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The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.
ACUTE LEUKEMIA AND MYELODYSPLASTIC SYNDROME
Inotuzumab ozogamicin in acute lymphoblastic leukemia (June 2016)
Inotuzumab ozogamicin is an investigational anti-CD22 monoclonal antibody conjugated to calicheamicin; it has demonstrated activity in relapsed/refractory acute lymphoblastic leukemia (ALL). Early results are available from an international open-label, randomized phase 3 trial that compared inotuzumab ozogamicin versus intensive chemotherapy in 326 patients with relapsed/refractory ALL . Inotuzumab ozogamicin resulted in a higher percentage of patients achieving a complete response (81 versus 29 percent), many of whom attained minimal residual disease negativity. There was a small improvement in median progression-free survival (five versus two months) and overall survival (eight versus seven months). Inotuzumab ozogamicin results in high rates of deep response in this setting, but the majority of patients will relapse if no further therapy is given. Further study is necessary to better elucidate the best way to incorporate this drug into the treatment of patients with ALL. (See "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults", section on 'Inotuzumab ozogamicin'.)
ANEMIA AND OTHER RED CELL DISORDERS
Rhabdomyolysis and sickle cell trait (August 2016)
Sickle cell trait is a benign carrier condition with a normal life expectancy. However, concerns have been raised regarding an increased risk of rhabdomyolysis and sudden death with prolonged physical activity. These risks were addressed in a cohort study of almost 50,000 black soldiers in the United States army for whom sickle cell trait status and other clinical information was available . While the risk of rhabdomyolysis was increased (hazard ratio, 1.5), this magnitude of risk is similar to that conferred by obesity or smoking and less than that due to antipsychotic or statin medications. Mortality was not increased over that in black soldiers without sickle cell trait, and the sole death from rhabdomyolysis occurred in an individual without sickle cell trait. Interventions to reduce exertion-related injuries should be aimed at all athletes and members of the military, regardless of sickle cell trait status. (See "Sickle cell trait", section on 'Rhabdomyolysis and sudden death during strenuous physical activity'.)
CHRONIC LEUKEMIAS AND THE MYELOPROLIFERATIVE NEOPLASMS
Bendamustine plus rituximab versus FCR in CLL (July 2016)
Nonrandomized trials have suggested that the combination of bendamustine plus rituximab (BR) is slightly less effective, but better tolerated than, fludarabine, cyclophosphamide, and rituximab (FCR) for the initial treatment of chronic lymphocytic leukemia (CLL). In a multicenter, open-label noninferiority trial, 564 adults with previously untreated CLL without del(17p) and without significant comorbidities were randomly assigned to FCR versus BR . Despite being associated with more severe toxicities and dose reductions, FCR improved median progression-free survival by approximately 13 months. At a median follow-up of 37 months, this has not yet translated into an improvement in overall survival. FCR remains our preferred treatment regimen for younger adults with previously untreated CLL without del(17p). Given its better tolerability, BR is an acceptable alternative for younger adults with decreased renal function or other comorbidities. (See "Selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia", section on 'Bendamustine-based therapy'.)
Midostaurin in systemic mastocytosis (June 2016)
Case reports have described dramatic responses in patients with systemic mastocytosis (SM) treated with the multikinase/KIT inhibitor midostaurin. Two prospective trials of midostaurin have now described responses in 60 to 70 percent of patients with advanced SM [4,5]. Treatment resulted in reversal of organ damage (cytopenias, liver dysfunction) and decreases in bone marrow mast cell burden and serum tryptase levels. Responses were observed regardless of KIT D816V status, prior therapy, or the presence of an associated hematologic neoplasm. Midostaurin is being evaluated by drug regulatory agencies, but is as yet unavailable. (See "Systemic mastocytosis: Treatment and prognosis", section on 'Midostaurin'.)
Vascular disease in patients with CML taking tyrosine kinase inhibitors (June 2016)
For the initial treatment of chronic myeloid leukemia (CML), the second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib are able to achieve faster and deeper responses than imatinib, but have a different toxicity profile, including increased cardiovascular toxicity. A retrospective cohort study used a Swedish population-based registry to analyze the risk of vascular events in 896 patients with chronic-phase CML treated with imatinib, dasatinib, or nilotinib . When compared with age- and sex-matched controls, patients treated with any TKI had an increased risk of vascular events, but the association was greater with the second-generation agents. Event rates for myocardial infarction among patients treated with nilotinib, dasatinib and imatinib were 29, 19, and 8 per 1000 person-years, respectively. These findings underscore the importance of screening for and optimal management of traditional cardiac risk factors. Although it is not known whether anticoagulation helps, many clinicians offer low-dose aspirin for general cardiovascular prophylaxis in patients taking TKIs. (See "Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia", section on 'Vascular disease'.)
