Is a Rapid Recovery Protocol for THA and TKA Associated With Decreased 90-day Complications, Opioid Use, and Readmissions in a Health Safety-net Hospital?

BACKGROUND: Patients treated at a health safety-net hospital have increased medical complexity and social determinants of health that are associated with an increasing risk of complications after TKA and THA. Fast-track rapid recovery protocols (RRPs) are associated with reduced complications and length of stay in the general population; however, whether that is the case among patients who are socioeconomically disadvantaged in health safety-net hospitals remains poorly defined. QUESTIONS/PURPOSES: When an RRP protocol is implemented in a health safety-net hospital after TKA and THA: (1) Was there an associated change in complications, specifically infection, symptomatic deep venous thromboembolism (DVT), symptomatic pulmonary embolism (PE), myocardial infarction (MI), and mortality? (2) Was there an associated difference in inpatient opioid consumption? (3) Was there an associated difference in length of stay and 90-day readmission rate? (4) Was there an associated difference in discharge disposition? METHODS: An observational study with a historical control group was conducted in an urban, academic, tertiary-care health safety-net hospital. Between May 2022 and April 2023, an RRP consistent with current guidelines was implemented for patients undergoing TKA or THA for arthritis. We considered all patients aged 18 to 90 years presenting for primary TKA and THA as eligible. Based on these criteria, 562 patients with TKAs or THAs were eligible. Of these 33% (183) were excluded because they were lost before 90 days of follow-up and had incomplete datasets, leaving 67% (379) for evaluation. Patients in the historical control group (September 2014 to May 2022) met the same criteria, and 2897 were eligible. Of these, 31% (904) were excluded because they were lost before 90 days of follow-up and had incomplete datasets, leaving 69% (1993) for evaluation. The mean age in the historical control group was 61 ± 10 years and 63 ± 10 years in the RRP group. Both groups were 36% (725 of 1993 and 137 of 379) men. In the historical control group, 39% (770 of 1993) of patients were Black and 33% (658 of 1993) were White, compared with 38% (142 of 379) and 32% (121 of 379) in the RRP group, respectively. English was the most-spoken primary language, by 69% (1370 of 1993) and 68% (256 of 379) of the historical and RRP groups, respectively. A total of 65% (245 of 379) of patients in the RRP group had a peripheral nerve block compared with 54% (1070 of 1993) in the historical control group, and 39% (147 of 379) of them received spinal anesthesia, compared with 31% (615 of 1993) in the historical control group. The main elements of the RRP were standardization of preoperative visits, nutritional management, neuraxial anesthesia, accelerated physical therapy, and pain management. The primary outcomes were the proportions of patients with 90-day complications and opioid consumption. The secondary outcomes were length of stay, 90-day readmission, and discharge disposition. A multivariate analysis adjusting for age, BMI, gender, race, American Society of Anaesthesiologists class, and anesthesia type was performed by a staff biostatistician using R statistical programming. RESULTS: After controlling for the confounding variables as noted, patients in the RRP group had fewer complications after TKA than those in the historical control group (odds ratio 2.0 [95% confidence interval 1.3 to 3.3]; p = 0.005), and there was a trend toward fewer complications in THA (OR 1.8 [95% CI 1.0 to 3.5]; p = 0.06), decreased opioid consumption during admission (517 versus 676 morphine milligram equivalents; p = 0.004), decreased 90-day readmission (TKA: OR 1.9 [95% CI 1.3 to 2.9]; p = 0.002; THA: OR 2.0 [95% CI 1.6 to 3.8]; p = 0.03), and increased proportions of discharge to home (TKA: OR 2.4 [95% CI 1.6 to 3.6]; p = 0.01; THA: OR 2.5 [95% CI 1.5 to 4.6]; p = 0.002). Patients in the RRP group had no difference in the mean length of stay (TKA: 3.2 ± 2.6 days versus 3.1 ± 2.0 days; p = 0.64; THA: 3.2 ± 2.6 days versus 2.8 ± 1.9 days; p = 0.33). CONCLUSION: Surgeons should consider developing an RRP in health safety-net hospitals. Such protocols emphasize preparing patients for surgery and supporting them through the acute recovery phase. There are possible benefits of neuraxial and nonopioid perioperative anesthesia, with emphasis on early mobility, which should be further characterized in comparative studies. Continued analysis of opioid use trends after discharge would be a future area of interest. Analysis of RRPs with expanded inclusion criteria should be undertaken to better understand the role of these protocols in patients who undergo revision TKA and THA. LEVEL OF EVIDENCE: Level III, therapeutic study.

