Renal dysfunction in sickle cell disease is not only a chronic comorbidity but also a mortality risk factor. Though renal dysfunction starts early in life in sickle cell patients, the predictors that can identify sickle cell disease patients at risk for developing renal dysfunction is not known. We used the Truven Health MarketScan Medicaid Databases from 2007–2012. Incidence of new acute renal failure (ARF) and chronic kidney disease (CKD) was calculated in this cohort. There were 9481 patients with a diagnosis of sickle cell disease accounting for 64,201 hospital admissions, during the study period. Both ARF and CKD were associated with higher risk of inpatient mortality, longer duration of the hospital stay and expensive hospitalizations. The yearly incidence of new ARF in sickle cell disease patients was 1.4% and annual CKD incidence was 1.3%. The annual rate of new ARF and CKD in the control group was 0.4 and 0.6%, respectively. The most important predictors of new CKD were proteinuria, ARF and hypertension. Chronic kidney disease, hypertension and sickle cell crisis were the most important predictors of new ARF. The annual rate of incidences of ARF and CKD were 2- to 3-fold higher in sickle cell disease compared to the non sickle cell disease group. Besides the common risk factors for renal disease in the general population, it is imperative to monitor the sickle cell disease patients with more severe disease to prevent them from developing renal dysfunction.
Kaposi Sarcoma (KS) is the most common malignancy associated with Acquired Immune Deficiency Syndrome (AIDS) and is caused by Human Herpesvirus 8 (HHV 8) or Kaposi Sarcoma Herpesvirus (KSHV). In about 90% of cases Kaposi Sarcoma is associated with cutaneous lesions; however visceral disease can occur in the absence of cutaneous involvement. In the era of Highly Active Antiretroviral Therapy (HAART), the incidence of KS has declined. Clinical features of pulmonary KS might be difficult to distinguish from pneumonia in the immunocompromised patients and could lead to diagnostic challenges. First-line treatment of KS is with HAART and the incidence has declined with its use. Systemic chemotherapy may play a role depending on the extent of the disease. We report the case of a young man who presented with pulmonary symptoms and was later found to have pulmonary KS. Interestingly this diagnosis was made in the absence of the classic skin lesions. His disease was complicated by progressive respiratory failure and he eventually died.
PURPOSE: Inferior outcomes of Black patients with lung cancer compared with other racial groups are often linked to socioeconomic factors. It is crucial to determine whether a varying prevalence of targetable mutations limits treatments and contributes to disparities. MATERIALS AND METHODS: We conducted a meta-analysis on the prevalence of lung cancer EGFR, ALK, ROS-1, and BRAF mutations in Black patients compared with White, Hispanic, and Asian patients. We searched PubMed/MEDLINE, Cochrane Library, EMBASE, CENTRAL, Google Scholar, and clinicaltrials.gov databases. We selected studies reporting the prevalence of at least one mutation in the Black population. We calculated the pooled prevalence of mutations using fixed effects, exact binomial distributions, and Freeman-Turkey double arcsine transformation to stabilize the variances. RESULTS: Twenty studies with 11,867 patients were included. In Black patients, EGFR was the most prevalent mutation (6%; 95% CI, 5 to 7), followed by BRAF (1%; 95% CI, 0 to 2), ALK (1%; 95% CI, 0 to 2), and ROS-1 (0%; 95% CI, 0 to 1). Black patients had a lower prevalence of EGFR mutations than White, Hispanic, and Asian patients ( P < .01). BRAF mutations were less prevalent in Black compared with White patients ( P < .05), and ALK mutations were less prevalent when compared with Hispanic patients ( P < .05). CONCLUSION: EGFR is the most frequent mutation found in Black patients, although its prevalence is lower than that in other races. Black patients have a low overall prevalence of ALK, ROS-1, and BRAF mutations. Given that disproportional eligibility for targeted therapies may be contributing to inferior outcomes, research focused on the Black population is needed to evaluate specific tumor characteristics and therapeutic strategies.
