Richard P. Levy

JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis

BACKGROUNDnTreatment options for myelofibrosis are limited. We evaluated the efficacy and safety of ruxolitinib, a potent and selective Janus kinase (JAK) 1 and 2 inhibitor, as compared with the best available therapy, in patients with myelofibrosis.nnnMETHODSnWe assigned 219 patients with intermediate-2 or high-risk primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis to receive oral ruxolitinib or the best available therapy. The primary end point and key secondary end point of the study were the percentage of patients with at least a 35% reduction in spleen volume at week 48 and at week 24, respectively, as assessed with the use of magnetic resonance imaging or computed tomography.nnnRESULTSnA total of 28% of the patients in the ruxolitinib group had at least a 35% reduction in spleen volume at week 48, as compared with 0% in the group receiving the best available therapy (P<0.001); the corresponding percentages at week 24 were 32% and 0% (P<0.001). At 48 weeks, the mean palpable spleen length had decreased by 56% with ruxolitinib but had increased by 4% with the best available therapy. The median duration of response with ruxolitinib was not reached, with 80% of patients still having a response at a median follow-up of 12 months. Patients in the ruxolitinib group had an improvement in overall quality-of-life measures and a reduction in symptoms associated with myelofibrosis. The most common hematologic abnormalities of grade 3 or higher in either group were thrombocytopenia and anemia, which were managed with a dose reduction, interruption of treatment, or transfusion. One patient in each group discontinued treatment owing to thrombocytopenia, and none discontinued owing to anemia. Nonhematologic adverse events were rare and mostly grade 1 or 2. Two cases of acute myeloid leukemia were reported with the best available therapy.nnnCONCLUSIONSnContinuous ruxolitinib therapy, as compared with the best available therapy, was associated with marked and durable reductions in splenomegaly and disease-related symptoms, improvements in role functioning and quality of life, and modest toxic effects. An influence on overall survival has not yet been shown. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT00934544.).

Localized disorders in myocardial contraction. Asynergy and its role in congestive heart failure.

CONGESTIVE heart failure has usually been considered to be a global affection of the myocardium in which disturbance of contraction in one or both ventricles is generalized. On the other hand, abnormal myocardial contraction may be caused by local areas of malfunctioning myocardium interacting with other areas of completely normal muscle. The possibility that unco-ordinated contraction of the heart results from such a combination of normal and abnormal muscle has received little attention. In 1925 Wiggers1 described the pattern of left ventricular contraction as a series of sequential fractionate contractions of muscle bundles. He suggested that disturbance in this temporal .xa0.xa0.

Coexistent Idiopathic Thrombocytopenic Purpura and Hyperthyroidism

Excerpt Since 1931, sporadic reports have appeared noting an apparent association between hyperthyroidism and idiopathic thrombocytopenic purpura (ITP) (1-4). During a recent survey of our patients...

The value of a single injection of thyrotropin in the diagnosis of obscure hypothyroidism.

ALTHOUGH full-blown myxedema is readily diagnosed, there are many persons in whom a question of hypothyroidism arises, but the clinical picture and customary tests of thyroid function are not suffi...

Human Thyroxine-Binding Globulin Deficiency: A Genetic Study

THE existence of decreased or absent thyroxine-binding globulin in the serums of certain asymptomatic subjects has been recognized since 1959, when the first case was described by Tanaka and Starr.1 In addition to a low serum protein-bound iodine concentration, serums from persons affected demonstrate a decrease or absence of thyroxine-binding globulin on paper electrophoresis, a normal binding capacity for thyroxine by thyroxine-binding prealbumin and an increase in the in vitro resin uptake of radioactive tri-iodothyronine. The disorder presents no clinical symptoms and causes no discernible ill-effects. The low concentration of protein-bound iodine is accompanied by an accelerated turnover of thyroxine, .xa0.xa0.

Acute thyroid poisoning; report of a case.

ALTHOUGH desiccated thyroid is a widely dispensed medication, reports concerning its acute toxicity are sparse. Stanage and Henske,1 studying a series of 472 accidental poisonings in childhood, stated that thyroid was the third most common medication accidentally ingested, but they made no comment regarding any untoward effects that were observed. Jahr2 described 3 children, ranging in age from twenty months to three years, who accidentally took between 2.3 and 2.8 gm. of thyroid without marked side effects. Danowski and his co-workers3 have given large single doses of 1-thyroxine, equivalent to 0.128 gm. (or 2 gr.) of thyroid per kilogram of .xa0.xa0.

Use of the TSH test in the diagnosis of thyroid disorders.

The measurement of the uptake of a tracer dose of I131 by the thyroid gland has become a standard test of thyroid function. When combined with the basal metabolic rate (BMR) and determination of serum protein-bound iodine (PBI), it gives the clinician a more complete picture of thyroid activity than has ever before been available. Yet there are circumstances in which all three of these tests are inadequate. In such instances it is necessary to determine the response of the thyroid gland to stimulation in order to detect an abnormality in its function. For this purpose an additional test is needed, and the TSH test meets the requirements. By following the response of the thyroid uptake of I131 and the PBI to a single injection of thyrotropin (TSH), the ability of the thyroid gland to respond to stimulation can be determined in a satisfactory and practical manner. Previous reports from this clinic (1, 2) have dealt with the value of this test in the diagnosis of obscure hypothyroidism and low thyroid reserv...

American Thyroid Association Statement: Breast Cancer and Thyroid Hormone Therapy

Excerpt Among patients undergoing mammography at a hospital in Detroit, Michigan, the prevalence of breast cancer was higher in women receiving thyroid hormone therapy than in those who were not (1...

Proteinuria and hypothyroidism.

SINCE both hypothyroidism and renal disease may have in common the findings of periorbital edema, lassitude, weakness and anemia, it is of some interest to know whether albuminuria is also encountered in both disorders. Although current textbooks of medicine seem unanimous in stating that albuminuria may often be found in hypothyroidism1 2 3 4 5 a careful review of the literature does not definitely substantiate this. The description of hypothyroidism by Sir William Gull in 1873 reported the urine as normal in the 2 cases described.6 In Murrays review of the life history of the first myxedematous patient treated with thyroid, as quoted by .xa0.xa0.

Jimson Weed Poisoning

Excerpt To the editor: In a recent paper in this journal, Mikolich, Paulson, and Cross (1) described 10 cases of Jimson seed poisoning. They stated, Induction of emesis may be beneficial in the co...