Multifunctional Magnetic Oxide-MoS2 Heterostructures on Silicon.

Correlated oxides and related heterostructures are intriguing for developing future multifunctional devices by exploiting their exotic properties, but their integration with other materials, especially on Si-based platforms, is challenging. Here, van der Waals heterostructures of La0.7 Sr0.3 MnO3 (LSMO) , a correlated manganite perovskite, and MoS2 are demonstrated on Si substrates with multiple functions. To overcome the problems due to the incompatible growth process, technologies involving freestanding LSMO membranes and van der Waals force-mediated transfer are used to fabricate the LSMO-MoS2 heterostructures. The LSMO-MoS2 heterostructures exhibit a gate-tunable rectifying behavior, based on which metal-semiconductor field-effect transistors (MESFETs) with on-off ratios of over 104 can be achieved. The LSMO-MoS2 heterostructures can function as photodiodes displaying considerable open-circuit voltages and photocurrents. In addition, the colossal magnetoresistance of LSMO endows the LSMO-MoS2 heterostructures with an electrically tunable magnetoresponse at room temperature. This work not only proves the applicability of the LSMO-MoS2 heterostructure devices on Si-based platform but also demonstrates a paradigm to create multifunctional heterostructures from materials with disparate properties.

Two-Dimensional Layered Materials Meet Perovskite Oxides: A Combination for High-Performance Electronic Devices.

As the Si-based transistors scale down to atomic dimensions, the basic principle of current electronics, which heavily relies on the tunable charge degree of freedom, faces increasing challenges to meet the future requirements of speed, switching energy, heat dissipation, and packing density as well as functionalities. Heterogeneous integration, where dissimilar layers of materials and functionalities are unrestrictedly stacked at an atomic scale, is appealing for next-generation electronics, such as multifunctional, neuromorphic, spintronic, and ultralow-power devices, because it unlocks technologically useful interfaces of distinct functionalities. Recently, the combination of functional perovskite oxides and two-dimensional layered materials (2DLMs) led to unexpected functionalities and enhanced device performance. In this paper, we review the recent progress of the heterogeneous integration of perovskite oxides and 2DLMs from the perspectives of fabrication and interfacial properties, electronic applications, and challenges as well as outlooks. In particular, we focus on three types of attractive applications, namely field-effect transistors, memory, and neuromorphic electronics. The van der Waals integration approach is extendible to other oxides and 2DLMs, leading to almost unlimited combinations of oxides and 2DLMs and contributing to future high-performance electronic and spintronic devices.

Assessment of the Factors Influencing the Patient's Comprehension of the Informed Consent to Interventional Pain Procedures.

Background: Informed consent is the first step of every medical procedure and is considered a standard of care for patients undergoing medical interventions. Our study seeks to evaluate patients' understanding of the procedure they consented to and the factors affecting the degree of understanding. Methods: In this cross-sectional study, we used an anonymous postprocedural questionnaire to assess our patients' understanding of the procedure being performed and their level of satisfaction. It was conducted between June 2021 and January 2022 on every consenting patient who declined English interpreter services and was undergoing a first elective lumbar epidural steroid injection. Results: The mean age of 201 subjects was 57.3 (23-90) years, with a race distribution of Black (44.3%), White (31.8%), and other races (23.9%). 15.9% of our subjects worked in the medical field. Older age and patients identified as Black and other races had a positive correlation with the propensity to predict a poor understanding of consent. This study failed to demonstrate any difference in understanding of informed consent content between the different subgroups when stratified by assigned sex at birth, level of education, and profession. Patients' expectation from the treatment was classified as desperate (will take any help they can) in 78 patients (38.8%), feeling hopeful (expecting partial improvement in their symptoms) in 52 patients (25.9%), and being optimistic (will obtain full recovery from this injection) in 71 patients (35.3%). 192 patients (95.5%) were very satisfied with the consent process. Seven patients (3.5%) stated that they wanted more information, and 2 patients (1.0%) did not understand the explanation. 180 patients (89.6%) were satisfied with the overall experience, while 21 patients (10.4%) were not. The Wilks test (likelihood-ratio test) resulted in a p value of 0.023 and was deemed statistically significant for a relationship between understanding of consent and the satisfaction of the patient from the procedure. Conclusions: Although patients carry a variable expectation of procedures, most patients in our pain clinic have a high level of satisfaction despite having a poor understanding of the procedure provided via informed consent. Although our patients' level of objective comprehension is low, those with a better understanding of the procedure tend to have a more satisfactory experience.

