FLT3 inhibitors potentially improve response rates in acute myeloid leukemia harboring t(6;9)(DEK::NUP214): The Mayo Clinic experience.

Not available.

Hemostatic prophylaxis and colonoscopy outcomes for patients with bleeding disorders: A retrospective cohort study and review of the literature.

INTRODUCTION: Hemostatic prophylaxis (HP) is recommended for patients with bleeding disorders (PWBD) before invasive procedures. However, evidence-based guidelines are needed to determine optimal HP strategies. AIM: To determine outcomes of HP for PWBD undergoing colonoscopy. METHODS: We undertook a retrospective cohort study of HP and outcomes of colonoscopy procedures performed between 9 November 1993 and 13 February 2018 for PWBD who received care in the Mayo Clinic Comprehensive Hemophilia Treatment Center. RESULTS: During the study period, 73 PWBD (58 with milder phenotypes: haemophilia, von Willebrand disease [subtypes 1 and 2; II, VII and XI deficiency]) underwent 141 procedures. Preprocedural HP was given to 61%, and interventions were performed in 47%. Of the 39% without preprocedural HP, postprocedural HP was given for 11%. One major (0.7%; 6 days postprocedure despite HP) and 10 minor (7%) bleeding complications occurred, which tended to be in patients with severe disease and/or after excision of larger polyps. There was no significant difference in the rate of bleeding complications with or without preprocedural HP (8.1% vs 5.5%, respectively; P = .74, Fisher's exact test). CONCLUSION: The low bleeding rates in our cohort suggest that preprocedure HP may be withheld for patients with mild bleeding disorders who undergo colonoscopy with a low likelihood of requiring an intervention or who require only low-risk intervention. This strategy may be best used in experienced centres, provided optimal local hemostasis measures are undertaken and postprocedural HP is rapidly available if high-risk intervention is required. Further studies are needed to determine optimal evidence-based HP strategies for PWBD undergoing colonoscopy.

US medical and surgical society position statements on physician-assisted suicide and euthanasia: a review.

BACKGROUND: An analysis of the position statements of secular US medical and surgical professional societies on physician-assisted suicide (PAS) and euthanasia have not been published recently. Available statements were evaluated for position, content, and sentiment. METHODS: In order to create a comprehensive list of secular medical and surgical societies, the results of a systematic search using Google were cross-referenced with a list of societies that have a seat on the American Medical Association House of Delegates. Societies with position statements were identified. These statements were divided into 5 categories: opposed to PAS and/or euthanasia, studied neutrality, supportive, acknowledgement without statement, and no statement. Linguistic analysis was performed using RapidMinder in order to determine word frequency and sentiment respective to individual statements. To ensure accuracy, only statements with word counts > 100 were analyzed. A 2-tailed independent t test was used to test for variance among sentiment scores of opposing and studied neutrality statements. RESULTS: Of 150 societies, only 12 (8%) have position statements on PAS and euthanasia: 11 for PAS (5 opposing and 4 studied neutrality) and 9 for euthanasia (6 opposing and 2 studied neutrality). Although the most popular words used in opposing and studied neutrality statements are similar, notable exceptions exist (suicide, medicine, and treatment appear frequently in opposing statements, but not in studied neutrality statements, whereas psychologists, law, and individuals appear frequently in studied neutrality statements, but not in opposing statements). Sentiment scores for opposing and studied neutrality statements do not differ (mean, 0.094 vs. 0.104; P = 0.90). CONCLUSIONS: Few US medical and surgical societies have position statements on PAS and euthanasia. Among them, opposing and studied neutrality statements share similar linguistic sentiment. Opposing and studied neutrality statements have clear differences, but share recommendations. Both opposing and studied neutrality statements cite potential risks of PAS legalization and suggest that good palliative care might diminish a patient's desire for PAS.

Postsurgical thrombotic microangiopathy: Case series and review of the literature.