HEMATOPOIETIC CELL TRANSPLANTATION
Umbilical cord blood transplant in minimal residual disease positive AML (September 2016)
For patients with acute myeloid leukemia (AML) undergoing transplant who do not have a related donor, it is not known if the presence of minimal residual disease (MRD) should influence donor choice. In one retrospective study, leukemia patients with MRD prior to transplant had less relapse and better survival with an unrelated umbilical cord blood (UCB) transplant than with peripheral blood progenitor cell or bone marrow from an HLA-matched unrelated donor or an HLA-mismatched unrelated donor . In contrast, a benefit for UCB transplant was not seen among those without MRD. Further analysis suggested that the use of UCB abrogated the negative impact of MRD on patient outcome. Further trials are needed to confirm these findings and evaluate whether other donor groups (eg, haploidentical transplant) impact outcomes in patients with MRD. (See "Donor selection for hematopoietic cell transplantation", section on 'Disease status'.)
Virus-specific T cell infusions for patients with primary immunodeficiencies and hematopoietic cell transplant (June 2016)
Viral infections, particularly with cytomegalovirus, Epstein-Barr virus, and adenovirus, are a leading cause of death in patients with severe combined immunodeficiency (SCID) and other forms of moderate-to-severe primary immunodeficiency (PID), both before and after hematopoietic cell transplantation (HCT). Investigational infusions of virus-specific T cells (VST) from either stem cell donors or third-party donors have been evaluated to treat and/or prevent these life-threatening viral infections. One retrospective series examined 26 patients with a PID requiring HCT who had at least one documented serious viral infection and were treated with VST either before or after HCT . Complete or partial antiviral response was seen in 76 to 100 percent of patients, depending upon the particular virus. An additional 10 patients were treated preventively with VST prior to HCT. Of these, eight remained free of the most common serious viral infections. This therapy is still experimental, but commercial entities are developing these cellular products and they may be available for more widespread use in a few years. (See "Severe combined immunodeficiency (SCID): An overview", section on 'Treatment'.)
HEMOSTASIS AND THROMBOSIS
Risk of inherited thrombophilia and central venous catheter-associated venous thromboembolism in children (September 2016)
The majority of venous thromboembolism (VTE) in children is associated with central venous catheter (CVC) use. The association between inherited thrombophilia (IT) and CVC-related VTE is unclear. A recent systematic review and meta-analysis found that IT is associated with an increased likelihood of CVC-associated VTE (odds ratio 3.2 [95% CI 1.6-6.5]) . However, the meta-analysis was limited by significant heterogeneity among studies and a relatively high prevalence of elevated factor VIII, which may represent an inherited disorder or may be acquired. The prevalence of most other IT traits in the meta-analysis was low and their associations with CVC-related VTE were relatively weak. The available evidence is insufﬁcient to support routinely performing IT testing to inform management decisions in children with CVC-related VTE. (See "Screening for inherited thrombophilia in children", section on 'First episode of CVC-related VTE'.)
Investigational reversal agent for factor Xa inhibitors (September 2016)
Andexanet alfa is an investigational reversal agent for anticoagulants that inhibit factor Xa, including the oral direct factor Xa inhibitors, low molecular weight heparins, and fondaparinux. It is a catalytically inactive form of factor Xa that is administered intravenously as a bolus followed by a two-hour infusion. A recent preliminary report from a study in patients with factor Xa inhibitor-associated major bleeding (ANNEXA-4) has now demonstrated efficacy of andexanet, with excellent or good hemostasis in 37 of 47 patients and reduced anti-factor Xa activity for several hours . Potential concerns include a possible increased risk of thrombosis, although most patients in the study were elderly, had atrial fibrillation and/or risk factors for venous thromboembolism, and were not receiving anticoagulation at the time they developed a thrombus. ANNEXA-4 is ongoing; andexanet is not yet available for clinical or compassionate use. (See "Management of bleeding in patients receiving direct oral anticoagulants", section on 'Antidotes under development'.)
