Multicenter Study on Physician-Modified Endografts for Thoracoabdominal and Complex Abdominal Aortic Aneurysm Repair.

BACKGROUND: Physician modified endografts (PMEGs) have been widely used in the treatment of complex abdominal aortic aneurysm and thoracoabdominal aortic aneurysm, however, previous data are limited to small single center studies and robust data on safety and effectiveness of PMEGs are lacking. We aimed to perform an international multicenter study analyzing the outcomes of PMEGs in complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. METHODS: An international multicenter single-arm cohort study was performed analyzing the outcomes of PMEGs in the treatment of elective, symptomatic, and ruptured complex abdominal aortic aneurysms and thoracoabdominal aortic aneurysms. Variables and outcomes were defined according to the Society for Vascular Surgery reporting standards. Device modification and procedure details were collected and analyzed. Efficacy outcomes included technical success and safety outcomes included major adverse events and 30-day mortality. Follow-up outcomes included reinterventions, endoleaks, target vessel patency rates and overall and aortic-related mortality. Multivariable analysis was performed aiming at identifying predictors of technical success, 30-day mortality, and major adverse events. RESULTS: Overall, 1274 patients were included in the study from 19 centers. Median age was 74 (IQR, 68-79), and 75.7% were men; 45.7% were complex abdominal aortic aneurysms, and 54.3% were thoracoabdominal aortic aneurysms; 65.5% patients presented electively, 24.6% were symptomatic, and 9.9% were ruptured. Most patients (83.1%) were submitted to a fenestrated repair, 3.6% to branched repair, and 13.4% to a combined fenestrated and branched repair. Most patients (85.8%) had ≥3 target vessels included. The overall technical success was 94% (94% in elective, 93.4% in symptomatic, and 95.1% in ruptured cases). Thirty-day mortality was 5.8% (4.1% in elective, 7.6% in symptomatic, and 12.7% in ruptured aneurysms). Major adverse events occurred in 25.2% of cases (23.1% in elective, 27.8% in symptomatic, and 30.3% in ruptured aneurysms). Median follow-up was 21 months (5.6-50.6). Freedom from reintervention was 73.8%, 61.8%, and 51.4% at 1, 3, and 5 years; primary target vessel patency was 96.9%, 93.6%, and 90.3%. Overall survival and freedom from aortic-related mortality was 82.4%/92.9%, 69.9%/91.6%, and 55.0%/89.1% at 1, 3, and 5 years. CONCLUSIONS: PMEGs were a safe and effective treatment option for elective, symptomatic, and ruptured complex aortic aneurysms. Long-term data and future prospective studies are needed for more robust and detailed analysis.

Surface-Enhanced Raman Spectroscopy Using a Silver Nanostar Substrate for Neonicotinoid Pesticides Detection.

Surface-enhanced Raman spectroscopy (SERS) has been introduced to detect pesticides at low concentrations and in complex matrices to help developing countries monitor pesticides to keep their concentrations at safe levels in food and the environment. SERS is a surface-sensitive technique that enhances the Raman signal of molecules absorbed on metal nanostructure surfaces and provides vibrational information for sample identification and quantitation. In this work, we report the use of silver nanostars (AgNs) as SERS-active elements to detect four neonicotinoid pesticides (thiacloprid, imidacloprid, thiamethoxam and nitenpyram). The SERS substrates were prepared with multiple depositions of the nanostars using a self-assembly approach to give a dense coverage of the AgNs on a glass surface, which ultimately increased the availability of the spikes needed for SERS activity. The SERS substrates developed in this work show very high sensitivity and excellent reproducibility. Our research opens an avenue for the development of portable, field-based pesticide sensors, which will be critical for the effective monitoring of these important but potentially dangerous chemicals.

Angiogenesis related genes in Takayasu Arteritis (TAK): robust association with Tag SNPs of IL-18 and FGF-2 in a South Asian Cohort.

