- Late presentation of dyskeratosis congenita. British journal of haematology 2019
World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management.
American journal of hematology
The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary, clonal) disorders with potential for end-organ damage.Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1.5 x 109 /L and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of morphologic review of the blood and marrow, standard cytogenetics, fluorescent in situ-hybridization, flow immunophenotyping, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm.Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes which includes the major category 'myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2', and the MPN subtype, chronic eosinophilic leukemia, not otherwise specified' (CEL, NOS). Lymphocyte-variant hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (e.g. < 1.5 x 109 /L) without symptoms or signs of organ involvement, a watch and wait approach with close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES. Hydroxyurea and interferon-alfa have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL with outcomes reported for limited numbers of patients. The use of antibodies against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), as well as other targets on eosinophils remains an active area of investigation. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ajh.25617
View details for PubMedID 31423623
A Kindred with a β-Globin Base Substitution [β89(F5)Ser→Arg (AGT>AGG); HBB: c.270T>G] Resulting in Hemoglobin Vanderbilt.
High oxygen affinity hemoglobins (Hbs), characterized by a decreased ability to release oxygen to the tissues and a left-shifted oxygen dissociation curve, are a rare cause of secondary erythrocytosis. Here, we report a base substitution in the β-globin gene at codon 89 (AGT>AGG) in a kindred with familial erythrocytosis resulting in Hb Vanderbilt, a high oxygen affinity variant.
View details for DOI 10.1080/03630269.2019.1680382
View details for PubMedID 31657650
The new tool "KIT" in advanced systemic mastocytosis.
Hematology. American Society of Hematology. Education Program
2018; 2018 (1): 127–36
Mastocytosis is a rare disease characterized by KIT-driven expansion and accumulation of neoplastic mast cells in various tissues. Although mediator symptoms related to mast cell activation can impose a symptom burden in cutaneous disease and across the spectrum of systemic mastocytosis subtypes, the presence of an associated hematologic neoplasm and/or organ damage denotes advanced disease and the potential for increased morbidity and mortality. In addition to the revised 2016 World Health Organization classification of mastocytosis, a new diagnostic and treatment toolkit, tethered to enhanced molecular characterization and monitoring, is poised to transform the management of patients with advanced systemic mastocytosis (advSM). Although the efficacy of midostaurin and novel selective KIT D816V inhibitors, such as avapritinib (BLU-285), have validated KIT as a therapeutic target, the clinical and biologic heterogeneity of advSM requires that we reimagine the blueprint for tackling these diseases and use tools that move beyond KIT-centric approaches.
View details for PubMedID 30504301
Myelophthisic marrow involved by breast cancer and acute myeloid leukemia
2018; 131 (9): 1036
View details for PubMedID 29496704
- Concurrent uvulitis and epiglottitis. Cleveland Clinic journal of medicine 2016; 83 (10): 712-714
- Safe and effective use of ponatinib in a patient with chronic myeloid leukemia and acute venous thromboembolism on therapeutic anti-coagulation LEUKEMIA & LYMPHOMA 2016; 57 (1): 193-195
- Gastric Pneumatosis: An Unexpected Complication of Intractable Vomiting in Gastrointestinal Cancers JOURNAL OF PAIN AND SYMPTOM MANAGEMENT 2015; 49 (4): E3-E4
The Utility of Proadrenomedullin and Procalcitonin in Comparison to C-Reactive Protein as Predictors of Sepsis and Bloodstream Infections in Critically III Patients With Cancer
CRITICAL CARE MEDICINE
2014; 42 (12): 2500-2507
Infections in critically ill patients continue to impose diagnostic and therapeutic challenges. We seek to investigate the utility of proadrenomedullin and procalcitonin as diagnostic and prognostic biomarkers in febrile critically ill patients with cancer and compare their performance with that of C-reactive protein.Single-center prospective cohort study.Tertiary care, academic, university hospital.One hundred fourteen critically ill patients with cancer with fever.None.Blood samples were withdrawn on the day of fever onset and 4 to 7 days thereafter, and the serum proadrenomedullin, procalcitonin, and C-reactive protein levels were measured using the Kryptor technology afterward. Of the 114 adult patients, 27 had bloodstream infections, 36 had localized infections, and the remaining had no infections. The area under the receiver operating characteristic curve for bloodstream infection diagnosis was significantly greater for proadrenomedullin (0.70; 95% CI, 0.59-0.82) and procalcitonin (0.71; 95% CI, 0.60-0.83) compared with C-reactive protein (0.53; 95% CI, 0.39-0.66) (p = 0.021 and p = 0.003, respectively). Receiver operating characteristic analysis also showed that proadrenomedullin (p = 0.005) and procalcitonin (p = 0.009) each had a better performance than C-reactive protein in predicting patients' mortality within 2 months after their fever onset. Regarding patients' response to antimicrobial therapy, proadrenomedullin, procalcitonin, and C-reactive protein levels all significantly decreased from baseline to follow-up in responders (p ≤ 0.002), whereas only proadrenomedullin level significantly increased in nonresponders (p < 0.0001). In patients with documented infections, proadrenomedullin (0.81; 95% CI, 0.71-0.92) and procalcitonin (0.73; 95% CI, 0.60-0.85) each had a greater area under the curve compared with C-reactive protein (0.59; 95% CI, 0.45-0.73) as for as predicting response (p = 0.004 and p = 0.043, respectively). However, for all febrile patients, proadrenomedullin had a significantly greater area under the curve for predicting favorable response than procalcitonin (p < 0.0001).In critically ill patients with cancer, proadrenomedullin and procalcitonin both have a promising role in predicting bloodstream infections in a manner more helpful than C-reactive protein. These two biomarkers were superior to C-reactive protein in the prognostic analysis of response to antimicrobial therapy for those patients with documented infections. However, proadrenomedullin was superior to procalcitonin in predicting response in all febrile patients and was unique in showing increased levels among nonresponders.
