Glial dysregulation in the human brain in fragile X-associated tremor/ataxia syndrome.

Short trinucleotide expansions at the FMR1 locus are associated with the late-onset condition fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and pathological features from fragile X syndrome (associated with longer expansions), with no clear molecular explanation for these marked differences. One prevailing theory posits that the shorter, premutation expansion uniquely causes extreme neurotoxic increases in FMR1 mRNA (i.e., four to eightfold increases), but evidence to support this hypothesis is largely derived from analysis of peripheral blood. We applied single-nucleus RNA sequencing to postmortem frontal cortex and cerebellum from 7 individuals with premutation and matched controls (n = 6) to assess cell type-specific molecular neuropathology. We found only modest upregulation (~1.3-fold) of FMR1 in some glial populations associated with premutation expansions. In premutation cases, we also identified decreased astrocyte proportions in the cortex. Differential expression and gene ontology analysis demonstrated altered neuroregulatory roles of glia. Using network analyses, we identified cell type-specific and region-specific patterns of FMR1 protein target gene dysregulation unique to premutation cases, with notable network dysregulation in the cortical oligodendrocyte lineage. We used pseudotime trajectory analysis to determine how oligodendrocyte development was altered and identified differences in early gene expression in oligodendrocyte trajectories in premutation cases specifically, implicating early cortical glial developmental perturbations. These findings challenge dogma regarding extremely elevated FMR1 increases in FXTAS and implicate glial dysregulation as a critical facet of premutation pathophysiology, representing potential unique therapeutic targets directly derived from the human condition.

Spike ripples localize the epileptogenic zone best: an international intracranial study.

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone compared with other leading interictal biomarkers in a multicentre, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centres who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection [International League Against Epilepsy Class 1 outcome (ILAE 1)] and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz) and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. Overall, 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001 and P < 0.001, respectively). Among ILAE 1 subjects, the mean spike ripple rate was higher in the resected volume (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared with ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01) or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicentre cohort, when surgical resection was successful, the majority of spike ripples were removed. Furthermore, automatically detected spike ripples localize the epileptogenic tissue better than spikes, spike-gamma, wideband HFOs, ripples and fast ripples.

Myeloid neoplasm with histiocytosis and spleen tyrosine kinase fusion responds to fostamatinib.

Not available.

Innovation and Missed Opportunities in Internal Medicine Undergraduate Education During COVID-19: Results from a National Survey.

BACKGROUND: COVID-19 disrupted undergraduate clinical education when medical schools removed students from clinical rotations following AAMC recommendations. Clerkship directors (CDs) had to adapt rapidly and modify clerkship curricula. However, the scope and effects of these modifications are unknown. OBJECTIVE: To examine the effects of the initial phase of COVID-19 on the internal medicine (IM) undergraduate clinical education. DESIGN: A nationally representative web survey. PARTICIPANTS: IM CDs from 137 LCME-accredited US medical schools in 2020. MAIN MEASURES: Items (80) assessed clerkship structure and curriculum, assessment in clerkships, post-clerkship IM clinical experiences, and CD roles and support. The framework of Understanding Crisis Response (Royal Society for Encouragement of Arts, Manufactures, and Commerce) was used to determine whether curricular modifications were "amplified," "restarted," "let go," or "ended." KEY RESULTS: Response rate was 74%. In response to COVID-19, 32% (32/101) of clerkships suspended all clinical activities and 66% (67/101) only in-person. Prior to clinical disruption, students spent a median of 8.0 weeks (IQR: 2) on inpatient and 2.0 weeks (IQR: 4) on ambulatory rotations; during clinical re-entry, students were spending 5.0 (IQR: 3) and 1.0 (IQR: 2) weeks, respectively. Bedside teaching and physical exam instruction were "let go" during the early phase. Students were removed from direct patient care for a median of 85.5 days. The sub-internship curriculum remained largely unaffected. Before the pandemic, 11% of schools were using a pass/fail grading system; at clinical re-entry 47% and during the survey period 23% were using it. Due to the pandemic, 78.2% of CDs assumed new roles or had expanded responsibilities; 51% reported decreased scholarly productivity. CONCLUSIONS: Curricular adaptations occurred in IM clerkships across US medical schools as a result of COVID-19. More research is needed to explore the long-term implications of these changes on medical student education and clinical learning environments.