We performed genetic association study for genes encoding angiogenic and angiostatic proteins in patients with Takayasu arteritis (TAK). A total of 96 SNPs involving 60 genes were studied. Genotyping was performed in Fluidigm 96.96 Dynamic Array chip. All statistical analysis for SNP evaluation was performed using PLINK software. Initial analyses revealed five SNPs from three genes [IL-18 (encodes Interleukin-18), FGF2 (encodes Fibroblast Growth Factor-2), and ANGPT1 (encodes Angiopoietin-1)] as significantly different between controls and cases (uncorrected p < 0.05). After permutation-based analysis, two tag SNPs on the promoter region of IL-18 (rs187238 and rs1946518) and one 3'UTR tag SNP (rs1476217) of FGF2 were significantly associated with susceptibility to TAK, with p and OR (95% CI) of 0.0006 and 1.64 (1.25-2.17), 0.03 and 1.28 (1.02-1.64) & 0.016 and 1.33 (1.05-1.67), respectively; while, the two tag SNPs of ANGPT1 gene (rs6469101 and rs16875900) showed a trend (p = 0.055 & p = 0.051, respectively after permutation based correction). There is robust linkage disequilibrium between the two tag SNPs of IL-18 gene as validated by 1000 genome data of South Asian population; the eQTL effects of these tag SNPs of IL-18 and FGF2 genes on adjacent genes further suggest that these tag SNPs act as genetic risks for development of TAK in South Asians, with possible functional implications towards future biomarker development. Genotype phenotype study by genetic model-based analysis also revealed associations between genotype subsets and clinical features like fever, visual loss, left subclavian and coronary artery involvement in our TAK patients.

Estimating spatially disaggregated probability of severe COVID-19 and the impact of handwashing interventions: The case of Zimbabwe.

INTRODUCTION: The severity of COVID-19 disease varies substantially between individuals, with some infections being asymptomatic while others are fatal. Several risk factors have been identified that affect the progression of SARS-CoV-2 to severe COVID-19. They include age, smoking and presence of underlying comorbidities such as respiratory illness, HIV, anemia and obesity. Given that respiratory illness is one such comorbidity and is affected by hand hygiene, it is plausible that improving access to handwashing could lower the risk of severe COVID-19 among a population. In this paper, we estimate the potential impact of improved access to handwashing on the risk of respiratory illness and its knock-on impact on the risk of developing severe COVID-19 disease across Zimbabwe. METHODS: Spatial generalized additive models were applied to cluster level data from the 2015 Demographic and Health Survey. These models were used to generate continuous (1km resolution) estimates of risk factors for severe COVID-19, including prevalence of major comorbidities (respiratory illness, HIV without viral load suppression, anemia and obesity) and prevalence of smoking, which were aggregated to district level alongside estimates of the proportion of the population under 50 from Worldpop data. The risk of severe COVID-19 was then calculated for each district using published estimates of the relationship between comorbidities, smoking and age (under 50) and severe COVID-19. Two scenarios were then simulated to see how changing access to handwashing facilities could have knock on implications for the prevalence of severe COVID-19 in the population. RESULTS: This modeling conducted in this study shows that (1) current risk of severe disease is heterogeneous across the country, due to differences in individual characteristics and household conditions and (2) that if the quantifiable estimates on the importance of handwashing for transmission are sound, then improvements in handwashing access could lead to reductions in the risk of severe COVID-19 of up to 16% from the estimated current levels across all districts. CONCLUSIONS: Taken alongside the likely impact on transmission of SARS-CoV-2 itself, as well as countless other pathogens, this result adds further support for the expansion of access to handwashing across the country. It also highlights the spatial differences in risk of severe COVID-19, and thus the opportunity for better planning to focus limited resources in high-risk areas in order to potentially reduce the number of severe cases.

Randomized, Double-Blind, Active Comparator Pharmacodynamic Study of Platelet Inhibition with Crushed and Integral Formulations of Clopidogrel and Ticagrelor in Acute Coronary Syndrome.