Introduction: Daratumumab is an IgG Kappa monoclonal antibody (mAB) to CD38, a surface glycoprotein expressed on plasma cells. It was approved in 2015 as monotherapy for Multiple Myeloma (MM) patients who failed three prior lines of therapy. Its approval was then expanded to second line and most recently first line. As such, patients are now getting earlier and longer exposure to this mAB. Disease response to daratumumab is monitored by demonstrating a fall in paraprotein levels. It is becoming widely appreciated that hypogammaglobulinemia (HGGE) ie. (IgG<600mg/dl) with risk of infection, is a potential complication for patients on daratumumab. The immune mediated attack by daratumumab on CD38 expressing plasma cells also results in destruction of normal lymphocytes, resulting in impaired production of polyclonal immunoglobulins and diminished immunity. We aim to explore the incidence, severity and clinical significance of HGGE in patients on daratumumab. Methods: We conducted a retrospective chart review of all patients treated with daratumumab as single agent or in combination (November 2015-June 2019), who had documented baseline and post therapy quantitative IgG levels. Demographics, subtype of plasma cell disease, bone marrow cytogenetics/FISH, serial IgG levels, incidence of significant infections and need for IVIG therapy were collected as part of this exploratory data analysis. Results: Among 145 eligible patients, 53% were male, 37% Hispanic, 19% Black/African American and 72% were age<70 at diagnosis. The majority of patients had an IgG paraprotein (56.6%), followed by IgA (18.6%), Free Kappa only (13.1%) and Free Lambda only (9.7%). Hispanics were more likely to have high risk cytogenetics (OR=2.29, p=0.0804). 34.5% of patients had previous autologous stem cell transplant. At baseline 30.3% of all patients had HGGE; 58.1% non-IgG patients and only 9.6% IgG patients. The mean baseline IgG level in IgG patients was 1986.1 mg/dl and for non-IgG patients was 698.1 mg/dl. After being treated with daratumumab, 61.4 % of all patients developed HGGE; 42.2% of IgG patients and 87.1% of non-IgG patients. The mean Nadir IgG level for the IgG subtype cohort was 643.7 mg/dl and for the non-IgG cohort was 355.9 mg/dl. The incidence of significant infection in total group was 23.4% (21.7% in IgG vs 25.8% in non-IgG). Bacterial pneumonia and sepsis were the two most common infections. Despite the relatively high incidence of HGGE in this cohort, only 11 were treated with IVIG. (5 IgG vs 6 non-IgG). Using a univariate logistic regression model, Black/ African Americans and patients with higher baseline IgG were less likely, but non-IgG patients were more likely to develop HGGE (all p<0.05) . Conclusion: Our study identifies a high incidence of meaningful HGGE in patients on daratumumab. In the non-IgG subtype, the relationship is straightforward, as any drop in IgG reflects a drop in polyclonal immunoglobulins and impaired humoral immunity. In contrast, in the IgG subtype, a fall in IgG levels has two components; a fall in the monoclonal protein (indicative of favorable disease response) as well as a fall in polyclonal IgG. There was a lower incidence of pre and post treatment HGGE in the IgG cohort compared to the non-IgG cohort( ie.IgA, IgD, Free Kappa and Free Lambda). In contrast the incidence of infection in both cohorts were very similar. This suggests that polyclonal HGGE in IgG subtype plasma cell disorders may be largely undetected and undertreated, due to apparently normal IgG levels caused by pathologic production of monoclonal IgG. When we attempt to subtract the monoclonal element (m-spike in the serum protein electrophoresis) from the total IgG, the magnitude of hypogammaglobulinemia in the IgG cohort approximates that of the non-IgG group. Given that daratumumab adds a small amount to the measured m-spike, further techniques to quantify true polyclonal IgG levels in the IgG cohort are needed. The incidence and depth of HGGE associated with daratumumab has not been previously well quantified. Our study demonstrates that the incidence of HGGE doubled after therapy with daratumumab (30.3% vs 61.4%). This data will sensitize physicians and possibly lead to generation of guidelines for closer monitoring of IgG, use of IVIG and other precautions in patients on daratumumab. In our own institution, we anticipate the detection of HGGE and use of IVIG in these patients to increase substantially. Disclosures Hoffman: Celgene: Speakers Bureau.
First described by Sir Nicholas Brodie in 1832, Brodie's abscess is a localized subacute or chronic infection of the bone, typically seen in the metaphases of long bones in children and adolescents. The diagnosis can prove to be enigmatic due to absence of clinical signs and symptoms of systemic disease. We report a very interesting case of Brodie's abscess masquerading as sickle cell vasoocclusive crisis in a 20-year-old female with sickle cell disease and review the literature.
Plasma cell leukemia (PCL) is an uncommon neoplasm of plasma cells, with an aggressive clinical course and poor outcome, even with current standard of care. It can occur either de novo (primary PCL) or as a progression of multiple myeloma (MM). This disease has unique diagnostic criteria but certain genetic markers and clinical features may overlap with MM. Due to the low prevalence of PCL, guidelines on its management are extrapolated from the management of MM and based on small retrospective studies and cases reports/series. We present an interesting case of PCL in a middle-aged African-American male, who was diagnosed incidentally after chest wall imaging for an unrelated complaint. The diagnostic approach, management and outcomes of PCL are discussed.