Roles and Responsibilities of Medicine Subinternship Directors : Medicine Subinternship Director Roles.

BACKGROUND: The internal medicine (IM) subinternship (also referred to as acting internship) plays a crucial part in preparing medical students for residency. The roles, responsibilities, and support provided to subinternship directors have not been described. OBJECTIVE: We sought to describe the current role of IM subinternship directors with respect to their responsibilities, salary support, and reporting structure. DESIGN: Nationally representative, annually recurring thematic survey of IM core clerkship directors with membership in an academic professional association as of September 2017. PARTICIPANTS: A total of 129 core clinical medicine clerkship directors at Liaison Committee on Medical Education fully accredited U.S./U.S.-territory-based medical schools. MAIN MEASURES: Responsibilities, salary support, and reporting structure of subinternship directors. KEY RESULTS: The survey response rate was 83.0% (107/129 medical schools). Fifty-one percent (54/107) of respondents reported overseeing both core clerkship inpatient experiences and/or one or more subinternships. For oversight, 49.1% (28/53) of subinternship directors also reported that they were the clerkship director, 26.4% (14/53) that another faculty member directed all medicine subinternships, and 18.9% (10/53) that each subinternship had its own director. The most frequently reported responsibilities for the subinternship directors were administration, including scheduling, and logistics of student schedules (83.0%, 44/53), course evaluation (81.1%, 43/53), and setting grades 79.2% (42/53). The modal response for estimated FTE per course was 10-20% FTE, with 33.3% (16/48) reporting this level of support and 29.2% (14/54) reporting no FTE support. CONCLUSIONS: The role of the IM subinternship director has become increasingly complex. Since the IM subinternship is critical to preparing students for residency, IM subinternship directors require standard expectations and adequate support. Future studies are needed to determine the appropriate level of support for subinternship directors and to define essential roles and responsibilities.

Trauma care in older people: charting a path from outlier to excellence.

Trauma in older people leads to substantial morbidity and mortality. The National Hip Fracture Database (NHFD) has driven improved practice with units compared to identify outliers. In 2013, our unit was an outlier for mortality post hip fracture (30-day mortality 12.2% vs. 8.3% nationally). This triggered external review. In 2019 the unit was highlighted as an exemplar in the UK. We describe the process that moved us from outlier to outstanding. After the initial review process, we made changes to our healthcare system, with regular reassessment of progress and care quality. Examples include a dedicated hip fracture unit, strong leadership (Nursing, Orthopaedic, Geriatrician, Anaesthetic), consultant-led in-depth monthly mortality reviews, changes to admission pathways and delirium prevention. Improvements were seen in all aspects of hip fracture care in 2019 compared with 2012. Thirty-day case-mixed adjusted mortality halved (12.2-6.1%), with substantial reductions in reoperations and pressure sores. Length of stay reduced by 5.9 days. In 2019 our unit's performance was significantly above the national average for all six indicators assessed by NHFD: prompt orthogeriatric review (97% vs. 91% national average), prompt surgery (85% vs. 68%); NICE compliant surgery (85% vs. 74%); prompt mobilisation (93% vs. 81%); not delirious postoperatively (77% vs. 69%); return to original residence (78% vs. 71%). The NHFD highlighted our Unit as one of nine (from 175 total) highly performing UK trusts. We summarise our service development and improvement work undertaken to achieve 'outstanding' status, which provides a valuable template to units managing trauma in older people.

Finding relief for the self-conscious esophagus: laparoscopic anti-reflux surgery and the esophageal hypersensitivity and anxiety scale.