BACKGROUND: Crushed formulations of specific antiplatelet agents produce earlier and stronger platelet inhibition. We studied the platelet inhibitory effect of crushed clopidogrel in patients with acute coronary syndrome (ACS) and its relative efficacy compared with integral clopidogrel, crushed and integral ticagrelor. OBJECTIVES: We aimed to compare the platelet inhibitory effect of crushed and integral formulations of clopidogrel and ticagrelor in patients with acute coronary syndrome (ACS). METHODS: Overall, 142 patients with suspected ACS were randomly assigned to receive crushed or integral formulations of clopidogrel or ticagrelor. Platelet inhibition at baseline and 1 and 8 h was assessed using the VerifyNow assay. High on-treatment platelet reactivity (HTPR) ≥ 235 P2Y12 reaction units (PRUs) 1 h after the medication loading dose was also determined. RESULTS: The PRU and percentage inhibition median (interquartile range) at 1 h for the different formulations were as follows: crushed clopidogrel: 196.50 (155.50, 246.50), 9.36 (- 1.79, 25.10); integral clopidogrel: 189.50 (159.00, 214.00), 2.32 (- 2.67, 19.89); crushed ticagrelor: 59.00 (10.00, 96.00), 75.53 (49.12, 95.18); and integral ticagrelor: 126.50 (50.00, 168.00), 40.56 (25.59, 78.69). There was no significant difference in PRU or percentage platelet inhibition between the crushed and integral formulations of clopidogrel (p = 0.990, p = 0.479); both formulations of ticagrelor were superior to the clopidogrel formulations (p < 0.05). On paired comparison, crushed ticagrelor showed robust early inhibition of platelets compared with the integral formulation (p = 0.03). Crushed clopidogrel exhibited the maximal HTPR of 34.3%, but was < 3% for both formulations of ticagrelor. CONCLUSIONS: The platelet inhibitory effect of crushed clopidogrel is not superior to integral preparation in patients with ACS. Crushed ticagrelor produced maximal platelet inhibition acutely. HTPR rates in ACS are similar and very low with both formulations of ticagrelor, and maximal with crushed clopidogrel. Clinical Trials Registry of India identifier number CTRI/2020/06/025647.

Suprachoroidal Injection of Triamcinolone Acetonide Injectable Suspension for the Treatment of Macular Edema Associated With Uveitis in the United States: A Cost-Effectiveness Analysis.

OBJECTIVES: Suprachoroidal injection of triamcinolone acetonide is the first Food and Drug Administration-approved treatment for macular edema associated with uveitis. A cost-effectiveness analysis was performed comparing this treatment with best supportive care (BSC) for the management of this indication from US Medicare and commercial payer perspectives. METHODS: A patient-level simulation was developed per the patient characteristics and changes in best-corrected visual acuity letter scores observed in a phase III study of triamcinolone acetonide (PEACHTREE). The wholesale acquisition cost of triamcinolone acetonide was $1650/injection; suprachoroidal injection cost was assumed at $200/injection. Healthcare costs were informed by a US claims-based analysis. Mortality risk associated with severe vision loss and blindness was modeled by applying a hazard ratio to all-cause mortality rates of the US general population. Health-related quality of life weights, obtained from a regression model fitted to the Visual Function Questionnaire-25 data from PEACHTREE, were applied based on the best-corrected visual acuity scores of both eyes. Costs (2020 US dollar) and benefits were discounted at 3% annually. Incremental cost-effectiveness ratios were estimated over a 10-year horizon. RESULTS: In the base-case, the incremental cost-effectiveness ratio comparing triamcinolone acetonide with BSC was $28 479 per quality-adjusted life-year gained. The wholesale acquisition cost for triamcinolone acetonide for suprachoroidal use was ∼68%, ∼56%, and ∼27% below the willingness-to-pay thresholds of $150 000, $100 000, and $50 000 per quality-adjusted life-year gained, respectively. Results were robust in sensitivity and scenario analyses. CONCLUSIONS: Triamcinolone acetonide for suprachoroidal use is cost-effective compared with BSC for patients with macular edema associated with uveitis.

Isolated Cricoid Fracture and Thyroid Hematoma in Blunt Injury of the Neck.

Introduction Blunt trauma to the neck may result in life threatening injuries due to airway compromise. Thyroid Injury in a previously normal gland is rare, so is Isolated Cricoid Fracture. The expanding thyroid hematoma and an unstable larynx compound the effects of compression and lead to sudden deterioration of the patient. Case Report We report the case of young male, who sustained a blunt injury in front of the neck. He developed a swelling in the front of his neck and suddenly deteriorated, needing intubation and airway management. Computed Tomographic imaging of the neck showed thyroid hematoma and fracture of the cricoid ring requiring an emergency hemi thyroidectomy and fixation of the cricoid fracture. Discussion This case brings forth the occurrence of two rare entities, Thyroid hematoma and Isolated Cricoid fracture in the same patient needing expert airway management and exploration.