The IL-20RB receptor and the IL-20 signaling pathway in regulating host defense in oral mucosal candidiasis.

Pseudomembranous candidiasis (thrush), erythematous candidiasis, and fungal esophagitis are infections of the barrier mucosa of the upper gastrointestinal tract. The majority of these infections are caused by Candida albicans, an opportunistic fungal pathogen that frequently exists as a harmless commensal on mucosal surfaces lining the gastrointestinal tract. Oral infections are initiated in the superficial stratified squamous epithelium, in which keratinocytes are the most abundant host cells and are the initial points of contact with C. albicans present in saliva. Intrinsic features of oral keratinocytes are likely to play important roles in host defense and tissue homeostasis in oral candidiasis. One understudied pathway that may be important for modulating oral candidiasis is the IL-20 cytokine signaling pathway that employs keratinocyte IL-20RB receptors as ligands for IL-19, IL-20, and IL-24. We report that production of human oral keratinocyte il24 mRNA and protein are stimulated during co-culture with C. albicans. To test the role of the IL-20 family signaling pathway in oral candidiasis, Il20rb-/- mice (lacking the IL-20RB receptor) were compared to wild-type mice in a murine model of oropharyngeal candidiasis. Fungal burdens and percent loss in body weight were determined. Despite comparable fungal burdens, the Il20rb-/- mice exhibited less weight loss over the course of their infection compared to the B6 mice, suggestive of reduced overall disease consequences in the mutant mice. Interference with IL-20 family cytokine signaling may be useful for augmenting the ability of the host to defend itself against pathogens.

Architecting Nanostructured Co-BTC@GO Composites for Supercapacitor Electrode Application.

Herein, we present an innovative graphene oxide (GO)-induced strategy for synthesizing GO-based metal-organic-framework composites (Co-BTC@GO) for high-performance supercapacitors. 1,3,5-Benzene tricarboxylic acid (BTC) is used as an inexpensive organic ligand for the synthesis of composites. An optimal GO dosage was ascertained by the combined analysis of morphology characterization and electrochemical measurement. The 3D Co-BTC@GO composites display a microsphere morphology similar to that of Co-BTC, indicating the framework effect of Co-BTC on GO dispersion. The Co-BTC@GO composites own a stable interface between the electrolyte and electrodes, as well as a better charge transfer path than pristine GO and Co-BTC. A study was conducted to determine the synergistic effects and electrochemical behavior of GO content on Co-BTC. The highest energy storage performance was achieved for Co-BTC@GO 2 (GO dosage is 0.02 g). The maximum specific capacitance was 1144 F/g at 1 A/g, with an excellent rate capability. After 2000 cycles, Co-BTC@GO 2 maintains outstanding life stability of 88.1%. It is expected that this material will throw light on the development of supercapacitor electrodes that hold good electrochemical properties.

Need for aligning the definition and reporting of cytokine release syndrome (CRS) in immuno-oncology clinical trials.

As cancer immunotherapies continue to expand across all areas of oncology, it is imperative to establish a standardized approach for defining and capturing clinically important toxicities, such as cytokine release syndrome (CRS). In this paper, we provide considerations for categorizing the variety of adverse events that may accompany CRS and for recognizing that presentations of CRS may differ among various immunotherapies (e.g., monoclonal antibodies, CAR T cell therapies and T cell engagers, which can include bispecific antibodies and other constructs). The goals of this paper are to ensure accurate and consistent identification of CRS in patients receiving immunotherapies in clinical studies to aid in reporting; enable more precise evaluation of the therapeutic risk-benefit profile and cross-study analyses; support evidence-based monitoring and management of important toxicities related to cancer immunotherapies; and improve patient care and outcomes. These efforts will become more important as the number and variety of molecular targets for immunotherapies broaden and as therapies with novel mechanisms continue to be developed.

Nonreciprocal Transport in a Bilayer of MnBi2Te4 and Pt.

MnBi2Te4 (MBT) is the first intrinsic magnetic topological insulator with the interaction of spin-momentum locked surface electrons and intrinsic magnetism, and it exhibits novel magnetic and topological phenomena. Recent studies suggested that the interaction of electrons and magnetism can be affected by the Mn-doped Bi2Te3 phase at the surface due to inevitable structural defects. Here, we report an observation of nonreciprocal transport, that is, current-direction-dependent resistance, in a bilayer composed of antiferromagnetic MBT and nonmagnetic Pt. The emergence of the nonreciprocal response below the Néel temperature confirms a correlation between nonreciprocity and intrinsic magnetism in the surface state of MBT. The angular dependence of the nonreciprocal transport indicates that nonreciprocal response originates from the asymmetry scattering of electrons at the surface of MBT mediated by magnon. Our work provides an insight into nonreciprocity arising from the correlation between magnetism and Dirac surface electrons in intrinsic magnetic topological insulators.