INTRODUCTION: Measures of mood and effective coping strategies have notable correlations with quality of life and treatment responses. There is evidence that patients with previously diagnosed anxiety disorders have less improvement in patient-reported outcome measures (PROMs) after laparoscopic anti-reflux surgery (LARS) and that objective pathology does not correlate well with symptom severity. We were interested in investigating whether anxiety and hypervigilance, as measured preoperatively with the esophageal hypervigilance anxiety scale (EHAS), is associated with the improvement in GERD-specific PROMs and EHAS scores 6 months after LARS. METHODS: We performed a retrospective cohort study of 102 adult patients (31% men, average age 64) who underwent LARS. In the preoperative evaluation, baseline gastroesophageal reflux disease-health-related quality of life (GERD-HRQL), laryngopharyngeal reflux symptom index (LPR-RSI) and EHAS scores were collected in addition to the standard reflux workup, including endoscopy, manometry, barium swallow, and pH study. For all three surveys, a higher score represents worse symptom severity. At 6 months postoperatively, 70 patients completed repeat GERD-HRQL, LPR-RSI, and EHAS surveys. We then analyzed for surgical and patient-related factors associated with improvement in the 6-month postoperative GERD-HRQL and LPR-RSI scores. RESULTS: There was a statistically significant decrease in the GERD-HRQL (25 vs. 2, p < 0.001), LPR-RSI (17 vs. 3, p < 0.001) and EHAS (34 vs. 15, p < 0.001) 6 months after LARS. On multivariable linear regression, a higher baseline EHAS score was independently associated with a greater improvement in GERD-HRQL (ß 0.35, p < 0.001) and LPR-RSI (ß 0.19, p = 0.03) 6-months after LARS. Additionally, the degree of improvement in EHAS, GERD-HRQL, and LPR-RSI was not influenced by the type of LARS performed or by the severity of disease. CONCLUSION: These findings are consistent with literature suggesting that measures of psychoemotional health correlate better with symptom intensity than objective pathology. We found that patients with a higher EHAS score have greater symptom severity and lower quality of life at baseline. Novel findings to this study are that patients with a higher preoperative EHAS, a measure of psychoemotional health, actually benefitted more from surgery and not less, which has been the traditional view in the literature. Future studies are warranted to establish directionality and explore the role of preoperative cognitive behavioral therapy with LARS for patients with significant symptoms of hypervigilance and anxiety.

Effect of Isoleucine and Added Valine on Performance, Nutrients Digestibility and Gut Microbiota Composition of Pigs Fed with Very Low Protein Diets.

Little is known whether a combination Ile and added Val improves the growth of pigs offered very low protein (VLP) diets through changes in nutrients digestibility and gut microbiota. The objective of this study was to investigate the effect of a mixture of Val above and Ile at NRC levels on growth, nutrient digestibility and gut microbiota in pigs fed with VLP diets. Forty, weaned piglets were assigned to: positive control: normal-protein-diet; negative control (NC): VLP diet supplemented with first four limiting amino acids; VA: NC with Val above NRC; IL: NC with Ile at NRC level; VAIL: NC with Val above and Ile at NRC levels. While both VAIL and VA groups completely recovered the inhibitory effects of VLP diets on feed intake, only VAIL partially recovered the negative effects of VLP diets on growth performance. VAIL and VA increased the thermal radiation and decreased the digestibility of nitrogen. NC increased the relative abundance of Pasteurellaceae and Enterobacteriaceae in the colon. VAIL had a higher abundance of colonic Actinobacteria, Enterococcus, and Brevibacillus and the colon content of VA was more enriched with Mogibacterium. Overall, VAIL partially improved the growth performance which is likely linked with alterations in gut microbiota composition.

Clerkship Roles and Responsibilities in a Rapidly Changing Landscape: a National Survey of Internal Medicine Clerkship Directors.

BACKGROUND: In the rapidly changing landscape of undergraduate medical education (UME), the roles and responsibilities of clerkship directors (CDs) are not clear. OBJECTIVE: To describe the current roles and responsibilities of Internal Medicine CDs. DESIGN: National annual Clerkship Directors in Internal Medicine (CDIM) cross-sectional survey. PARTICIPANTS: One hundred twenty-nine clerkship directors at all Liaison Committee on Medical Education accredited US medical schools with CDIM membership as of September 1, 2017. MAIN MEASURES: Responsibilities of core CDs, including oversight of other faculty, and resources available to CDs including financial support and dedicated time. KEY RESULT: The survey response rate was 83% (107/129). Ninety-four percent of the respondents oversaw the core clerkship inpatient experience, while 47.7% (n = 51) and 5.6% (n = 6) oversaw the outpatient and longitudinal integrated clerkships respectively. In addition to oversight, CDs were responsible for curriculum development, evaluation and grades, remediation, scheduling, student mentoring, and faculty development. Less than one-third of CDs (n = 33) received the recommended 0.5 full-time equivalent (FTE) support for their roles, and 15% (n = 16) had less than 20% FTE support. An average 0.41 FTE (SD .2) was spent in clinical work and 0.20 FTE (SD .21) in administrative duties. Eighty-three percent worked with other faculty who assisted in the oversight of departmental UME experiences, with FTE support varying by role and institution. Thirty-five percent of CDs (n = 38) had a dedicated budget for managing their clerkship. CONCLUSIONS: The responsibilities of CDs have increased in both number and complexity since the dissemination of previous guidelines for expectations of and for CDs in 2003. However, resources available to them have not substantially changed.

