in genetic summary data.

Publicly available genetic summary data have high utility in research and the clinic, including prioritizing putative causal variants, polygenic scoring, and leveraging common controls. However, summarizing individual-level data can mask population structure, resulting in confounding, reduced power, and incorrect prioritization of putative causal variants. This limits the utility of publicly available data, especially for understudied or admixed populations where additional research and resources are most needed. Although several methods exist to estimate ancestry in individual-level data, methods to estimate ancestry proportions in summary data are lacking. Here, we present Summix, a method to efficiently deconvolute ancestry and provide ancestry-adjusted allele frequencies (AFs) from summary data. Using continental reference ancestry, African (AFR), non-Finnish European (EUR), East Asian (EAS), Indigenous American (IAM), South Asian (SAS), we obtain accurate and precise estimates (within 0.1%) for all simulation scenarios. We apply Summix to gnomAD v.2.1 exome and genome groups and subgroups, finding heterogeneous continental ancestry for several groups, including African/African American (∼84% AFR, ∼14% EUR) and American/Latinx (∼4% AFR, ∼5% EAS, ∼43% EUR, ∼46% IAM). Compared to the unadjusted gnomAD AFs, Summix's ancestry-adjusted AFs more closely match respective African and Latinx reference samples. Even on modern, dense panels of summary statistics, Summix yields results in seconds, allowing for estimation of confidence intervals via block bootstrap. Given an accompanying R package, Summix increases the utility and equity of public genetic resources, empowering novel research opportunities.

Ethics and governance for internet-based conservation science research.

Internet-based research is increasingly important for conservation science and has wide-ranging applications and contexts, including culturomics, illegal wildlife trade, and citizen science. However, online research methods pose a range of ethical and legal challenges. Online data may be protected by copyright, database rights, or contract law. Privacy rights may also restrict the use and access of data, as well as ethical requirements from institutions. Online data have real-world meaning, and the ethical treatment of individuals and communities must not be marginalized when conducting internet-based research. As ethics frameworks originally developed for biomedical applications are inadequate for these methods, we propose that research activities involving the analysis of preexisting online data be treated analogous to offline social science methods, in particular, nondeceptive covert observation. By treating internet users and their data with respect and due consideration, conservationists can uphold the public trust needed to effectively address real-world issues.

Ética y Gestión para la Investigación Científica de la Conservación Basada en Internet Resumen La investigación basada en internet es cada vez más importante para las ciencias de la conservación, además de tener contextos y aplicaciones de gran alcance como el análisis de textos, el mercado ilegal de fauna y la ciencia ciudadana. Sin embargo, los métodos de investigación en línea representan una gama de retos éticos y legales pues los datos virtuales pueden estar protegidos por derechos de autor, derechos de base de datos o leyes contractuales. Además, los derechos de privacidad pueden restringir el uso y el acceso a los datos, así como también los requerimientos éticos impuestos por las instituciones. Los datos virtuales tienen valor en el mundo real y el tratamiento ético de los individuos y de las comunidades no se debe marginalizar cuando se realiza una investigación por internet. Ya que los marcos éticos desarrollados originalmente para aplicarse en temas biomédicos son inadecuados para estos métodos, proponemos que las actividades de investigación que involucran el análisis de los datos virtuales preexistentes sean tratadas como análogas a los métodos no virtuales de las ciencias sociales, especialmente la observación encubierta no engañosa. Si se trata a los usuarios del internet y a sus datos con respeto y la consideración debida, los conservacionistas pueden mantener la confianza pública necesaria para tratar efectivamente los asuntos del mundo real.

Associations Between MMPI-2-RF Internalizing RC Scales and Positive Characteristics.

Past studies indicate that the low scores on the MMPI and MMPI-2 Clinical and Content Scales can reflect positive characteristics. It is currently unclear, however, whether scales on the MMPI-2-Restructured Form (MMPI-2-RF) have that ability. Accordingly, we examined whether low scores on Restructured Clinical (RC) Scales assessing internalizing difficulties (i.e., RCd, RC2, and RC7) can reflect self-esteem, life satisfaction, positive and negative affect, and optimism. When considering the full range of scores, each of the internalizing RC Scales demonstrated the expected pattern of associations with these characteristics. Across difference and percentage bend analyses, however, only RC2 had significant associations-namely, with positive affect, self-esteem, and life satisfaction. This study corroborates that high scores on the internalizing RC scales have interpretations consistent with past literature, but also uniquely suggests that below average RC2 scores may reflect increased positive affect, self-esteem, optimism, and satisfaction with life.

Correction to: Comparative multidimensional molecular analyses of pediatric diffuse intrinsic pontine glioma reveals distinct molecular subtypes.

The original version of this article unfortunately contained a mistake.

Surgical Pathology "Boot Camp": A Military Experience.