A Case Report of Epiglottitis in an Adult Patient.

Epiglottitis is historically known to be a disease of childhood. However, since the implementation of the Haemophilus influenzae type B vaccination, there has been an increasing incidence within the adult population. This is a case report of a 36-year-old male who presented to the emergency department (ED) in severe respiratory distress with complaints of a sore throat, shortness of breath, odynophagia, dysphagia, and hoarseness. Physical exam revealed biphasic stridor, tachycardia, tachypnea, and an erythematous uvula. Imaging of his neck revealed findings consistent with epiglottitis containing nonspecific air. The patient was rapidly intubated, started on broad spectrum antibiotics and dexamethasone. He was admitted for intensive medical management with Otolaryngology consultation. This case report highlights the importance of rapid recognition and diagnosis of epiglottitis in an adult population to prevent morbidity and mortality. Topics: Epiglottitis, stridor, odynophagia, dysphagia, Haemophilus influenzae, group C streptococci, thumb-print sign, intubation.

Which Applicant Factors Predict Success in Emergency Medicine Training Programs? A Scoping Review.

BACKGROUND: Program directors (PDs) in emergency medicine (EM) receive an abundance of applications for very few residency training spots. It is unclear which selection strategies will yield the most successful residents. Many authors have attempted to determine which items in an applicant's file predict future performance in EM. OBJECTIVES: The purpose of this scoping review is to examine the breadth of evidence related to the predictive value of selection factors for performance in EM residency. METHODS: The authors systematically searched four databases and websites for peer-reviewed and gray literature related to EM admissions published between 1992 and February 2019. Two reviewers screened titles and abstracts for articles that met the inclusion criteria, according to the scoping review study protocol. The authors included studies if they specifically examined selection factors and whether those factors predicted performance in EM residency training in the United States. RESULTS: After screening 23,243 records, the authors selected 60 for full review. From these, the authors selected 15 published manuscripts, one unpublished manuscript, and 11 abstracts for inclusion in the review. These studies examined the United States Medical Licensing Examination (USMLE), Standardized Letters of Evaluation, Medical Student Performance Evaluation, medical school attended, clerkship grades, membership in honor societies, and other less common factors and their association with future EM residency training performance. CONCLUSIONS: The USMLE was the most common factor studied. It unreliably predicts clinical performance, but more reliably predicts performance on licensing examinations. All other factors were less commonly studied and, similar to the USMLE, yielded mixed results.

A cell-free biosynthesis platform for modular construction of protein glycosylation pathways.

Glycosylation plays important roles in cellular function and endows protein therapeutics with beneficial properties. However, constructing biosynthetic pathways to study and engineer precise glycan structures on proteins remains a bottleneck. Here, we report a modular, versatile cell-free platform for glycosylation pathway assembly by rapid in vitro mixing and expression (GlycoPRIME). In GlycoPRIME, glycosylation pathways are assembled by mixing-and-matching cell-free synthesized glycosyltransferases that can elaborate a glucose primer installed onto protein targets by an N-glycosyltransferase. We demonstrate GlycoPRIME by constructing 37 putative protein glycosylation pathways, creating 23 unique glycan motifs, 18 of which have not yet been synthesized on proteins. We use selected pathways to synthesize a protein vaccine candidate with an α-galactose adjuvant motif in a one-pot cell-free system and human antibody constant regions with minimal sialic acid motifs in glycoengineered Escherichia coli. We anticipate that these methods and pathways will facilitate glycoscience and make possible new glycoengineering applications.

Diffusion and distribution of deuterium in scandium deuteride thin films under irradiation of deuterium ion beam.

Scandium deuteride (ScDx) thin films, as an alternative target for deuterium-deuterium (D-D) reaction, are a very important candidate for detection and diagnostic applications. Albeit with their superior thermal stability, the ignorance of the stability of ScDx under irradiation of deuterium ion beam hinders the realization of their full potential. In this report, we characterize ScDx thin films with scanning electron microscopy (SEM) and X-ray diffraction (XRD), Rutherford backscattering spectroscopy (RBS) and elastic recoil detection analysis (ERDA). We found with increased implantation of deuterium ions, accumulation and diffusion of deuterium are enhanced. Surprisingly, the concentration of deuterium restored to the value before implantation even at room temperature, revealing a self-healing process which is of great importance for the long-term operation of neutron generator.