A case study of 10 patients administered HBOC-201 in high doses over a prolonged period: outcomes during severe anemia when transfusion is not an option.

BACKGROUND: Hemoglobin-Based Oxygen Carriers (HBOCs) can act as an "oxygen bridge" in acute severe anemia when transfusion is indicated, but not possible. We present data on 10 Expanded Access (EA) patients treated with high cumulative doses of Hemopure (HBOC-201), to assess the ability of HBOC-201 to safely treat life threatening anemia in situations where high volumes of product were administered over an extended period of time. STUDY DESIGN AND METHODS: Inclusion in this study required that the patient receive at least 10 units of HBOC-201 between 2014 and 2017 under the FDA-sanctioned EA program. Depending on a patient's geographical location, treatment with HBOC-201 was obtained through either a single patient emergency Investigational New Drug (IND) application, or an intermediate size population IND. Of the 41 patients who were treated during this period, 10 patients received 10 or more units of the product. Data were obtained from medical records. RESULTS: Treatments with HBOC-201 started within 24 hours of signing consent and were administered at an average rate of 1.99 (SD 0.17) units per day over a mean of 8.2 days (SD 2.9), during which patients received on average 16.2 units (SD 5.7 units) of HBOC-201. The median pre-treatment nadir corpuscular hemoglobin (Hb) concentration was 3.3 (SD 0.9) g/dL and post-treatment Hemoglobin was 7.3 (SD 1.7) g/dL. Common side effects included methemoglobinemia, gastrointestinal symptoms, and hypertension. However, no product-related serious adverse events (SAEs) were noted. All patients survived. CONCLUSIONS: Administration of HBOC-201 over an extended period is a feasible and safe oxygen bridge for severely anemic patients who cannot be transfused with RBC.

Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology.

Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2. In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.

A phase I study of lenalidomide plus chemotherapy with idarubicin and cytarabine in patients with relapsed or refractory acute myeloid leukemia and high-risk myelodysplastic syndrome.

Patients with relapsed/refractory (R/R) acute myeloid leukemia (AML) have poor outcomes and hematopoietic cell transplantation (HCT) is the only curative treatment. New targeted therapies improved survival in select patients with specific mutations, however management of patients without these molecular alterations is an unmet need. We conducted a phase one study of lenalidomide in combination with cytarabine/idarubicin salvage chemotherapy in patients with R/R AML and high-risk myelodysplastic syndromes. A total of 33 patients were enrolled in the study (30 AML, 3 MDS), and treated at three dose levels with 3 + 3 design. Dose-limiting toxicity (DLT) was seen in eight patients, including four hematologic DLTs. The most commonly observed non-hematologic serious adverse events were febrile neutropenia, rash, sepsis and renal injury. Dose level -1, consisting of 25 mg/d lenalidomide D1-21, 1 g/m2 cytarabine D5-8, and 8 mg/m2 idarubicin D5-7 was determined to be the maximum tolerated dose. Note, 15/33 (45%) of patients were able to receive pre-planned 21 days of lenalidomide. Overall, 18 patients achieved complete remission (CR) (n = 14) or CR with incomplete count recovery (CRi) (n = 4) with total CR/CRi rate of 56%. The 1-year and 2-year overall survival (OS) were 24% and 10%, respectively. Among responders, 10/18 underwent allogeneic HCT and had a 1-year OS of 40%. There was no molecular pattern associated with response. These data demonstrate that the combination had clinical activity in R/R AML. This regimen should be further investigated for patients who relapsed after HCT, and as a bridge therapy to HCT. (ClinicalTrials.gov identifier: NCT01132586).