CONTEXT.­: A common concern in pathology residency training is the variability with which incoming trainees have attained basic pathology competencies during undergraduate medical education. While multifactorial deficiencies are likely due to recent de-emphasis of dedicated pathology courses during preclinical training, accelerating the transition from medical student to pathology resident is critical-particularly in military practice where a greater degree of autonomy is required of recent graduates. OBJECTIVE.­: To describe the implementation and results of a 4-week surgical pathology "boot camp" in the largest military pathology residency program in the United States. DESIGN.­: Interns were administered an assessment on basic pathology knowledge, slide practicals, and a skills self-assessment. All specimens were grossed by interns with constant direct supervision. A daily microscopic didactic session was given by an upper level resident and a daily gross conference was led by the interns. Subsequent academic performance was evaluated via monthly slide practicals and diagnostic agreement with faculty. RESULTS.­: Following boot camp, average scores on the knowledge assessment increased from 36.0% ± 16.2% (standard deviation [SD]) to 80.0% ± 12.6% (SD) (P < .001). Slide practical scores showed an increase from 32% ± 12.0% (SD) to 74.0% ± 16.2% (SD) (P < .001). Skills self-assessment showed a global increase across all measures. Throughout the following academic year, postgraduate year 1 (PGY1) residents performed at the same level of current PGY2 residents, based on surgical pathology faculty diagnostic agreement and slide practical performance. CONCLUSIONS.­: An intense 4-week surgical pathology rotation specifically tailored to incoming interns was successful in transitioning medical students to pathology residents within a relatively short time.

The Utility of Phosphohistone H3 (PHH3) in Follicular Lymphoma Grading: A Comparative Study With Ki-67 and H&E Mitotic Count.

OBJECTIVES: To determine the utility of phosphohistone H3 (PHH3) mitotic count (MC) in grading follicular lymphoma (FL). METHODS: FL cases were identified (2005-2017). Three hematopathologists recorded their average Ki-67 proliferation index, MC/high-power field (hpf) using PHH3 and H&E stains, and number of centroblasts/hpf. Results were assessed for correlations and interobserver variability. RESULTS: Forty-three cases of FL were studied. PHH3 MC resulted in the strongest correlation to grade (r = 0.701, P < .0001) compared with Ki-67 proliferation index (PI) (r = 0.681, P < .0001) and H&E MC (r = 0.536, P = .0002) and the strongest linear relationship to centroblast count (R2 = 0.453). Agreement among pathologists was strongest for PHH3 (intraclass correlation coefficient [ICC] = 0.86) followed by Ki-67 PI (ICC = 0.85) and H&E MC (ICC = 0.78). CONCLUSIONS: PHH3 correlates best to histologic grade and has less interobserver variability compared with Ki-67 PI and H&E MC. These results support using PHH3 as an adjunct in FL grading.

Clinicopathologic Features and Clinical Outcome Differences in De Novo Versus Secondary Histiocytic Sarcomas: A Multi-institutional Experience and Review of the Literature.

INTRODUCTION: Histiocytic sarcoma (HS) is a rare malignant neoplasm that can occur in patients with a history of treatment for hematologic or solid tumors. Because no optimal treatment has been defined and standardized, the treatment modalities used and outcomes reported have been highly variable. In the present study, 3 major institutions explored the clinicopathologic features of de novo and secondary HS. MATERIALS AND METHODS: After institutional review board approval, clinical, histopathologic, and immunophenotypic data were collected from patients with a diagnosis of HS and treated at the University of Alabama at Birmingham, University of New Mexico, or Brooke Army Medical Center from January 1, 2003 to December 31, 2016. RESULTS: The databases revealed 23 unique cases of HS. The mean age was 55.4 years (range, 5-84 years) and the male-to-female ratio was 0.92. The mean follow-up period was 89.82 months (range, 14-172 months). Of the 23 patients with HS, 6 had a history of an unrelated malignancy treated with chemotherapy or radiotherapy, with a mean delay of 42.2 months (range, 12-91 months). The mean overall survival during the study period was 54.1 months. The overall survival of those with de novo HS was 70 months compared with 11.8 months for those with secondary HS, with a mean difference of 58.2 months (95% confidence interval, 26.2-90.2 months; P = .001). CONCLUSION: The shorter overall survival with secondary HS suggests a more aggressive course than that with de novo disease. Larger scale studies are needed to further investigate the biology and genetics of HS.

Using a Validated Middle-Age and Geriatric Risk Tool to Identify Early (<48 Hours) Hospital Mortality and Associated Cost of Care.

