Capture-based targeted sequencing using a T-cell control in myeloid malignancies and idiopathic cytopenias.

We report on a study of next-generation sequencing in 257 patients undergoing investigations for cytopenias. We sequenced bone marrow aspirates using a target enrichment panel comprising 82 genes and used T cells from paired blood as a control. One hundred and sixty patients had idiopathic cytopenias, 81 had myeloid malignancies and 16 had lymphoid malignancies or other diagnoses. Forty-seven of the 160 patients with idiopathic cytopenias had evidence of somatic pathogenic variants consistent with clonal cytopenias. Only 39 genes of the 82 tested were mutated in the 241 patients with either idiopathic cytopenias or myeloid neoplasms. We confirm that T cells can be used as a control to distinguish between germline and somatic variants. The use of paired analysis with a T-cell control significantly reduced the time molecular scientists spent reporting compared to unpaired analysis. We identified somatic variants of uncertain significance (VUS) in a higher proportion (24%) of patients with myeloid malignancies or clonal cytopenias compared to less than 2% of patients with non-clonal cytopenias. This suggests that somatic VUS are indicators of a clonal process. Lastly, we show that blood depleted of lymphocytes can be used in place of bone marrow as a source of material for sequencing.

Diagnosis and evaluation of prognosis of myelofibrosis: a British Society for Haematology guideline

This document represents an update of the British Society for Haematology (BSH) guideline on myelofibrosis (MF) first published in 2012 and updated in 2015.1 This guideline aims to provide healthcare professionals with clear guidance on the diagnosis and prognostic evaluation of primary my-elofibrosis (PMF), as well as post-polycythaemia vera myelo-fibrosis (post-PV MF) and post-essential thrombocythaemia myelofibrosis (post-ET MF). A section on prefibrotic MF is also included. A separate BSH Guideline covers the manage-ment of MF and is published alongside this guideline.

The management of myelofibrosis: a British Society for Haematology guideline

This document represents an update of the British Society for Haematology guideline on Myelofibrosis first published in 2012 and updated in 2015 These guidelines aim to pro-vide healthcare professionals with clear guidance on stratified management for primary myelofibrosis (PMF), as well as post-polycythaemia myelofibrosis (post-PV MF) and postessential thrombocythaemia myelofibrosis (post-ET MF). A separate BSH guideline covers the diagnosis and prognostic evaluation of myelofibrosis and is published alongside this guideline

Outcomes and characteristics of nonmelanoma skin cancers in patients with myeloproliferative neoplasms on ruxolitinib.

ABSTRACT: Nonmelanoma skin cancers (NMSCs) in ruxolitinib-treated patients with myeloproliferative neoplasms behave aggressively, with adverse features and high recurrence. In our cohort, mortality from metastatic NMSC exceeded that from myelofibrosis. Vigilant skin assessment, counseling on NMSC risks, and prospective ruxolitinib-NMSC studies are crucial.

CNL and aCML should be considered as a single entity based on molecular profiles and outcomes.

Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders that are challenging with regard to diagnosis and clinical management. To study the similarities and differences between these disorders, we undertook a multicenter international study of one of the largest case series (CNL, n = 24; aCML, n = 37 cases, respectively), focusing on the clinical and mutational profiles (n = 53 with molecular data) of these diseases. We found no differences in clinical presentations or outcomes of both entities. As previously described, both CNL and aCML share a complex mutational profile with mutations in genes involved in epigenetic regulation, splicing, and signaling pathways. Apart from CSF3R, only EZH2 and TET2 were differentially mutated between them. The molecular profiles support the notion of CNL and aCML being a continuum of the same disease that may fit best within the myelodysplastic/myeloproliferative neoplasms. We identified 4 high-risk mutated genes, specifically CEBPA (ß = 2.26, hazard ratio [HR] = 9.54, P = .003), EZH2 (ß = 1.12, HR = 3.062, P = .009), NRAS (ß = 1.29, HR = 3.63, P = .048), and U2AF1 (ß = 1.75, HR = 5.74, P = .013) using multivariate analysis. Our findings underscore the relevance of molecular-risk classification in CNL/aCML as well as the importance of CSF3R mutations in these diseases.