Establishing Mayo Clinic's Coronavirus Disease 2019 Virtual Clinic: A Preliminary Communication.

The coronavirus disease 2019 (COVID-19) pandemic is taking a massive toll on health care systems globally. We developed the COVID-19 virtual clinic (CVC) in conjunction with drive through testing to cope with this situation. There are two arms of the CVC: (1) a screening arm and (2) positive patient arm. Screening is performed over the phone based on the Centers for Disease Control and Prevention screening guideline. Positive patients are followed at regular intervals by video appointments where concerns can be addressed by a provider while also tracking symptom progression. We enrolled 63 positive patients out of 1,153 screened for COVID-19 as of this writing. The CVC continues to address patients' concerns and symptoms in an effort to minimize emergency department and hospital patient volumes, as incidence increases. Drive through testing in conjunction with a virtual clinic allows us to provide high-quality care in an anxious time without consuming excessive personal protective equipment or unnecessarily exposing health care workers. This article could serve as a model to guide other practices to cope with this and future pandemics.

Systematic survey of the function of ROP regulators and effectors during tip growth in the moss Physcomitrella patens.

Rho/Rac of plants (ROP) GTPases are plant-specific small GTPases that regulate cell morphology. ROP activity is controlled by several families of regulatory proteins. However, how these diverse regulators contribute to polarized growth remains understudied. In a system-wide approach, we used RNAi to silence each gene family of known ROP regulators in the juvenile tissues of the moss Physcomitrella patens. We found that the GTPase activating proteins, but not the ROP enhancers, are essential for tip growth. The guanine exchange factors (GEFs), which are comprised of ROPGEFs and Spikes, both contribute to growth. However, silencing Spikes results in less-polarized plants as compared to silencing ROPGEFs, suggesting that Spikes contribute more to establishing cell polarity. Silencing the single-gene family of guanine dissociation inhibitors also inhibits growth, resulting in small, unpolarized plants. In contrast, silencing the ROP effector ROP-interactive CRIB-containing (RIC) protein, which is encoded by a single gene, results in plants larger than the controls, suggesting that RIC functions to inhibit tip growth in moss. Taken together, this systematic loss-of-function survey provides insights into the function of ROP regulators during polarized growth.

Dose, schedule, safety, and efficacy of guadecitabine in relapsed or refractory acute myeloid leukemia.

BACKGROUND: Outcomes for patients with relapsed or refractory acute myeloid leukemia (AML) are poor. Guadecitabine, a next-generation hypomethylating agent, could be useful in treating such patients. METHODS: In this multicenter, open-label, phase 2 dose-expansion study, AML patients from 10 North American medical centers were first randomized (1:1) to receive subcutaneous guadecitabine at 60 or 90 mg/m2 on 5 consecutive days in each 28-day cycle (5-day regimen). Subsequently, another cohort was treated for 10 days with 60 mg/m2 (10-day regimen). RESULTS: Between June 15, 2012, and August 19, 2013, 108 patients with previously treated AML consented to enroll in the study, and 103 of these patients were treated; 5 patients did not receive the study treatment. A total of 103 patients were included in the safety and efficacy analyses (24 and 26 patients who were randomly assigned to 60 and 90 mg/m2 /d, respectively [5-day regimen] and 53 patients who were assigned to 60 mg/m2 /d [10-day regimen]). The 90 mg/m2 dose showed no benefit in clinical outcomes in comparison with 60 mg/m2 in the randomized cohort. Composite complete response (CRc) and complete response (CR) rates were higher with the 10-day regimen versus the 5-day regimen (CRc, 30.2% vs 16.0%; P = .1061; CR, 18.9% vs 8%; P = .15). Adverse events (grade ≥ 3) were mainly hematologic, with a higher incidence on the 10-day regimen. Early all-cause mortality was low and similar between regimens. Twenty patients (8 on the 5-day regimen and 12 on the 10-day regimen) were bridged to hematopoietic cell transplantation. CONCLUSIONS: Guadecitabine has promising clinical activity and an acceptable safety profile and thus warrants further development in this population. Cancer 2018;124:325-34. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

A novel regimen for relapsed/refractory adult acute myeloid leukemia using a KMT2A partial tandem duplication targeted therapy: results of phase 1 study NCI 8485.