OBJECTIVES: (1) To demonstrate that a validated trauma triage score for middle-aged and geriatric patients could identify those at high risk of mortality within the first 2 days of hospitalization and (2) determine the cost of care for this cohort of patients. DESIGN: Prospective cohort study. SETTING: Single level 1 trauma center. PATIENTS: Patients 55 years of age and older who were evaluated in the emergency department setting by orthopaedics or who met the American College of Surgeons Tier 1-3 criteria. INTERVENTION: Calculation of validated trauma triage score, Score for Trauma Triage in Geriatric and Middle-aged patients, using patient's demographic, injury severity, and functional status; main outcome measurements: length of stay, inpatient mortality, time between presentation and time of death, and direct variable costs of hospitalization. RESULTS: A total of 1470 consecutive patients (mean age of 72.2 ± 11.9 years) were enrolled in this study, 17 of whom died within 48 hours of presentation to the emergency department. These patients had a significantly higher trauma triage score than the rest of the cohort with a score of 50.9% ± 37.2% versus 3.3% ± 9.5%, P < 0.001 indicating that they had a mean risk of inpatient mortality of over 50%. Mean total cost per day was much higher in the cohort of patients who died within 48 hours of admission compared with all other trauma patients [$49,367 ± $79,057 vs. $3966 ± $2897 (P = 0.031)]. CONCLUSIONS: To achieve value-based care in this high-risk cohort, targeted cost savings while improving patient outcomes and/or expediting goals-of-care and end-of-life goals is necessary and the STTGMA score allows for stratification of these patients in both mortality risk and cost profile.

A Case of Spontaneously Improving Secondary Hemophagocytic Lymphohistiocytosis in an Adult Associated with T-Cell Histiocyte-Rich Large B-Cell Lymphoma.

Secondary hemophagocytic lymphohistiocytosis (HLH) in adults is a rare, often fatal syndrome characterized by widespread immune dysregulation. It is seen as a complication of infections, autoimmune diseases, and malignancies. Among the malignancy-related causes, aggressive T-cell or NK-cell neoplasms are most notable, while B-cell lymphomas are less commonly implicated. We present the case of a 32-year-old male transferred to our facility with concern for HLH. During the first week of his hospitalization, his diagnosis was confirmed and the patient demonstrated spontaneous improvement in his symptoms prompting us to delay therapy while searching for a primary cause. In the second week, the patient deteriorated, leading us to initiate steroid monotherapy in the absence of a cause for his HLH. Meanwhile, pathology results from an excisional lymph node biopsy confirmed a diagnosis of T-cell/histiocyte-rich large B-cell lymphoma (TCHRLBCL). Subsequently, we initiated therapy with dose-adjusted R-EPOCH. The patient achieved a complete remission of both HLH and TCHRLBCL as well as a complete return to his prior functional status. In our review of the literature, this represents only the second documented case of HLH associated with TCHRLBCL and the only documented case of an adult experiencing significant spontaneous recovery in this context.

Primary management of atypical meningioma: treatment patterns and survival outcomes by patient age.

PURPOSE: The initial management of atypical meningiomas poses a distinct clinical challenge in that treatment protocols have not been fully established, and outcomes, especially differences by patient age, have not been broadly measured. The National Cancer Database (NCDB) allows for analysis of a large, diverse patient population to determine clinical parameters and survival outcomes based on the initial treatment of patients with atypical meningiomas. METHODS: Analysis of the NCDB yielded 3611 atypical meningioma patients treated between 2008 and 2012. Principal treatment paradigms included surgery with or without radiation. Survival estimates were calculated using Kaplan-Meier curves stratified by age at diagnosis for each treatment paradigm. Subset analysis was performed for socio-economic factors. RESULTS: Overall 5-year survival rate was 77.6% and declined with increasing patient age (p < 0.0001). Five-year survival for patients ≤ 45 years undergoing surgery alone was 89.3 vs. 44.4% for those > 75 years (p < 0.0001). For patients undergoing surgery with adjuvant radiation, 5-year survival was 93.7% in those ≤ 45 years and 54.1% in those > 75 years (p < 0.0001). Use of adjuvant radiation was stable over time. Private-insured patients were more likely to receive adjuvant radiation (p = 0.0001). CONCLUSIONS: Patients treated for atypical meningioma have high rates of 5-year survival. A marginal survival benefit of adjuvant radiation was observed for patients < 55 and > 75 years, while patients between 55 and 75 years tended to have slightly improved survival with surgery alone. Though surgery remains the standard of care in the primary treatment of atypical meningioma, the decision to administer radiation post-operatively has remained controversial.

The relationship between physical activity and vitamin D status in postpartum lactating and formula-feeding women.