Dosing of direct oral anticoagulants in obese patients (June 2016)
Limited data are available to guide dosing of direct oral anticoagulants (DOACs; dabigatran, apixaban, edoxaban, rivaroxaban) in patients with obesity. The International Society of Thrombosis and Hemostasis (ISTH) has issued guidance on this subject . The major recommendations include use of DOACs at standard doses for those with a body mass index (BMI) ≤40 kg/m2 or weight <120 kg, and avoidance of DOACs in individuals with a BMI >40 kg/m2 or weight ≥120 kg. (See "Direct oral anticoagulants: Dosing and adverse effects".)
Risk of inhibitors in hemophilia A (June 2016)
Individuals with hemophilia who receive coagulation factor infusions are at risk of developing an autoantibody to the factor (a factor inhibitor); this occurs in approximately 25 to 30 percent of individuals with severe hemophilia A. The SIPPET trial (Survey of Inhibitors in Plasma-Product Exposed Toddlers) is the first randomized trial to evaluate the risk of inhibitors with recombinant versus plasma-derived factor VIII products . In SIPPET, 264 children who required factor VIII infusions were randomly assigned to receive a recombinant or a plasma-derived product. Inhibitors were seen more frequently with the recombinant products (37 versus 23 percent). The mechanism of this difference is unknown; the presence of von Willebrand factor in the plasma-derived products or the use of non-human cell lines to produce the recombinant products has been suggested. These results may not apply to recombinant products made in human cell lines or those engineered to have extended half-lives. (See "Factor VIII and factor IX inhibitors in patients with hemophilia", section on 'Recombinant versus plasma-derived products'.)
Investigational laboratory assay for multiple anticoagulants (June 2016)
The prothrombin time (PT) with international normalized ratio (INR) and the activated partial thromboplastin time (aPTT) are used to monitor warfarin and heparin therapy, but these tests are not adequate for assessing the presence or therapeutic effect of direct thrombin inhibitors or direct factor Xa inhibitors. A modified form of the PT that uses highly diluted thromboplastin, designated dFiix-PT, has been developed . In a preliminary study, this assay was able to detect and quantify unfractionated and low molecular weight heparins, vitamin K antagonists, and direct oral anticoagulants. If validated, this test could potentially greatly simplify anticoagulant testing. (See "Clinical use of coagulation tests", section on 'Prothrombin time (PT) and INR'.)
Role of platelet transfusions in bleeding associated with antiplatelet agents (May 2016)
The role of platelet transfusion in patients with antiplatelet agent-associated bleeding has been unclear. A recent randomized trial compared platelet transfusions with standard care in 190 individuals with intracerebral hemorrhage (ICH) in the setting of aspirin or other antiplatelet agents . Compared with those assigned to standard care, individuals who received platelet transfusions had a higher rate of a composite endpoint of death or lower score on the modified Rankin Scale for functional independence. When analyzed separately, the increase in mortality did not reach statistical significance. Serious adverse events were more frequent in the platelet transfusion arm, and ICH enlargement was similar in both arms at approximately 15 percent. Despite these results, such cases can be complex, and we continue to favor an individualized approach. (See "Clinical and laboratory aspects of platelet transfusion therapy", section on 'Platelet function defects'.)
Long-acting factor IX for hemophilia B (May 2016)
Long-acting clotting factor products are appealing for replacement therapy in individuals with hemophilia because they can reduce the frequency of injections. A long-lasting recombinant factor IX-albumin fusion protein (rIX-FP) was approved by the US Food and Drug Administration in 2016 for prophylaxis or treatment of bleeding in individuals with hemophilia B . The half-life is five to sixfold longer than unmodified factor IX products. (See "Treatment of hemophilia", section on 'Longer lasting products'.)