Eating Disorder Day Programs: Is There a Best Format?

The use of a Day Program (DP) format (i.e., intensive daily treatment with no overnight admission) has been shown to be an effective treatment for eating disorders (EDs). The disadvantages, however, include higher cost than outpatient treatment (including costs of meals and staff), greater disruption to patients' lives, and the use of a highly structured and strict schedule that may interrupt the development of patients' autonomy in taking responsibility for their recovery. This study investigated whether reducing costs of a DP and the disruption to patients' lives, and increasing opportunity to develop autonomy, impacted clinical outcomes. Three sequential DP formats were compared in the current study: Format 1 was the most expensive (provision of supported dinners three times/week and extended staff hours); Format 2 included only one dinner/week and provision of a take-home meal. Both formats gave greater support to patients who were not progressing well (i.e., extended admission and extensive support from staff when experiencing feelings of suicidality or self-harm). Format 3 did not provide this greater support but established pre-determined admission lengths and required the patient to step out of the program temporarily when feeling suicidal. Fifty-six patients were included in the analyses: 45% were underweight (body mass index (BMI) < 18.5), 96.4% were female, 63% were given a primary diagnosis of anorexia nervosa (or atypical anorexia nervosa), and mean age was 25.57 years. Clinical outcomes were assessed using self-reported measures of disordered eating, psychosocial impairment, and negative mood, but BMI was recorded by staff. Over admission, 4- and 8-week post-admission, and discharge there were no significant differences between any of the clinical outcomes across the three formats. We can tentatively conclude that decreasing costs and increasing the opportunities for autonomy did not negatively impact patient outcomes, but future research should seek to replicate these results in other and larger populations that allow conclusions to be drawn for different eating disorder diagnostic groups.

Prostate SBRT using O-Ring Halcyon Linac - Plan quality, delivery efficiency, and accuracy.

Cone beam CT-guided prostate stereotactic body radiotherapy (SBRT) treatment on the recently installed novel O-ring coplanar geometry Halcyon Linac with a single energy 6MV-flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for early stage low- and intermediate-risk prostate cancer patients. Following the RTOG-0938 compliance criteria and utilizing two-full arc geometry, VMAT prostate SBRT plans were generated for ten consecutive patients using advanced Acuros-based algorithm for heterogeneity corrections with Halcyon couch insert. Halcyon VMAT plans with the stacked and staggered multileaf collimators (MLC) produced highly conformal SBRT dose distributions to the prostate, lower intermediate dose spillage and similar dose to adjacent organs-at-risks (OARs) compared to SBRT-dedicated Truebeam VMAT plans. Due to lower monitor units per fraction and less MLC modulation through the target, the Halcyon VMAT plan can deliver prostate SBRT fractions in and overall treatment time of less than 10 minutes (for 36.25 Gy in five fractions), significantly improving patient compliance and clinic workflow. Pretreatment quality assurance results were similar to Truebeam VMAT plans. We have implemented Halcyon Linac for prostate SBRT treatment in our institution. We recommend that others use Halcyon for prostate SBRT treatments to expand the access of curative hypofractionated treatments to other clinics only equipped with a Halcyon Linac. Clinical follow-up results for patients who underwent prostate SBRT treatment on our Halcyon Linac is underway.

Entrapment Neuropathy Causing Persistent Headache Symptoms after Nonsurgical Rhinoplasty.