OBJECTIVES: Describe the clinical presentation, treatment, and outcomes of postsurgical thrombotic microangiopathy (TMA). METHODS: In this retrospective study, records of individuals diagnosed with TMA developing within 30 days of a surgical procedure at Mayo Clinic from 2000 to 2016 were reviewed. Available literature regarding postsurgical TMA was comparatively reviewed. RESULTS: Twenty patients were diagnosed with TMA developing within 30 (median 6.5, range (1-28)) days) following a procedure. Preceding procedures included orthopedic (n = 4), vascular (n = 4), abdominal (n = 8), thoracic (n = 2), and other (n = 2). Review of the literature identified 65 patients with postsurgical TMA and cardiovascular procedures were the most common preceding surgery. The majority of patients in the current cohort and literature were treated with therapeutic plasma exchange (TPE). Among the evaluable patients in the current cohort, 100% demonstrated response to TPE; however, 25% required the addition of other therapy including eculizumab to maintain a response 80% of patients in the literature demonstrated a response to TPE. CONCLUSIONS: Although rare, early recognition and treatment of postsurgical TMA can lead to good outcomes. More research is necessary to determine the underlying pathophysiology and optimal treatment for postsurgical TMA.

Duty to speak up in the health care setting a professionalism and ethics analysis.

Staff and students working in health care settings are sometimes reluctant to speak up when they perceive patients to be at risk for harm. In this article, we describe four incidents that occurred at our institution (Mayo Clinic). In two of them, health care professionals failed to speak up, which resulted in harm; in the other two, they did speak up, which prevented harm and improved patient care. We analyzed each scenario using the Physician's Charter on Medical Professionalism and prima facie ethics principles to determine whether principles were violated or upheld. We conclude that anyone who works in a health care setting has a duty to speak up when a patient faces harm. We also provide guidance for health care institutions on promoting a culture in which speaking up is encouraged and integrated into routine practice.

Physician perspectives and compliance with patient advance directives: the role external factors play on physician decision making.

BACKGROUND: Following passage of the Patient Self Determination Act in 1990, health care institutions that receive Medicare and Medicaid funding are required to inform patients of their right to make their health care preferences known through execution of a living will and/or to appoint a surrogate-decision maker. We evaluated the impact of external factors and perceived patient preferences on physicians' decisions to honor or forgo previously established advance directives (ADs). In addition, physician views regarding legal risk, patients' ability to comprehend complexities involved with their care, and impact of medical costs related to end-of-life care decisions were explored. METHODS: Attendees of two Mayo Clinic continuing medical education courses were surveyed. Three scenarios based in part on previously court-litigated matters assessed impact of external factors and perceived patient preferences on physician compliance with patient-articulated wishes regarding resuscitation. General questions measured respondents' perception of legal risk, concerns over patient knowledge of idiosyncrasies involved with their care, and impact medical costs may have on compliance with patient preferences. Responses indicating strength of agreement or disagreement with statements were treated as ordinal data and analyzed using the Cochran Armitage trend test. RESULTS: Three hundred eighty-eight of 951 surveys were completed (41% response rate). Eighty percent reported they were likely to honor a patient's AD despite its 5 year age. Fewer than half (41%) would honor the AD of a patient in ventricular fibrillation who had expressed a desire to "pass away in peace." Few (17%) would forgo an AD following a family's request for continued resuscitative treatment. A majority (52%) considered risk of liability to be lower when maintaining someone alive against their wishes than mistakenly failing to provide resuscitative efforts. A large percentage (74%) disagreed that patients could not appreciate complexities surrounding their care while 69% agreed that costs should never impact a physician's decision as to whether to comply with a patient's AD. CONCLUSIONS: Our findings highlight the impact, albeit small, external factors have on physician AD compliance. Most respondents based their decision on the clinical situation at hand and interpretation of the patient's initial wishes and preferences expressed by the AD.

The Impact of Obesity on the Outcomes of Adult Patients with Acute Lymphoblastic Leukemia - A Single Center Retrospective Study.