New investigational approach to treating hemophilia A (May 2016)
The mainstay of treatment for hemophilia A is replacement with exogenous factor VIII, which interacts with factor IX to activate factor X in the coagulation cascade. In a new approach, investigators have created a monoclonal antibody (emicizumab; ACE910) that binds simultaneously to factors IX and X, bringing them together and bypassing the role of factor VIII. In a study involving 18 individuals with hemophilia A who had bleeding despite prophylactic or on-demand therapy, once-weekly subcutaneous administration of emicizumab markedly decreased bleeding rates; 11 of these individuals had factor VIII inhibitors . There were no serious adverse events or thrombotic complications. Additional studies are ongoing. (See "Treatment of hemophilia", section on 'Novel proteins')
LYMPHOMA: HODGKIN AND NON-HODGKIN
Acquired C1 inhibitor deficiency in lymphoma patients (August 2016)
Acquired C1 inhibitor deficiency is a rare disorder that causes episodes of angioedema that are unresponsive to epinephrine or antihistamines and can be fatal if the airway is compromised. In previous series of patients with acquired angioedema, 30 to 40 percent were found to have a malignancy of some type, most commonly a non-Hodgkin lymphoma (NHL). However, the overall prevalence of acquired C1 inhibitor deficiency in patients with lymphoma was unknown. In a new retrospective study of 131 patients with different types of lymphoma, patients were screened at the time of lymphoma diagnosis for deficiency and dysfunction of C1 inhibitor . Four patients (3 percent) were symptomatic with episodic swelling and all four had both functional tests and levels of C1 inhibitor that were below 50 percent of normal. Three of these four had splenic marginal cell lymphoma. Another 10 patients had abnormal C1 inhibitor function but had not developed angioedema. This study provides an initial estimate of the prevalence of acquired C1 inhibitor deficiency in lymphoma patients and suggests that those with splenic marginal cell lymphoma may be at particular risk. (See "Acquired C1 inhibitor deficiency: Clinical manifestations, epidemiology, pathogenesis, and diagnosis", section on 'Lymphoproliferative disorders and B cell malignancies'.)
PET/CT-adapted therapy in advanced Hodgkin lymphoma (June 2016)
Mid-treatment positron emission tomography/computed tomography (PET/CT) has prognostic value in patients with Hodgkin lymphoma (HL), and initial studies suggest that treatment may be safely deescalated in early responders. In a large trial, 935 patients with advanced-stage HL who achieved a "negative" PET/CT after two cycles of combination chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) were randomly assigned to receive four more cycles of ABVD or four cycles of doxorubicin, vinblastine, and dacarbazine (AVD) . AVD and ABVD resulted in similar rates of progression-free survival at three years (PFS, 84 versus 86 percent), although the 95% confidence intervals included a decrease in PFS with AVD of 5.3 percent. Decisions for an individual patient must take into account the risk of pulmonary toxicity with further bleomycin versus a potentially small increase in relapse with bleomycin omission. Omission in those with a "negative" PET/CT is most attractive for patients with additional risk factors for bleomycin toxicity (eg, older age, underlying pulmonary disease, active smokers). Application of this approach must pay careful attention to the methodology used including the timing of PET/CT and cutoff values used to determine "negative" scans. (See "Initial treatment of advanced (stage III-IV) classical Hodgkin lymphoma", section on 'Response adapted therapy'.)
Maintenance rituximab after bendamustine plus rituximab in mantle cell lymphoma (June 2016)
Maintenance rituximab improves progression-free survival (PFS) and may improve overall survival in patients with mantle cell lymphoma (MCL) treated with R-CHOP induction, but its role after induction with bendamustine plus rituximab (BR) is not well understood. In a preliminary report, presented in abstract form, a randomized phase 2 trial comparing two years of maintenance rituximab versus observation in 168 patients with newly diagnosed MCL treated with BR induction showed no significant difference in PFS at a median follow-up of 59 months (HR 0.71; 95% CI 0.41-1.23; median 55 versus 72 months) . For patients with newly diagnosed MCL who have had at least a partial response to initial therapy and are not eligible for autologous hematopoietic cell transplantation (HCT), the decision to use maintenance rituximab must take into account the initial therapy administered. Given the lack of a PFS benefit in this randomized trial, we suggest observation rather than maintenance following BR induction. In contrast, for those receiving R-CHOP induction, we suggest the use of maintenance rituximab until progression, rather than observation with treatment at the time of progression. (See "Initial treatment of mantle cell lymphoma", section on 'Maintenance therapy'.)
R-CHOP/R-DHAP for mantle cell lymphoma (June 2016)
Nonrandomized prospective trials have suggested high rates of deep responses in patients with mantle cell lymphoma (MCL) treated with alternating cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) followed by autologous hematopoietic cell transplantation (HCT). A randomized trial in 497 younger adults with previously untreated MCL compared six cycles of this regimen versus six cycles of R-CHOP, both followed by autologous HCT . After a median follow-up of six years, R-CHOP/R-DHAP resulted in longer time to treatment failure (median nine versus four years), but this has yet to translate into a statistically significant survival benefit (HR 0.78; 95% CI 0.57-1.07). R-CHOP/R-DHAP was associated with higher rates of hematologic toxicity, febrile neutropenia, and renal toxicity. We do not routinely use R-CHOP/R-DHAP due to toxicity concerns and lack of a proven survival benefit. (See "Initial treatment of mantle cell lymphoma", section on 'Conventional chemoimmunotherapy'.)