Takayasu Arteritis: JACC Focus Seminar 3/4.

Takayasu arteritis is a rare idiopathic large-vessel vasculitis that typically affects young women. An early "prepulseless" stage is often missed, associated with nonspecific constitutional symptoms (fever, malaise, and weight loss) and elevated inflammatory markers. Unchecked disease progression leads to the "pulseless" stage, manifest clinically by missing pulses, vascular tenderness, and ischemic symptoms (limb claudication, dizziness, angina, and renovascular hypertension), and is characterized pathologically by arterial wall thickening and stenotic/occlusive lesions or aneurysm formation. Vascular complications (stroke, blindness, heart failure, and aneurysm rupture) could follow unless disease progression is halted by immunosuppressive therapy and critical lesions are palliated by timely endovascular therapy or open surgery. Early diagnosis, effective therapy, and lifelong surveillance for disease activity relapses and vascular disease progression are critical to successful long-term outcomes. The outlook for patients has improved significantly in recent years with the establishment of diagnostic and classification criteria, better investigational modalities, and more effective medical and invasive therapy.

Determination of Total Proteinogenic Amino Acids and Taurine by Pre-column Derivatization and UHPLC: Single Laboratory Validation, First Action Official MethodSM 2019.09.

BACKGROUND: A method has been developed and validated for selective, accurate, and precise determination of total proteinogenic amino acids and taurine from infant formula and adult/pediatric nutritional formulas (powders, ready-to-feed liquids, and liquid concentrates). The method was reviewed by the AOAC INTERNATIONAL SPIFAN Expert Review Panel (ERP) during the 133rd AOAC Annual Meeting and Expo on September 7, 2019 in Denver, CO, USA, and was recommended to First Action Official MethodsSM status. OBJECTIVE: The method involves protein hydrolysis to amino acids, a simple pre-column derivatization of amino acids and separation of derivatized amino acids by UHPLC. The quantification of amino acids is performed by multi-point calibration using norvaline as the internal standard. The analytical method is capable of quantitative determination for 22 proteinogenic amino acids, but cannot be used to quantitate tryptophan, which is destroyed during the acid hydrolysis step. Asparagine is determined as aspartic acid and glutamine as glutamic acid. Cystine and cysteine are converted to S-2-carboxyethylthiocysteine (CYSx) and the derivative is separated from the other amino acids. Citrulline, which is present in some matrixes, is separated from other amino acids and is not included in the method performance evaluation in the single-laboratory validation (SLV). METHOD: The proposed method met all the performance requirement limits set in Standard Method Performance Requirement (SMPR®) 2014.013 for total proteinogenic amino acids and taurine. The correlation coefficient of multi-point calibration was not less than 0.999 for any amino acids at any point in the SLV study, confirming the validity of linear dynamic range (LDR) and linearity of the method. The individual amino acids in the chromatogram were identified by absolute retention time and relative retention time (RRT) with respect to the internal standard norvaline. There were no significant (S/N <10) interferences from the reagents or byproducts of derivatization and targeted matrixes. The method demonstrated high selectivity. RESULT: Accuracy of the method was validated using standard reference materials (SRMs; NIST SRM 1869 and 1849a) and spike recovery studies. The amino acid results in the SRMs were within the ranges of Reference Mass Fraction Values. The accuracy of the method was corroboratively validated by spike recovery studies. The average spike recovery ranged between 93 and 107% ensuring the accuracy of the method for amino acids and compliance with AOAC SMPR 2014.013. CONCLUSIONS: Precision data of the method demonstrate that it meets the stakeholder requirements as per the SMPR. The mean RSDr for all the amino acids for 17 matrixes selected for the SLV were not more than 4%. The method is very sensitive and the LOQ can go down to approximately ten times lower than the SMPR requirements. The sensitivity of method is a direct reflection of its signal-to-noise ratio which ensures guaranteed method performance at the lower levels of amino acids in these matrixes. HIGHLIGHTS: Taurine (aminoethane sulfonic acid), unlike the other amino acids, is a beta-sulfonic amino acid that is not used in protein synthesis but is found as a free amino acid in tissues. The acidic functional group (-COOH) in common amino acids is replaced with a sulfonic acid (-SO3H) group in taurine. The method offers baseline separation of citrulline which is an alpha amino acid generally present in infant formula and adult/pediatric nutritional products. The separation of citrulline eliminates the risk of interference of this compound with other amino acids. The method can also separate and quantitate hydroxyproline, an important component of collagen that is often used to quantitate collagen. The method is simple and does not include any proprietary chemicals or instruments, and it can be performed on any basic reverse phase UHPLC system with UV detection (1-6).