The frequency of nonsurgical rhinoplasty has increased in recent years. The occurrence of headaches or migraine symptoms, and their treatment following nonsurgical rhinoplasty, have been scarcely described in the literature. Here, we present a patient who presented with subjective complaints of a new onset headache immediately after nonsurgical rhinoplasty, with subsequent reversal of her symptoms using hylauronidase. Furthermore, a literature review was conducted to establish a possible anatomical pathophysiologic mechanism of these symptoms seen in this patient. METHODS: A case report of a patient who developed persistent headache symptoms after nonsurgical rhinoplasty, with reversal of symptoms using hylaronidase, is described. A literature review of studies on patients developing headaches or migraine-like symptoms after nonsurgical rhinoplasty was conducted, along with a review of the anatomic causes of migraines. RESULTS: Of the 147 relevant citations identified in our search, only 1 individual case report describes a patient who developed a migraine headache after undergoing a nonsurgical rhinoplasty via an injection of hyaluronic acid filler. This was promptly resolved with the utilization of a hyaluronidase injection. The majority of the relevant articles in our search focused on the alarming and most feared complication of vascular compromise of the nasal tissue and intravascular embolization. Within the literature, there was no case series of nonsurgical-rhinoplasty-induced migraines taking into account our inclusion criteria. CONCLUSIONS: This article demonstrates the paucity of literature regarding nonsurgical-rhinoplasty-induced headaches. Although a causation effect cannot be linked, our study highlights a rare phenomenon associated with this ever-increasing aesthetic procedure.

Efficiency and Health Economic Evaluations of BD OneFlow™ Flow Cytometry Reagents for Diagnosing Chronic Lymphoid Leukemia.

REASON FOR THE STUDY: To standardize the use of flow cytometry for classifying hematological malignancies and make the results reliable and reproducible across laboratories, the EuroFlow™ Consortium published a comprehensive specification of antibody-fluorochrome conjugates, standard protocols, and algorithms for analysis. The BD OneFlow™ system builds on, and further standardizes, the EuroFlow protocols. We aimed to assess the effects on safety, efficiency, and costs for laboratories of adopting the BD OneFlow reagent tubes (LST and B-CLPD T1) for diagnosing chronic lymphocytic leukemia. METHODS: We compared in-house laboratory processes and results with those using the LST and B-CLPD T1 reagent tubes with, and without, blood film morphology. Outcome measures included concordance in classification results, and efficiency within the laboratory, that is, resource usage, staff time, unwanted events, and cost-consequences. RESULTS: There was 100% concordance between the classifications made with in-house flow cytometry and those with the BD OneFlow reagent tubes. Using BD OneFlow tubes required 13 hours less staff time per month (i.e. for 100 samples) than the in-house process. Sensitivity analyses explored the effects of uncertainties in the price of the BD OneFlow tubes and the prevalence of CLL and identified the thresholds at which laboratories might expect cost-savings from adopting the BD OneFlow system. Laboratory and clinical staff considered the BD OneFlow system to be safe and effective. CONCLUSIONS: Laboratories adopting the BD OneFlow system for classifying patients with suspected CLL can expect safe, efficient processes that can be cost saving if the discount on the list price, and prevalence of CLL (which will both vary between sites and countries), is within the thresholds suggested by the health economics sensitivity analysis. © 2019 International Clinical Cytometry Society.

Clinical Value of Single-photon Emission Computed Tomography Combined With Computed Tomography for Sentinel Lymph Node Identification in Melanoma.