Impact of Chromosomal Rearrangement upon DNA Methylation Patterns in Leukemia.

Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST). In this study, the DNA methylation profile of CML was more closely related to APL, another myeloid leukemia, than Ph+ ALL. Although DNA methylation profiles were consistent within a specific tumor type, overall DNA methylation profiles were no influenced by BCR-ABL gene translocation in the cancers and tissues studied. We conclude that DNA methylation profiles may reflect the cell of origin in cancers rather than the chromosomal lesions involved in leukemogenesis.

Differentiating Urgent and Emergent Causes of Acute Red Eye for the Emergency Physician.

Patients commonly present with an acute red eye to the emergency department (ED). It is important to distinguish between benign and sight-threatening diagnoses. Here we provide a comprehensive overview on the acute red eye in the ED.

Phase I Study of Fenretinide Delivered Intravenously in Patients with Relapsed or Refractory Hematologic Malignancies: A California Cancer Consortium Trial.

Purpose: A phase I study was conducted to determine the MTD, dose-limiting toxicities (DLT), and pharmacokinetics of fenretinide delivered as an intravenous emulsion in relapsed/refractory hematologic malignancies.Experimental Design: Fenretinide (80-1,810 mg/m2/day) was administered by continuous infusion on days 1 to 5, in 21-day cycles, using an accelerated titration design.Results: Twenty-nine patients, treated with a median of three prior regimens (range, 1-7), were enrolled and received the test drug. Ninety-seven courses were completed. An MTD was reached at 1,280 mg/m2/day for 5 days. Course 1 DLTs included 6 patients with hypertriglyceridemia, 4 of whom were asymptomatic; 2 patients experienced DLT thrombocytopenia (asymptomatic). Of 11 patients with response-evaluable peripheral T-cell lymphomas, two had complete responses [CR, progression-free survival (PFS) 68+ months; unconfirmed CR, PFS 14+ months], two had unconfirmed partial responses (unconfirmed PR, PFS 5 months; unconfirmed PR, PFS 6 months), and five had stable disease (2-12 cycles). One patient with mature B-cell lymphoma had an unconfirmed PR sustained for two cycles. Steady-state plasma levels were approximately 10 mcg/mL (mid-20s µmol/L) at 640 mg/m2/day, approximately 14 mcg/mL (mid-30s µmol/L) at 905 mg/m2/day, and approximately 22 mcg/mL (mid-50s µmol/L) at 1,280 mg/m2/day.Conclusions: Intravenous fenretinide obtained significantly higher plasma levels than a previous capsule formulation, had acceptable toxicities, and evidenced antitumor activity in peripheral T-cell lymphomas. A recommended phase II dosing is 600 mg/m2 on day 1, followed by 1,200 mg/m2 on days 2 to 5, every 21 days. A registration-enabling phase II study in relapsed/refractory PTCL (ClinicalTrials.gov identifier: NCT02495415) is ongoing. Clin Cancer Res; 23(16); 4550-5. ©2017 AACR.

Determinants of Pediatric Psychiatry Length of Stay in 2 Urban Emergency Departments.

OBJECTIVES: Pediatric mental illness poses a significant burden with an overall prevalence of approximately 10%. Increasingly, children with mental disorders seek care in the emergency department (ED). However, the ED is not an ideal setting. Pediatric mental health patients receive limited treatment and experience significantly longer length of stay (LOS) than other patients seen in the ED. This study examines patient and hospital factors associated with LOS and prolonged LOS (PLOS). METHODS: This is a retrospective chart review of patients between the ages of 3 and 17 presenting at 2 participating urban EDs with a psychiatric diagnosis from May 2010 to May 2012. RESULTS: This study includes 939 patients with an average age of 14.1 years and a median LOS of 295 minutes. The diagnosis was the strongest predictor of LOS and PLOS. Patients with a psychotic disorder or suicide attempt or ideation experienced a longer LOS, 35% and 55% increases, respectively, and an increased odds of PLOS (odds ratio, 3.07 and 8.36, respectively). Patient sex, previous history of self-harm, and the daily census were associated with both a longer LOS and PLOS. Ethnicity, site of admission, and year of admission were only associated with LOS. CONCLUSIONS: Diagnosis-specific management factors are the primary determinant of LOS. However, some patient characteristics and hospital operational factors are also associated with LOS. Organizational reforms and an evaluation of the required human and material resources are necessary to improve access to and availability of pediatric mental health care.