Coronary artery disease management and cost implications with fractional flow reserve guided coronary intervention in Indian patients with stable ischemic coronary artery disease.

OBJECTIVES: To study the safety of stent avoidance, frequency of change in management decisions, and its cost implications while using a fractional flow reserve (FFR)-guided treatment strategy for intermediate-grade coronary artery stenosis. BACKGROUND: The impact of FFR in guiding management decisions and its cost implications has not been studied after imposition of a ceiling on stent prices by the Government of India. METHODS: In 400 patients with 477 intermediate-grade coronary lesions for whom coronary intervention was planned, functional assessment using FFR was done. Incidence of the primary composite endpoint (major adverse cardiac event [MACE], cardiac death, myocardial infarction, objective evidence of ischemia, and target vessel revascularization) in the stent avoided subset was compared with the stented group at follow-up. Micro-costing analysis was done using a computed model with current stent and FFR wire prices. RESULTS: The overall incidence of MACE was 4.9%, 0.9% in the stent-avoided subset and 6.9% in stented group (p = 0.04, comparing the latter two) at a median follow-up of 21 months (interquartile range 12-31 months). Serious adverse events occurred only in 1% of patients receiving adenosine. The average cost saving was Indian rupees (INR) 51,847 [United States Dollar (USD) 746] per patient, resulting in total savings of INR 15,813,379 (USD 227,530). Cost savings persisted but were lower by 36% (INR 18,613/USD 268 per patient) after the ceiling of stent prices. CONCLUSION: FFR-guided percutaneous coronary intervention (PCI) strategy is safe and cost-effective in countries where majority of patients self-finance their health care, resulting in stent and PCI avoidance in approximately one in three patients referred for coronary angioplasty.

Endografts with mini-cuff-augmented fenestrations for endovascular repair of thoracoabdominal aortic and common iliac artery aneurysms.

OBJECTIVE: To report a technique of creating mini-cuff-augmented fenestrations in endografts for use in endovascular aneurysm repair. METHODS: Circular fenestrations are made in Dacron thoracic (Valiant Captivia, Medtronic) or tapered iliac limb (Endurant, Medtronic) endografts using thermal cautery and the edges are strengthened with radio-opaque wire sutured on with 6-0 polypropylene. Straight thin-wall expanded polytetrafluoroethylene vascular graft of the same diameter as the fenestration is affixed to its edge with nonlocking 5-0 polypropylene suture, everted, trimmed, balloon-dilated to its nominal diameter and prevented from invaginating by relaxed external stay sutures. Mini-cuff-augmented fenestrations are often pre-cannulated with looped or externalized nitinol guidewires to facilitate catheter crossing. Successful use of mini-cuff-augmented fenestrations is illustrated in a symptomatic patient with Crawford extent-3 thoracoabdominal aortic and bilateral common iliac artery aneurysm undergoing endovascular repair. Seven mini-cuff-augmented fenestrations were created to preserve flow into five visceral arteries (celiac, superior mesenteric, left and dual right renal; all arising from the aneurysm) and both internal iliac arteries (arising at the aneurysm edge). RESULTS: Effective sealing was achieved immediately at all mini-cuff-augmented fenestrations. At 6-month follow-up there were no endoleaks, all fenestration stents were patent and undistorted, and the aneurysm sac size had decreased. CONCLUSION: Mini-cuff-augmented fenestrations accomplish effective fenestration sealing, despite being in aneurysmal zones, while preserving the advantages of fenestrations over cuffed branches.