INTRODUCTION: Melanoma is the deadliest form of skin cancer and has the ability to metastasize widely. Accurate diagnosis of sentinel lymph nodes (SLN) is crucial to its management. The gold standard for SLN identification is planar lymphoscintigraphy. Recently, single-photon emission computed tomography combined with computed tomography (SPECT/CT) has been used as a hybrid method to map lymphatic drainage networks. We aim to better characterize the utility of this tool in head and neck melanoma by evaluating its effectiveness in the preoperative setting for melanoma patients undergoing sentinel lymph node biopsy (SLNB). METHODS: We performed a retrospective chart review at the West Haven Veterans Affairs Hospital. Inclusion criteria were patients with melanoma with a thickness greater than 0.75 mm and SPECT/CT use before operative sentinel lymph node excision. Exclusion criteria included clinically palpable lymph nodes, evidence of distant metastatic disease, melanoma with a Breslow depth less than 0.75 mm, and melanoma in situ. Our primary endpoints were correlation with intraoperative findings and whether the test had any influence on the operative plan. RESULTS: Thirty-five patients between 2011 and 2017 met our criteria. SPECT/CT correlated with the sentinel node biopsy based on intraoperative lymphoscintigraphy in 30 (86%) of 35 cases, and there were no changes to the operative plan after SPECT/CT was performed. Sentinel lymph nodes were correctly identified in all 35 cases. CONCLUSIONS: The role of SPECT/CT in SLNB is uncertain. According to some studies, SPECT/CT can help decision making and change surgical approach in up to 35% of patients. However, other studies have reported questionable correlation with intraoperative findings and no added intraoperative value in over 50% of patients. We have demonstrated that preoperative SPECT/CT was consistent with intraoperative findings in 86.0% of cases but did not change the surgical approach for the SLNB. Surveillance over a period of 12 months did not reveal any signs of melanoma recurrence. A possible advantage of SPECT/CT is potentially decreasing costs by lowering operative time. However, financial cost in the literature suggests SPECT/CT is costlier than lymphoscintigraphy and therefore this must be weighed against any potential benefit. Overall, we did not find that SPECT/CT gives added value when compared with lymphoscintigraphy.

Breast Reconstruction Utilizing Buried Dermato-cutaneous Skin Flaps and Immediate Adipocyte Transfer: A Minimally Invasive Autologous Breast Reconstruction Technique.

Autologous breast reconstruction historically required flaps that were invasive, required prolonged operative times and recoveries, and resulted in varying degrees of donor site morbidity. We present our early results with a minimally invasive completely autologous breast reconstruction technique utilizing buried dermato-cutaneous (DMC) flaps and immediate fat grafting. A 25-patient, 43-breast consecutive case series is presented. METHODS: Select patients desiring autologous breast reconstruction who had sufficient breast ptosis and fat donor tissue were offered breast reconstruction with buried folded over DMC flaps with adipocyte transfer (DCAT). A Wise pattern mastectomy was performed, and fat was transferred into an inferiorly based, buried and folded DMC flap. Fat was also immediately grafted into the pectoralis, subpectoral space, and below pectoralis and serratus fascia. Most patients underwent additional fat grafting at 3-month intervals to complete the reconstruction. RESULTS: Twenty-five consecutive patients (43 breasts) underwent the DCAT procedure with 18 (42%) free nipple grafts. Eight patients (8 breasts) had prior breast radiation, and 2 patients (2 breasts) required postmastectomy radiation. Average fat grafted at initial mastectomy was 70 mL per breast (range 50-103 mL). Nineteen patients (76%) underwent additional outpatient fat grafting. Two additional outpatient fat graft sessions (range 0-3) at 3-month intervals completed the reconstruction. Average fat grafted at the second stage was 217 mL (range 50-320 mL). Average follow-up was 20 months from DCAT and 12 months from last fat graft. CONCLUSION: The DCAT procedure appears to provide a minimally invasive, autologous breast reconstruction alternative in select patients.

Immunoassay detection of fly artifacts produced by several species of necrophagous flies following feeding on human blood.

Foraging behavior of necrophagous flies commonly leads to distortion of human bloodstains and production of artifacts that confound reconstruction efforts at crime scenes. Currently there is no reliable method for detection of fly-derived stains or distinction of the artifacts from human bloodstains. To overcome these deficiencies, a confirmatory test was developed based on immunological detection of cathepsin D found in digestive fluids of Musca domestica and Protophormia terraenovae. Anti-serum (anti-md3 serum) was generated toward a 17-amino acid synthetic peptide based upon predicted antigenic amino acid sequences for the propeptide and mature enzyme of cathepsin D proteinase from larvae of M. domestica. The serum was used to test the hypothesis that digestive artifacts produced by an array of necrophagous flies associated with human decomposition could be detected with the immunoassay. Anti-md3 serum was able to bind artifacts from 27 species of flies representing 9 families. The antiserum reacted with both regurgitate and defecatory stains, but not transfer patterns. Stains from 4 fly species displayed no reactivity with anti-serum in dot blot assays. Anti-md3 serum did not bind to either human or bovine blood stains on filter paper. However, when both types of blood were spiked with synthetic md3 peptide the antiserum was able to bind. Dot blot assays displayed positive reactions with stains produced from larvae and teneral adults of Sarcophaga bullata, and with artifacts as old as 7-years after deposition. These observations indicate that the immunoassay permits distinction of artifacts from a wide range of species from human bloodstains, from multiple development stages, and from artifacts that remain at crime scenes for many months to years after deposition. Further work is needed to determine whether the detection of fly artifacts using the antiserum is suitable for non-laboratory conditions.