KMT2A partial tandem duplication occurs in approximately 5-10% of patients with acute myeloid leukemia and is associated with adverse prognosis. KMT2A wild type is epigenetically silenced in KMT2A partial tandem duplication; re-expression can be induced with DNA methyltransferase and/or histone deacetylase inhibitors in vitro, sensitizing myeloid blasts to chemotherapy. We hypothesized that epigenetic silencing of KMT2A wildtype contributes to KMT2A partial tandem duplication-associated leukemogenesis and pharmacologic re-expression activates apoptotic mechanisms important for chemoresponse. We developed a regimen for this unique molecular subset, but due to relatively low frequency of KMT2A partial tandem duplication, this dose finding study was conducted in relapsed/refractory disease regardless of molecular subtype. Seventeen adults (< age 60) with relapsed/refractory acute myeloid leukemia were treated on study. Patients received decitabine 20 milligrams/meter2 daily on days 1-10 and vorinostat 400 milligrams daily on days 5-10. Cytarabine was dose-escalated from 1.5 grams/meter2 every 12 hours to 3 grams/meter2 every 12 hours on days 12, 14 and 16. Two patients experienced dose limiting toxicities at dose level 1 due to prolonged myelosuppression. However, as both patients achieved complete remission after Day 42, the protocol was amended to adjust the definition of hematologic dose limiting toxicity. No further dose limiting toxicities were found. Six of 17 patients achieved complete remission including 2 of 4 patients with KMT2A partial tandem duplication. Combination therapy with decitabine, vorinostat and cytarabine was tolerated in younger relapsed/refractory acute myeloid leukemia and should be explored further focusing on the KMT2A partial tandem duplication subset. (clinicaltrials.gov identifier 01130506).

Systemic Mastocytosis, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.

Mastocytosis is a group of heterogeneous disorders resulting from the clonal proliferation of abnormal mast cells and their accumulation in the skin and/or in various extracutaneous organs. Systemic mastocytosis is the most common form of mastocytosis diagnosed in adults, characterized by mast cell infiltration of one or more extracutaneous organs (with or without skin involvement). The identification of KIT D816V mutation and the emergence of novel targeted therapies have significantly improved the diagnosis and treatment of systemic mastocytosis. However, certain aspects of clinical care, particularly the diagnosis, assessment, and management of mediator-related symptoms continue to present challenges. This manuscript discusses the recommendations outlined in the NCCN Guidelines for the diagnosis and management of patients with systemic mastocytosis.

Point Prevalence and Patterns of Mental Health Comorbidity Among People Accessing Australia's First Older Adult-Specific Alcohol and Other Drug Treatment Service.

OBJECTIVE: There are good data regarding the prevalence and patterns of dual diagnosis among the general population; however, data regarding the older adult cohort are limited. We aimed to extend the knowledge of the point prevalence and patterns of dual diagnosis among older adults and the impact of dual diagnosis on the utilization of alcohol and other drug treatment services. METHOD: A 12-month medical chart audit of clients discharged from an Australian older adult-specific alcohol and other drug treatment service was performed. Measures included the Alcohol Use Disorders Identification Test-Consumption, the Drug Use Disorders Identification Test-Consumption, the Kessler 10, and the Modified MINI Screen. Additional data collected included mental health diagnoses, number of session types, and treatment outcomes. RESULTS: There were 79 (n = 45, 57% male) medical charts audited, with a mean age of 65.9 years (SD = 5.8). There were 68 (89%) clients having at least one comorbid mental illness. Clients with a dual diagnosis were younger (p = .011) than those without. Some comorbid mental health conditions were associated with additional service utilization (p < .05). Clients with personality disorders required more telephone calls and outreach services (p < .05). The number of mental health diagnoses was associated with additional treatment sessions (p < .05). CONCLUSIONS: Further research with a larger sample size of older adults seeking age-specific alcohol and other drug treatment services is required. Older adult-specific alcohol and other drug treatment services need to allow for longer episodes of care for clients with certain dual diagnoses and a focus on reducing anxiety to increase treatment retention.