View details for DOI 10.1097/CCM.0000000000000526
View details for Web of Science ID 000345255900005
View details for PubMedID 25083975
Granulocyte transfusions in hematologic malignancy patients with invasive pulmonary aspergillosis: outcomes and complications
ANNALS OF ONCOLOGY
2013; 24 (7): 1873-1879
Granulocyte transfusions (GTXs) have been used successfully as an adjunctive treatment option for invasive infections in some neutropenic patients with underlying hematologic malignancy (HM).We sought to determine the impact of GTX as an adjunct to antifungal therapy in 128 patients with HM and prolonged neutropenia (≥14 days) with a proven or probable invasive aspergillosis (IA) infection by retrospectively reviewing our institutional database.Fifty-three patients received GTX and 75 did not. By univariate analysis, patients with invasive pulmonary aspergillosis who received GTX were less likely to respond to antifungal therapy (P = 0.03), and more likely to die of IA (P = 0.009) when compared with the non-GTX group. Among patients who received GTX, 53% developed a pulmonary reaction. Furthermore, IA-related death was associated with the number of GTX given (P = 0.018) and the early initiation of GTX within 7 days after starting antifungal therapy (P = 0.001). By multivariate competing risk analysis, patients who received GTX were more likely to die of IA than patients who did not receive GTX (P = 0.011).Our study suggests that GTX does not improve response to antifungal therapy and is associated with worse outcomes of IA infection in HM patients, particularly those with pulmonary involvement.
View details for DOI 10.1093/annonc/mdt110
View details for Web of Science ID 000321881600024
View details for PubMedID 23519997
View details for PubMedCentralID PMC4990830
Can procalcitonin differentiate Staphylococcus aureus from coagulase-negative staphylococci in clustered gram-positive bacteremia?
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE
2013; 76 (2): 158-161
Procalcitonin (PCT) and pro-adrenomedullin (ProADM) have been proposed as diagnostic and prognostic biomarkers of infection. Between July 2009 and January 2012, we studied the role of these biomarkers in 163 patients with clustered gram-positive and gram-negative bacteremia. PCT levels were significantly higher in patients with Staphylococcus aureus and gram-negative bacteremia than those with coagulase-negative staphylococci (CoNS) isolated from blood cultures (P = 0.29 and <0.001, respectively). ProADM levels were only significantly higher in patients with gram-negative bacteremia (median 1.46 nmol/L) than those with CoNS (median 1.01 nmol/L) (P = 0.04). Among patients with CoNS, PCT, and ProADM, levels failed to differentiate blood contamination (medians 0.24 ng/mL and 0.97 nmol/L) from true bacteremia (medians 0.26 ng/mL and 1.14 nmol/L) (P = 0.51 and 0.57, respectively). In cancer patients, PCT (and to a lesser extent, ProADM) was useful in differentiating CoNS from S. aureus and gram-negative bacteremia.
View details for DOI 10.1016/j.diagmicrobio.2013.03.004
View details for Web of Science ID 000319717500008
View details for PubMedID 23578976
Pro-adrenomedullin as a Novel Biomarker for Predicting Infections and Response to Antimicrobials in Febrile Patients With Hematologic Malignancies
CLINICAL INFECTIOUS DISEASES
2013; 56 (7): 943-950
Health professionals and researchers have become increasingly interested in biomarkers that help them in diagnosis of infections with recent growing attention to procalcitonin (PCT) and pro-adrenomedullin (proADM).This study compares proADM to PCT as diagnostic and prognostic biomarkers of infection in febrile patients with hematologic malignancies (HMs). From June 2009 to December 2010, 340 febrile HM patients were evaluated for presence of sepsis, systemic inflammatory response syndrome (SIRS), documented infections, and response to antimicrobial therapy.ProADM and PCT levels were measured at onset of fever and then on days 4-7 afterward. Of the 340 patients, 103 had definite sepsis, and 159 had SIRS. Only proADM initial levels were significantly higher in patients with localized bacterial infections than in those with no documented infection (P = .019) and in patients with definite sepsis than those with SIRS (P = .023). The initial proADM and PCT levels were significantly higher in neutropenic patients with BSIs than in those without documented infections (P = .010 and P = . 011, respectively). Follow-up, proADM, and PCT levels decreased significantly in response to antimicrobial therapy in patients with bacterial infections (BSIs or localized; P = .007 and P = .002, respectively).ProADM and PCT have promising roles in assisting clinicians in managing febrile HM patients. However, proADM appears to have the advantage of predicting localized bacterial infection and differentiating sepsis from SIRS.