Phase 1 study evaluating the safety and pharmacokinetics of pralatrexate in relapsed/refractory advanced solid tumors and lymphoma patients with mild, moderate, and severe renal impairment.

PURPOSE: Pralatrexate is a folate analogue indicated for the treatment of relapsed or refractory peripheral T-cell lymphoma. It has not been formally tested in patients with renal impairment. This study evaluated the pharmacokinetic (PK) profile of pralatrexate in patients with renal impairment and with relapsed/refractory advanced solid tumors and lymphoma. METHODS: This was an open-label, nonrandomized, phase 1 study. Eligible patients received pralatrexate administered as an IV push over 3-5 min once weekly for 6 weeks in 7-week cycles until progressive disease or intolerable toxicity. Four cohorts of 6 patients were planned for a total of 24 patients. Patients with normal renal function (Cohort A), mild (Cohort B), and moderate renal impairment (Cohort C) received 30 mg/m2 pralatrexate once weekly for 6 weeks in 7-week cycles, and patients with severe renal impairment (Cohort D) were to be administered 20 mg/m2 once weekly for 6 weeks. Plasma and urine samples were collected at pre-specified time points to determine the PK profile of pralatrexate in each treatment cohort. Patients were followed for safety and tolerability. RESULTS: A total of 29 patients were enrolled and 27 patients (14 male) received at least 1 dose of pralatrexate. Because of a qualifying toxicity in Cohort C, the starting dose for Cohort D was reduced to 15 mg/m2. Chronic renal impairment led to a decrease in renal clearance of the pralatrexate diastereomers, PDX-10a and PDX-10b, but systemic exposure to these diastereomers was not dramatically affected by renal impairment. Pralatrexate exposure in Cohort D (15 mg/m2) was similar to the exposure in other cohorts (30 mg/m2). No apparent difference in toxicity between the four treatment cohorts was observed, except for an increase in cytopenias in patients with severe renal impairment. CONCLUSION: Pralatrexate exposure, at a dose of 30 mg/m2, in patients with mild or moderate renal impairment was similar to the exposure in patients with normal renal function. For patients with severe renal impairment only, a pralatrexate dose of 15 mg/m2 is recommended.

Development of romiplostim: a novel engineered peptibody.

Thrombopoietin (TPO) is a growth factor that stimulates megakaryocytes to increases platelet counts. Due to concerns around the development of autoantibodies in clinical studies of TPO, a novel peptide that bound the TPO receptor was used to develop a TPO mimetic. This peptide has no shared homology with TPO, and therefore avoids the risk of development of antibodies that cross-react with endogenous TPO. The ability of the artificial peptide to bind and stimulate the TPO receptor was improved by dimerization of the peptide, and the stability of the peptide was improved by linking the peptides to the Fc portion of an antibody. Romiplostim (Nplate, Amgen, Inc, Thousand Oaks, CA) is the first fully engineered fusion of a novel peptide and antibody or "peptibody" that can stimulate platelet production.

A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome.

Patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) may respond to treatment with epigenetic-modifying agents. Histone deacetylase inhibitors may synergize with hypomethylating agents. This phase 1 dose-escalation study was designed to determine the maximum tolerated dose, recommended phase 2 dose, safety and tolerability of vorinostat plus decitabine in patients with relapsed/refractory AML, newly-diagnosed AML, or intermediate- to high-grade MDS. Thirty-four patients received concurrent therapy with decitabine plus vorinostat and 37 received sequential therapy with decitabine followed by vorinostat. Twenty-nine patients had relapsed/refractory AML, 31 had untreated AML and 11 had MDS. The target maximum administered dose (MAD) of decitabine 20 mg/m(2) daily for 5 d plus vorinostat 400 mg/d for 14 d was achieved for concurrent and sequential schedules, with one dose-limiting toxicity (Grade 3 QTc prolongation) reported in the sequential arm. Common toxicities were haematological and gastrointestinal. Responses were observed more frequently at the MAD on the concurrent schedule compared with the sequential schedule in untreated AML (46% vs. 14%), relapsed/refractory AML (15% vs. 0%) and MDS (60% vs. 0%). Decitabine plus vorinostat given concurrently or sequentially appears to be safe and well-tolerated. Concurrent therapy shows promising clinical activity in AML or MDS, warranting further investigation.