Computed Tomographic Validation of the Center-Center Radiographic Technique for Syndesmosis Fixation Axis Alignment in Normal Ankles.

BACKGROUND: Ankle syndesmotic ligament injury is an important factor affecting clinical outcome after lower extremity injury with as little as 2 mm of syndesmotic displacement leading to worse clinical outcome. One important factor is the appropriate placement of clamps and fixation across the syndesmosis. When not ideally aligned, these can result in malalignment of the fibula in the incisura. This study sought to provide computer validation of using the center-center technique to identify an ideal centroid axis for placement of syndesmotic implants. METHODS: Thirty computed tomography (CT) scans of patients from July 1, 2016, to June 30, 2018, with normal syndesmoses were evaluated. Center-center and centroid measurements were drawn and compared on the axial CT images at 10, 20, and 30 mm superior to the tibial plafond. Three observers recorded measurements for the same 50 patients in order to compare interobserver reliability. RESULTS: The difference between the centroid and center-center axis at each height level was a mean 0.4 degrees (range, 0.3-0.5 degrees). The center-center and centroid axis change by externally rotating as the height increases away from the tibial plafond with mean, 3 degrees (range, 0-6.1 degrees). Intraclass correlation coefficients (ICCs) were measured at 0.98, thus demonstrating excellent intraobserver and interobserver reliability on these measurements. CONCLUSION: The center-center technique can be used to identify the centroid axis within an acceptable degree of rotation at heights above the tibial plafond that are relevant to an operating surgeon placing syndesmotic fixation. CLINICAL RELEVANCE: Theoretically, this aligns the centroids of the fibula and tibia, which achieves the same ideal patient-specific alignment and raises the question as to the extent to which the centroid and center-center axes correlate in the general population. If present, a strong correlation has potentially high clinical importance when planning syndesmotic fixation.

Exceptionally large, atypically located spindle cell lipoma.

Spindle cell lipomas are a rare subtype of lipoma typically occurring in the shawl region of middle-aged men with a characteristic histological appearance consisting of mature adipocytes, ropey collagen and spindle cells. Those of extraordinary size or atypical anatomic location require a proper immunohistological workup to rule out more ominous malignancy. The authors report the rare presentation of a 54-year-old man with a large mass of the left palm causing discomfort and paresthesia for 6 months. Radiographs showed a radiolucent mass without mineralisation or bony involvement. MRI demonstrated a non-contrast-enhancing homogeneous lipomatous mass encompassing flexor tendons of the palm. Elective excisional biopsy and immunohistological analysis were consistent with spindle cell lipoma measuring 11 cm × 7 cm × 4 cm. This case is the largest spindle cell lipoma of the hand reported in the literature and appears to be the largest described in the upper extremity.

Clinical and economic analysis of patients with acute myeloid leukemia by FLT3 status and midostaurin use at a Comprehensive Cancer Center.

INTRODUCTION: Identification of cytogenetic and molecular abnormalities has become vital for the appropriate treatment of acute myeloid leukemia (AML). One of the most common molecular alterations in AML is the constitutive activation by internal tandem duplication of FMS-like tyrosine kinase 3 (FLT3). METHODS: This observational, retrospective, cohort study at the Huntsman Cancer Institute (HCI) had two time periods: 1) a historical pre-midostaurin time period which consisted of the FLT3 mutated (FLT3m) and FLT3 wild type (FLT3wt) cohorts from January 1, 2007, to December 31, 2016, and 2) a post-midostaurin cohort which consisted of the FLT3 mutated midostaurin-user cohort (early mido) from May 01, 2017 to December 31, 2018. RESULTS: In total, 39 patients were included in the FLT3m cohort, 61 in the FLT3wt cohort, and seven in the early mido cohort. FLT3m patients spent fewer days in the hospital during the first consolidation regimen and received fewer consolidation cycles compared to FLT3wt patients. Overall survival (OS) was similar between FLT3m and FLT3wt patients. For patients without hematopoietic stem cell transplant, OS was significantly shorter for FLT3m patients compared to FLT3wt patients. Mean AML related inpatient charges and physician charges for FLT3m patients were significantly higher than FLT3wt patients. CONCLUSION: The FLT3 mutation is historically associated with a shorter time to transplant and increased total health care charges. More information is needed to evaluate the real-world treatment strategies for FLT3-mutated patients in the presence of FLT3 inhibitors and the impact of these treatment strategies on clinical and economic outcomes.