View details for DOI 10.1093/cid/cis1029
View details for Web of Science ID 000316167000008
View details for PubMedID 23288950
Nephrostomy Tube Related Pyelonephritis in Patients with Cancer: Epidemiology, Infection Rate and Risk Factors
JOURNAL OF UROLOGY
2013; 189 (1): 130-135
Nephrostomy tube placement is often necessary to avert acute renal failure in patients with cancer with obstructive uropathy or in patients with ureteral leak. However, there have been limited published studies on the rate and risk of nephrostomy tube related pyelonephritis in patients with cancer. Therefore, in this study we determined rates of nephrostomy tube related pyelonephritis and predisposing risk factors in patients with cancer.We retrospectively reviewed patients who underwent nephrostomy tube placement between September 1, 2009 and September 16, 2010 at MD Anderson Cancer Center. Patients were followed for 90 days. The primary outcome assessed was the development of nephrostomy tube related pyelonephritis and the secondary outcome was the development of asymptomatic bacteriuria. We also determined risk factors associated with pyelonephritis.Of the 200 patients analyzed 38 (19%) had pyelonephritis and 15 (7.5%) had asymptomatic bacteriuria. Of the nephrostomy tube related infections 34 cases (89%) were with the primary nephrostomy tube. Subsequently 4 of the patients who underwent nephrostomy tube exchange had an episode of pyelonephritis. Pyelonephritis developed within the first month in 19 (10%) patients. Prior urinary tract infection and neutropenia were found to be significant risk factors for pyelonephritis (p = 0.047 and 0.03, respectively).The placement of nephrostomy tubes in patients with cancer is associated with a significant rate of pyelonephritis. Neutropenia and history of urinary tract infection were significant risk factors for pyelonephritis. This finding warrants further investigation into preventive strategies to reduce the infection rate.
View details for DOI 10.1016/j.juro.2012.08.094
View details for Web of Science ID 000312604800044
View details for PubMedID 23164390
Can procalcitonin distinguish infectious fever from tumor-related fever in non-neutropenic cancer patients?
2012; 118 (23): 5823-5829
Procalcitonin (PCT) has been proposed as a marker of infection and was studied in neutropenic patients. This study investigated its role in non-neutropenic febrile cancer patients (NNCPs).Between July 2009 and July 2010, a total of 248 NNCPs with fever were studied. PCT was measured in plasma within 24 hours of fever onset and 4 to 7 days thereafter, using a Kryptor system with a lower limit of quantitation of 0.075 ng/mL. Patients' clinical, microbiological, and radiological data were reviewed to make the diagnosis and were correlated with PCT levels.This study included 30 patients with bloodstream infection (BSI), 60 with localized bacterial infection, 141 with no documented infection, and 8 with tumor-related fever. Most patients (98%) were inpatients or admitted to the hospital during the study. Patients with BSI had significantly higher PCT levels than did those with documented localized infections (P = .048) and no documented infection (P = .011). PCT levels were significantly higher in septic patients than in those without sepsis (P = .012). Patients with stage IV disease or metastasis had significantly higher baseline PCT levels than did those with early stages of cancer (P < .05). PCT levels dropped significantly in patients with bacterial infections in response to antibiotics (P < .0001).Baseline PCT levels are predictive of BSI and sepsis in NNCPs. They may be predictors of metastasis and advanced cancer. Subsequent decrease in PCT levels in response to antibiotics is suggestive of bacterial infection. Larger trials are needed to confirm the results of this pilot study.
View details for DOI 10.1002/cncr.27602
View details for Web of Science ID 000311306000014
View details for PubMedID 22605389
Anomalous Inferior Vena Cava Drainage to the Left Atrium With Successful Staged Repair in a 32-Year-Old Woman With Arthritis
2010; 31 (6): 912-914
This report describes a case involving anomalous drainage of inferior vena cava (IVC) to the left atrium diagnosed when the patient was 32 years old. The tricuspid valve and the right ventricle were small. Successful surgical repair was performed, with significant improvement of the patient's clinical status. The use of exercise testing with pulse oxymetry monitoring aided in the decision of timing for closure of the iatrogenically created atrial septal defect.
View details for DOI 10.1007/s00246-010-9738-1
View details for Web of Science ID 000280405600031
View details for PubMedID 20544188