INTRODUCTION: Obesity is a worldwide problem that is related to cardiac disease, thrombosis and cancer. However, little is known about the impact of obesity on the outcomes of adult acute lymphoblastic leukemia (ALL) patients. METHODS: We retrospectively evaluated a cohort of 154 newly diagnosed adult ALL patients between 1994 and 2011 at Mayo Clinic (Rochester). According to the World Health Organization (WHO) international BMI classification, patients were stratified as underweight, normal weight, overweight, and obese. For some analyses, patients were also stratified according to a two-sided non-obese or obese classification. RESULTS: The median follow-up time was 8.37 years. Obese patients were more likely to be women (p=0.024) and ≥60 years old (p=0.003). Five-year mortality rates were higher in obese patients than non-obese [HR 95% CI: 1.60 (1.03-2.50) p=0.035]. This was also the case in subgroup analysis among T-cell patients although the number of patients was small [HR 95% CI: 5.42 (1.84-15.98) p<0.001]. There was no difference in mortality among the B-cell patients. After adjusting for baseline variables, the difference in mortality remained in several models. There was no difference in EFS or cumulative incidence of relapse rates between obese and non-obese patients among the overall population. DISCUSSION: In conclusion, our study suggests that adult ALL patients with obesity have lower survival rates, especially in T-cell ALL.

Clinical Heterogeneity of the VEXAS Syndrome: A Case Series.

The objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%). The median age at VEXAS diagnosis was 74 (67, 76.5) years, and patients had a median duration of symptoms for 4 years before diagnosis. Refractory constitutional symptoms (88%), ear and nose chondritis (55%), and inflammatory arthritis (55%) were common clinical features. Vasculitis was noted in 44%. All patients had significantly elevated inflammatory markers and macrocytic anemia. Thrombocytopenia was present in 66% at diagnosis of VEXAS. Eight patients had bone marrow biopsies performed. All bone marrows were hypercellular, and there was vacuolization of the erythroid (100%) or myeloid precursors (75%). Glucocorticoids attenuated symptoms at prednisone doses ≥20 mg per day, but no other immunosuppressive agent showed consistent long-term control of disease. One patient with coexisting plasma-cell myeloma received plasma-cell-directed therapy with improvement of the inflammatory response, which is a novel finding. In conclusion, VEXAS syndrome is a clinically heterogeneous, treatment-refractory inflammatory condition caused by somatic mutation of the UBA1 gene. Patients often present with overlapping rheumatologic manifestations and persistent hematologic abnormalities. As such, internists and subspecialists, including pathologists, should be aware of this condition to avert diagnostic delay, now that the etiology of this syndrome is known.

A novel advance directives course provides a transformative learning experience for medical students.

BACKGROUND: Inadequate physician training may be a barrier to physician-patient discussions of advance directives (ADs). DESCRIPTION: The purpose of this study was to determine the effects of an ADs course, which includes completing a directive, on medical students' perceived knowledge of and preparedness for discussing ADs with patients. All 4th-year medical students completed a 10-hr bioethics course comprising interactive lecture and small-group discussion formats. Curriculum content included ethical and legal aspects of ADs. An 8-item survey with free-text entry was administered 1 month after course completion. Internal consistency reliability of survey scores was determined. Two authors independently coded the free-text comments and reached consensus on underlying themes. EVALUATION: Of the 89 students who completed the survey (response rate 80%), 87 (98%) felt more knowledgeable and 88 (99%) better equipped to counsel patients about ADs. Forty-two (47%) reported they had counseled others to complete ADs during the month after the course. Internal consistency reliability of survey scores was very good (Cronbach's alpha =.78). Dominant themes of responses to the question, "What was the most eye opening, troubling, or difficult aspect about filling out your advance directive?" included difficulties articulating wishes, legal language, selecting a surrogate, and facing mortality. CONCLUSIONS: These findings suggest an ADs course that includes completing a directive enhances medical students' empathy for and preparedness to discuss ADs with patients.

Rituximab for refractory and or relapsing thrombotic thrombocytopenic purpura related to immune-mediated severe ADAMTS13-deficiency: a report of four cases and a systematic review of the literature.