Telehealth in Plastic Surgery: A Veterans Affairs Hospital Perspective.

BACKGROUND: Telemedicine is a rapidly growing tool since its invention in the 1950s. Recently, it has expanded to the field of plastic surgery. In the Connecticut VA System, there is 1 plastic surgeon at a central location for the state of Connecticut and southern Massachusetts. Our aim was to pilot a telehealth program for plastic surgery consultation within the VA to improve access to subspecialty care. We intend to discuss the value of telehealth as part of consultation services, and assess patient attitudes toward telemedicine. METHODS: Patients in the Connecticut VA System referred for plastic surgery consultation for evaluation of nonurgent diagnoses, such as skin lesions, carpal tunnel syndrome, and chronic wounds, were invited to participate. After being appropriately consented according to Connecticut state law, patients completed a postvisit questionnaire rating their overall satisfaction, quality of interaction, and ability to communicate using a modified 10-point Likert scale. Means were calculated for numerical responses. Preference for future telehealth visits was reported as a percentage. RESULTS: Forty-one of 44 eligible patients elected to participate. Of those patients, 83% (n = 34) stated they prefer telemedicine services for future visits. Patients rated overall satisfaction 9.2/10, overall quality of interaction 9.2/10, ability to communicate 9.3/10, and sound and video quality 8.6/10 and 9.0/10, respectively. CONCLUSION: Remote video telemedicine is a feasible method of plastic surgery consultation and results in high patient satisfaction. Further studies should focus on cost-effectiveness and ways to broaden the use of telehealth services in plastic surgery.

Eliminating Preoperative Lymphoscintigraphy in Extremity Melanomas.

BACKGROUND: Preoperative lymphoscintigraphy (LSG) is an imaging procedure routinely used to identify the draining nodal basin in melanomas. At our institute, we have traditionally performed preoperative LSG followed by intraoperative LSG for logistical and evaluative reasons. We sought to determine if preoperative LSG could be safely eliminated in the treatment of extremity melanomas, which exhibit consistent and predictable lymphatic drainage patterns. METHODS: We reviewed the Yale Melanoma Registry 1308012545 for cutaneous extremity melanomas treated at our institution. From this registry, we calculated the incidence of atypical lymph node drainage patterns outside the axillary and inguinal regions. Based on these data, we eliminated preoperative LSG in 21 cases (8 upper extremities and 13 lower extremities). Additionally, we calculated the potential hospital charge reduction of forgoing preoperative LSG. RESULTS: Upper and lower extremity melanomas treated at our institution exhibited atypical lymph node drainage at a rate of 3.4% and 2.0%, respectively. The sites of atypical drainage were to the epitrochlear and popliteal regions. In all 21 cases where preoperative LSG was eliminated, we were able to correctly identify the sentinel lymph node. The potential hospital charge reduction of forgoing preoperative LSG totaled $2,393. CONCLUSIONS: Preoperative LSG can be safely eliminated in the management of upper and lower extremity melanomas. Exceptions may be considered for primary lesions of the posterior calf, ankle, and heel as well as for patients with history of prior surgery or radiation. Forgoing preoperative LSG results in a hospital charge reduction of $2,393 and provides additional benefits to the patient. Ultimately, there is potential for significant charge reduction if applied across health care systems.