Nivolumab for Hodgkin lymphoma (May 2016)
Patients with Hodgkin lymphoma (HL) that has relapsed or progressed following autologous hematopoietic cell transplantation (HCT) and post-transplantation brentuximab vedotin have limited treatment options. Initial data from two prospective studies have reported high response rates with the programmed death 1 (PD-1) inhibitor nivolumab, which has been beneficial in the treatment of melanoma. Based on this, the US Food and Drug Administration has approved the use of nivolumab in this patient population . Serious adverse effects seen in this population include those reported in patients with melanoma (pneumonitis, colitis, hepatitis, nephritis, renal dysfunction, and thyroid dysfunction). In addition, patients treated with nivolumab who proceed to allogeneic HCT have a high rate of transplant-related complications such as hyperacute graft-versus-host disease (GVHD), severe acute GVHD, steroid-requiring febrile syndrome, and hepatic sinusoidal obstruction syndrome. Further study is needed to see if these high response rates translate into a survival benefit and to clarify the role of this agent in the treatment of multiply relapsed HL. (See "Second and third line chemotherapy regimens and biologic therapy for relapsing or resistant classical Hodgkin lymphoma", section on 'PD-1 blockade'.)
Rituximab in Burkitt lymphoma (April 2016)
Rituximab is an attractive addition to conventional chemotherapy for Burkitt lymphoma (BL) given its efficacy in other CD20-positive non-Hodgkin lymphoma subtypes, the expression of CD20 in most cases, and the results of several uncontrolled, prospective trials which suggested improved outcomes with rituximab. In a multicenter, open-label trial, 260 adults with previously untreated HIV-negative BL were randomly assigned to receive dose-dense chemotherapy with or without rituximab . After a median follow-up of 38 months, the addition of rituximab improved event-free and overall survival without increased toxicity. These results provide stronger evidence to support the use of rituximab in BL. To lessen the risk of tumor lysis syndrome, we wait until the second cycle of chemotherapy before incorporating rituximab into the treatment program. (See "Treatment of Burkitt leukemia/lymphoma in adults", section on 'Incorporation of rituximab'.)
MULTIPLE MYELOMA AND OTHER PLASMA CELL DISORDERS
Daratumumab-based regimens in relapsed multiple myeloma (October 2016, Modified October 2016)
Two recent multicenter randomized trials including over 1000 patients have demonstrated large improvements in progression-free survival (PFS) when the anti-CD38 monoclonal antibody daratumumab is added to standard regimens in relapsed multiple myeloma. The addition of daratumumab to either lenalidomide plus dexamethasone (POLLUX trial) or to bortezomib plus dexamethasone (CASTOR trial) resulted in substantially improved response rates and PFS with a mild to moderate increase in toxicity [23,24]. Mostly mild infusion reactions were common with the first infusion, but rarely resulted in drug discontinuation. Overall survival data are not yet mature. Based on these results we now recommend a daratumumab-based regimen for the treatment of first relapse in myeloma. (See "Treatment of relapsed or refractory multiple myeloma", section on 'Daratumumab'.)
Restrictive postoperative transfusion strategy in infants and children with congenital heart disease (October 2016)
In a randomized trial of restrictive versus liberal postoperative transfusion strategies in 162 infants with congenital heart disease undergoing surgical repair or palliation, a restrictive transfusion strategy reduced the red cell transfusion rate, without increasing in-hospital mortality, need for extracorporeal membrane oxygenation (ECMO) support, or hospital length of stay . The restrictive group was transfused for hemoglobin <7.0 g/dL for biventricular repairs or <9.0 g/dL for palliative procedures plus a clinical indication; the liberal group was transfused for hemoglobin <9.5 g/dL for biventricular repairs or <12 g/dL for palliative procedures. Larger more definitive trials are needed before clear transfusion guidelines in this population can be made. (See "Red blood cell transfusion in infants and children: Indications", section on 'Surgery'.)
Laboratory testing of donated blood for Zika virus (April 2016, Modified August 2016)
The US Food and Drug Administration (FDA) now recommends universal testing of blood components for Zika virus in the United States and its territories (with a several month implementation period), based on an increasing number of cases of mosquito-borne transmission of Zika virus in Florida and Puerto Rico and the potential for sexual transmission from asymptomatic individuals . The testing involves one of two assays that detect Zika virus RNA. Approximately 1 percent of donations from Puerto Rico, an active transmission area, were positive for Zika virus in June of 2016 . Blood collection facilities also use the donor medical and travel history to disqualify individuals who may be infected with Zika virus. (See "Blood donor screening: Laboratory testing", section on 'Zika virus'.)