Thrombotic thrombocytopenic purpura (TTP) is a potentially life-threatening disorder that in significant proportion of cases is related to the development of autoantibodies to, and resulting severe deficiency of, the ADAMTS13 protease. However, ADAMTS13 deficiency does not account for all cases. Response to plasma exchange (PE) is seen in TTP with and without ADAMTS13 deficiency and is therefore indicated for all with a clinical diagnosis of TTP, although the pathogenesis of the latter group remains to be defined. Although the majority of cases respond to PE, a significant percent are refractory or experience relapse. Rituximab is being increasingly used off-label in this setting, but many reports do not define the pathogenesis of TTP so treated. We here report our experience with, and systematically review the published experience to date, of rituximab in management of refractory and or relapsing TTP specifically related to immune-mediated severe ADAMTS13-deficiency. In total, 73 patients met defined study inclusion criteria. The majority (approximately 95%) achieved complete remission within weeks of the first application of rituximab. The reported relapse rate was low in this patient subgroup, which carry an anticipated relapse rate of up to 60%. However, caution in interpretation of this data is needed given the relatively short median duration of follow-up of approximately 10 months. Rituximab was generally well tolerated, with few serious adverse events reported. However, three severe infectious complications were identified, including viral reactivation in keeping with black box warnings for this agent. Furthermore, reflecting the rarity of this disorder, only a relatively small number of patients have been treated and data with regards to long-term follow-up are largely based on individual case reports. Prospective studies are urgently needed to define the true efficacy and long-term safety of rituximab.

The Mayo Clinic Experience With Psychogenic Purpura (Gardner-Diamond Syndrome).

BACKGROUND: The objective of this study was to describe presentation, natural history, management and long-term outcomes of patients with psychogenic purpura (PP), also known as Gardner-Diamond Syndrome. METHODS: In this retrospective study, records of patients with a diagnosis of PP seen at Mayo Clinic, Rochester from 1976 to 2016 were reviewed. Available literature regarding PP was also comparatively reviewed. RESULTS: Seventy-six patients with a diagnosis of PP were identified and 54/76 (71%) experienced a prodromal sensation. The Condensed MCMDM-1 bleeding score, excluding cutaneous manifestations, was <3 in 91% of patients. Laboratory tests of primary and secondary hemostasis were normal. Fifty-four percent of patients had an underlying psychiatric diagnosis. Management approaches included psychological counseling and psychiatry evaluation in 44 patients. Pharmacologic treatment for 30 patients included psychotropic agents, antihistamines, hormonal medications and anti-inflammatory agents. At a median follow-up of 5years (range 1-34),13/28 (46.4%) experienced recurrent ecchymoses and 6 continued to seek hematology follow-up at Mayo Clinic, Rochester. Our data was similar to the aggregate data from case reports in the literature. CONCLUSIONS: For patients with unexplained recurrent ecchymosis a diagnosis of PP should be considered. Diagnosis is one of exclusion and initial evaluation should include documenting a bleeding score and obtaining laboratory tests assessing primary and secondary hemostasis. The relatively low bleeding scores together with laboratory assessments support that PP is primarily a dermal rather than a systemic bleeding diathesis. In our cohort, addressing psychological stressors was the most effective treatment; however pharmacologic therapy can be used for refractory disease.

3023 Mayo Clinic Patients With Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups.

OBJECTIVE: To document the Mayo Clinic decades-long experience with myeloproliferative neoplasms (MPNs) and provide mature risk-stratified survival data and disease complication estimates. PATIENTS AND METHODS: All Mayo Clinic patients with World Health Organization-defined MPNs constituted the core study group and included those with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). RESULTS: A total of 3023 consecutive patients (median age, 62 years; range, 18-96 years) were considered: 665 PV, 1076 ET, and 1282 PMF. From October 27, 1967, through December 29, 2017, 1631 deaths (54%), 183 leukemic transformations (6%), 244 fibrotic progressions (14%), and 516 thrombotic events (17%) were recorded. Median overall survival (OS) was 18 years for ET, 15 years for PV, and 4.4 years for PMF (P<.05 for all intergroup comparisons). Inferior survival was documented in patients with ET diagnosed more recently (post-1990) (P<.001), whereas survival data were time independent in PV and PMF. After conventional risk stratification, OS in low-risk ET and low-risk PV were superimposed (P=.89) but each differed significantly from that of age- and sex-matched controls (P<.001). Leukemia-free survival was similar for ET and PV (P=.22) and significantly worse with PMF (P<.001). Compared with ET, PV was associated with higher risk of fibrotic progression (P<.001). Thrombosis risk after diagnosis was highest in PV and lowest in PMF (P=.002 for PV vs ET; P=.56 for ET vs PMF; and P=.001 for PV vs PMF). CONCLUSION: This study provides the most mature survival and outcomes data in MPNs and highlights MPN subgroup risk categorization as key in appraising disease natural history. The OS was only marginally better in ET compared with PV, and PV displayed a higher risk of thrombosis and fibrotic progression.