Existing research shows an association between physical activity levels and vitamin D status in the elderly, men, women, children, and adolescent populations. This association has not yet been investigated in postpartum women. We hypothesized that based on the relationship between vitamin D and physical activity found in other populations, greater physical activity levels in postpartum women will be associated with higher serum 25(OH)D levels. A post hoc analysis of 286 postpartum women with self reported physical activity data from the America on the Move survey, and measured circulating serum 25(OH)D (measured by RIA) as an indicator of vitamin D status, was gathered at baseline (4-6 weeks postpartum), 4 months, and 7 months postpartum. The data were analyzed using SAS 9.4 (Cary, NC). 39.9% of women at visit 1 (baseline), 52.8% of women at visit 4 (month 4), and 55.9% of women at visit 7 (month 7) were meeting the NIH recommendation of 150min of moderate intensity (3-6 METs) physical activity per week. Significant differences were seen in physical activity by race (p=0.007). Caucasians were more likely to meet the standard recommendation than African Americans or Hispanics. Using multiple regression models to examine associations between duration of physical activity and 25(OH)D concentration, controlling for race, BMI, feeding type, and METs, it was found that at visit 1, an increase in physical activity was associated with an increase in 25(OH)D of 1.3nmol/L (p=0.03) and achieving at least 2.5h/wk of physical activity had a trending association with an increase in 25(OH)D of 7.23nmol/L (p=.05). At visit 4 (also controlling for treatment group and sun exposure) achieving at least 1.5h/wk of physical activity was associated with an increase in 25(OH)D of 11.73nmol/L (p=.04). By visit 7, no association between physical activity and maternal 25(OH)D was observed. In a repeated measures, mixed model analysis predicting maternal 25(OH)D during the study, achieving at least the recommended 150min per week of physical activity (>2.5h) was not significantly associated with vitamin D status (pNS). While no definitive conclusions can be drawn regarding precise levels of physical activity influencing 25(OH)D levels in postpartum women, the data suggest that increased activity during the first 4 months after birth is associated with improved vitamin D status. Additional research is needed because of the inconsistency seen at visit 7.

Aleukemic Myeloid Leukemia Cutis with a Kikuchi Disease-Like Inflammatory Pattern in Myelodysplastic Syndrome.

Myeloid leukemia cutis (MLC) is a rare disease characterized by the infiltration of neoplastic myeloid, myelomonocytic, or monocytic precursors into the skin, producing clinically nonspecific-appearing papules, nodules, plaques, or purpura that necessitate biopsy for definitive diagnosis. In general, it is considered an extramedullary manifestation of acute myeloid leukemia (AML) similar to myeloid sarcoma, also known as a chloroma. MLC often develops in patients with an established diagnosis of AML and is only rarely seen before the onset of systemic disease. Even more rarely, some patients are found to have an underlying nonleukemic bone marrow disease, such as a myelodysplastic syndrome (MDS). It is in these latter settings that the somewhat perplexing terminology aleukemic leukemia cutis (ALC) has been used widely. As may be imagined, establishing a diagnosis of ALC can be problematic and typically requires a high index of suspicion with careful integration of clinical, histopathological, and laboratory data. Once a diagnosis of ALC is made, a complete hematologic workup, including assessment of the patient's bone marrow, is essential because a diagnosis of MLC (with or without systemic leukemia) generally indicates a poor prognosis. When discovered in a patient with MDS, MLC has been suggested to herald progression toward more advanced disease. We present a rare case of so-called aleukemic myeloid leukemia cutis in an 82-year-old man subsequently diagnosed as having MDS without progression to overt AML. This case also illustrates a seemingly rare Kikuchi disease-like inflammatory pattern that obscured the underlying leukemic infiltrate in the skin, delaying its recognition.

Hemophagocytosis-Related (Asian Variant) Intravascular Large B-Cell Lymphoma in a Hispanic Patient: A Case Report Highlighting a Micronodular Pattern in the Spleen.

OBJECTIVES: We report a case of hemophagocytosis-related (Asian variant) intravascular large B-cell lymphoma (IVLBCL) in a patient of Western origin initially diagnosed by splenectomy with diffuse large B-cell lymphoma (DLBCL) with a micronodular pattern. The clonal relationship between these two DLBCL subtypes is also investigated. METHODS: Hemophagocytosis-related (Asian variant) IVLBCL was identified at autopsy in a 62-year-old Hispanic woman, in North America, following an antemortem diagnosis of massive splenic involvement by DLBCL with a micronodular pattern, a feature not expected of IVLBCL. RESULTS: These two apparently distinct lymphoma types demonstrated similar immunophenotypic profiles and IgH gene rearrangements of identical size suggesting a clonal relationship. The 2008 WHO classification system describes IVLBCL in the spleen as having a sinusoidal pattern. CONCLUSIONS: Our observations provide the first molecular genetic support for a seemingly underrecognized micronodular pattern of IVLBCL in the spleen and further support the proposal of a "mixed variant" of IVLBCL with concomitant "intravascular" and "solid" phases of disease.