BACKGROUND: Cell derived MPs are small membrane vesicles released during cell activation or apoptosis. They express an inside-out membrane, which exposes the negatively charged phospholipid layer outside, allowing clotting factors to be anchored and generate thrombin. Among various species of MPs, RMP (red cell MPs), PMP (platelet MPs), LMP (leukocytes), EMP (endothelial cells) are of special interest. They play an important role in hemostasis, thromboses, and inflammation. MPs mirror early injury of parent cells and are sensitive early biomarkers of underlying disorders. TTP is a microangiopathy mediated by antibody-induced depletion of ADAMTS13, a von Willebrand factor-cleaving protease. Endothelial injury promotes platelet clumping and formation of platelet rich microthrombi in the microcirculation. Subsequent platelet sequestration leads to impaired microcirculation, thrombocytopenia and red cell fragmentation with a microangiopathic hemolytic anemia. Exchange plasmapheresis (EPP) is the standard therapy. It removes antibodies to ADAMTS13, replacing it with ADAMTS13 rich plasma. It is possible that EPP removes thrombogenic MPs to improve the clinical course of TTP. In this study, we investigated MP profiles in active and remission phase of TTP and the effect of EPP on MP profiles. We also aimed to determine if MP profiles may be a useful measure for monitoring clinical course and tracking progress of therapy. METHODS: A retrospective study was conducted evaluating MP assays in patients with TTP. MP profiles were reviewed in acute and remission phases of TTP. Acute phase was defined as thrombocytopenia, clinical evidence of microangiopathy and hemolytic anemia and low ADAMTS13 activity. Remission was defined as sustained normalization of laboratory parameters and no further microangiopathy for at least one month. Patients were studied longitudinally, with MP assays before and after EPP. EMP were measured by CD31+/CD42b− (EMP31), CD62E+ (EMP62); PMP by CD31+/CD42b+ (PMP42) and CD41+ (PMP41). All were measured in platelet-poor plasma by flow cytometry. All MP data are presented in units of x105/µL. The differences in MP patterns among TTP patients in active and remission phases of disease, as well as the effect of EPP on MP profiles were assessed. RESULTS: Among 20 patients with TTP, 8 (40%) were in acute phase and 12 (60%) in remission. An average of 10.7 EPP were performed. The average platelet count prior to EPP was 50.6x103/µL, which increased to 248 x103/µL following the last EPP. ADAMTS13 activity was generally <10% at the onset. For patients in the acute phase, PMPs were low: PMP41 0.32 (±0.11), PMP42 3.11 (±2.56), but consistently increased following EPP to the point of statistical significance at the last treatment: PMP41 1.26 (±0.71), p=0.005 and PMP42 7.65 (±5.03), p=0.039. Moreover, levels were higher in the remission phase for both PMPs, but only statistically significant for PMP41: 1.39, p=0.034. Conversely, EMP62E was initially elevated on presentation, but declined with successive EPP: 6.07 (±3.02) prior to initiation of EPP to 4.5 (±3.1) upon the last day of EPP. Furthermore, this pattern continued into remission, with EMP62E of 2.72 (±2.11), p=0.009. Similar to the trend in EMP62E, RMP was elevated in the acute phase (25.1 [±18.5]) before steadily declining with EPP (19.65 [±12.53]). This progressive drop in RMP persisted for those in remission phase of TTP 10 (±5.42), p=0.015. DISCUSSION/CONCLUSION: Taken collectively, cell derived MP's were found to reflect disease activity and response to therapy. There was a linear correlation between PMP levels and platelet count. Low PMPs in the acute phase reflects the initial thrombocytopenia characteristic of TTP. When EPP was initiated, the disease improved and there was a rise in PMP which mirrored the rise in platelets. This rise was sustained in the remission phase. Conversely, EMP62E and RMP are increased in acute phase TTP due to endothelial activation, microthrombi deposition and red cell fragmentation. After EPP the disease is quiescent, hence the progressive decline of EMP62E and RMP. These results show promising utility of cell derived MP profiles as a clinical tool to surveil chronic TTP patients and to predict disease relapse at an early stage. After EPP is initiated, change in MP Profiles may be used to monitor response to therapy and determine the appropriate time to wean EPP. Disclosures No relevant conflicts of interest to declare.
Background:Current guidelines do not support the routine use of computed tomography (CT) scan of the head in the diagnostic workup of syncope. There is a lack of research to support whether these guidelines apply to the Black population.Aims:This study aims to evaluate the yield of neuroimaging in the evaluation of Syncope in a predominantly Black patient population and to test whether current guidelines based on studies conducted in other populations hold true in this group.Material and Methods:A retrospective review of records of 151 patients admitted to a University Hospital with Syncope from 2011 to 2014 was performed. Data collected include CT head, magnetic resonance imaging of the brain, magnetic resonance angiogram, electroencephalogram, and orthostatic vital signs. Demographic data, admitting service, and comorbid conditions were identified. Syncope was classified as cardiogenic, orthostatic, vasovagal, situational, or undetermined. Statistical analysis was performed to determine which diagnostic tools were useful in identifying the potential causes of syncope. Data analysis was conducted using the Statistical Analysis System software 9.3 (SAS Institute, Cary, NC) and Statistical Analysis and Graphics (NCSS 9.0.7, Kaysville, UT).Results:One hundred and twenty eight (84.8%) of the patients were Black. The average age was 56.62 ± 18.78 standard deviation and 68.2% (103) were female. One hundred and fourteen patients (75.5%) had a CT brain. Five out of 114 patients had an acute abnormality on CT (4.4%). Only 1 of these 5 patients had an abnormality that was related to syncope. CT brain (P = 0.978) was not found to be predictive of underlying etiology of syncope despite high frequency of use.Conclusions:CT head was not useful in determining the etiology of syncope in a predominantly Black population. Current guidelines and studies conducted in other populations have detected similar findings.
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