Reducing transmission of malaria by blood transfusion using a pathogen inactivation technology (May 2016)
Pathogen inactivation technologies are treatments that can be applied to blood products before they are transfused, to reduce transmission of viable infectious agents. In Ghana, where malaria is endemic and testing of donated blood for parasitemia is not routinely available, a randomized trial demonstrated that treatment of whole blood with one of these methods (riboflavin [vitamin B2] plus ultraviolet [UV] light) was able to significantly reduce transfusion-transmitted malaria . (See "Pathogen inactivation of blood products", section on 'Potential benefits'.)
Thrombotic microangiopathy from interferon (October 2016)
Drug-induced thrombotic microangiopathy (DITMA) has been described with a number of chemotherapeutic, immunosuppressive, and other drugs. Unlike thrombotic thrombocytopenic purpura (TTP), DITMA is not associated with severely reduced ADAMTS13 activity, and the principal treatment is drug discontinuation rather than plasma exchange. A new report has provided strong evidence for interferon as a cause of TMA . Patients receiving interferon who develop signs of a TMA should have the drug discontinued promptly before organ failure develops. (See "Drug-induced thrombotic microangiopathy", section on 'Immunosuppressive agents'.)
Complement-mediated HUS, eculizumab, meningococcal group B vaccine, and risk for hemolytic anemia (September 2016)
The introduction of eculizumab (a monoclonal antibody that blocks activation of the terminal complement cascade) has significantly improved the outcome of patients with complement-mediated hemolytic uremic syndrome (HUS), a rare, potentially life-threatening disease. Eculizumab therapy increases the risk of meningococcal infection, and vaccination against Neisseria meningitidis (with a quadrivalent vaccine and, for patients older than 10 years, a serogroup B vaccine) has been recommended in treated patients. However, a review from Health Canada reported an increased risk of hemolytic anemia following receipt of the multicomponent meningococcal serogroup B vaccine (Bexsero, MenB-4C) among patients who were already being treated with eculizumab . To minimize the risk of hemolysis, serogroup B meningococcal vaccination should be performed prior to the initiation of eculizumab therapy, if possible. In cases where prior vaccination is not possible, the manufacturer of eculizumab recommends that serogroup B meningococcal vaccination should be administered when patients are stable and their disease is well controlled and it is assumed that the blood level of eculizumab is high. (See "Complement-mediated hemolytic uremic syndrome", section on 'Adverse effects'.)
Defects in von Willebrand factor function following transcatheter aortic valve replacement (August 2016)
Postprocedural aortic regurgitation (largely paravalvular) develops in approximately 10 to 20 percent of patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR) and is associated with worse outcomes, including an increased mortality rate at one year. A study of patients with aortic stenosis undergoing TAVR identified an association between presence of more than mild postprocedural aortic regurgitation and defects in von Willebrand factor function following TAVR . Defects in von Willebrand factor function following TAVR were also associated with mortality risk at one year. While these findings are intriguing, further data are needed to determine the utility of von Willebrand factor testing in patients undergoing TAVR. (See "Transcatheter aortic valve replacement: Overview of complications", section on 'Paravalvular regurgitation'.)
Danazol in telomere disorders (May 2016)
Telomeres are regions at the ends of chromosomes that maintain chromosomal integrity. Telomeres shorten with normal aging, but inherited disorders of premature telomere shortening can cause aplastic anemia (AA), pulmonary fibrosis, and certain malignancies. To date, no therapies have been developed to reverse premature telomere shortening. In the first prospective study to evaluate androgen therapy for telomere disorders, the androgen danazol was administered to 27 individuals with mutations that affect telomere length (most with AA) . Danazol was associated with improved hematologic parameters in those with cytopenias, stabilization of pulmonary status in those with pulmonary fibrosis, and reduced telomere shortening in all evaluable participants. Androgens are an attractive candidate for treating telomere disorders, although further study is needed. (See "Aplastic anemia: Pathogenesis; clinical manifestations; and diagnosis", section on 'Telomerase mutations and telomere length' and "Pathogenesis of idiopathic pulmonary fibrosis", section on 'Genetic predisposition'.)
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