Type 3 Coronary Perforation on Optical Coherence Imaging.

OCT imaging revealed a 1.5 mm-long transmural breach in a segment of the artery devoid of calcium or eccentric plaque burden. Focal negative remodeling identified on OCT was deemed the reason for this otherwise unexplained cause of coronary rupture.

Tyrosine kinase inhibitor therapy treatment and discontinuation in patients with chronic myeloid leukemia in chronic phase in the United States: a clinical practice perspective.

Tyrosine kinase inhibitor (TKI) therapy discontinuation practice in patients with chronic myeloid leukemia chronic phase (CML-CP) was assessed in real-world practice prior to the release of recommendations on discontinuation. Data were collected from US oncologists/hematologists (through web-based physician survey and patient chart review) on TKI therapy discontinuation practice including monitoring, adequate response for discontinuation, relapse, and symptoms following discontinuation. From the physician survey, 34% of oncologists/hematologists attempted discontinuation, with two-thirds doing so outside of a trial. From the chart review, TKI therapy was discontinued in 3.4% of patients after they achieved an adequate response with the intention to remain CML-therapy-free until disease relapse. Among these patients, 21% relapsed and 17% had symptoms following discontinuation. There was a lack of consensus on the definition of adequate response suggesting that discontinuation was attempted without clear guidelines and under suboptimal conditions underscoring the need for physician education regarding guidelines for TKI therapy discontinuation.

Cost Effectiveness of Midostaurin in the Treatment of Newly Diagnosed FLT3-Mutated Acute Myeloid Leukemia in the United States.

OBJECTIVES: The aim of this study was to assess the cost effectiveness of midostaurin + cytarabine + daunorubicin (midostaurin arm) versus placebo + cytarabine + daunorubicin (placebo arm) in the treatment of adult patients with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) who are eligible for standard cytarabine + daunorubicin chemotherapy, from a US third-party payer perspective. METHODS: A lifetime partitioned survival model with four health states (active disease, complete remission [CR], relapse, and death) was constructed. Efficacy inputs (time to CR or death, time to relapse or death, and overall survival) were estimated using data from the RATIFY trial (NCT00651261). Costs (inflated to 2016 US dollars) included treatment, drug monitoring, stem cell transplantation (SCT), adverse events costs, and medical costs associated with health states. Incremental costs per quality-adjusted life-year (QALY) and life-year (LY) gained were estimated. Deterministic (DSA) and probabilistic sensitivity analyses (and PSA) were performed to assess model robustness. RESULTS: In the base case, patients in the midostaurin arm incurred higher total direct costs over a lifetime compared with the placebo arm ($4,043,470 vs. $3,959,741), resulting in an incremental cost of $83,729; however, the midostaurin arm had better effectiveness, with 1.59 more LYs and 1.37 more QALYs. These led to a base-case incremental cost-effectiveness ratio (ICER) of $52,596 per LY, or $61,167 per QALY. Results were robust in the DSA. In the PSA, the probability of the midostaurin arm being cost-effective compared with the placebo arm was 65.9%, at a willingness to pay of $150,000/QALY. CONCLUSIONS: This analysis suggests that midostaurin is a cost-effective treatment for adult patients with newly diagnosed FLT3-mutated AML, from a US third-party payer perspective.

Giant epidermal cyst of the arm: a rare presentation.

A giant epidermal cyst is a benign soft tissue mass commonly involving the trunk, hand and face. The authors report a rare presentation of a 69-year-old man who presented with a painful, slow-growing left arm mass for 30 years duration. Examination revealed a large, mobile, soft tissue mass of the lateral aspect of the left arm. MRI showed a large, cystic left arm soft tissue mass. The mass was excised and the diagnosis of a giant epidermal cyst was made based on imaging and histopathology after surgical resection. The mass measured 9.5 cm x 8 cm x 4 cm, which is the largest reported giant epidermal cyst of the upper extremity.