Sickle cell disease and coronavirus disease-2019 (COVID-19) infection: a single-center experience.

PURPOSE: Sickle cell disease (SCD) has been found to be associated with an increased risk of hospitalization and death from coronavirus disease-2019 (COVID-19). We sought to study clinical outcomes in patients with SCD and a diagnosis of COVID-19 infection. METHODS: We conducted a retrospective analysis of adult patients (>18 years) with SCD who were diagnosed with COVID-19 infection between 1 March 2020 and 31 March 2021. Data on baseline characteristics and overall outcomes were collected and analyzed using SAS 9.4 for Windows. RESULTS: A total of 51 patients with SCD were diagnosed with COVID-19 infection in the study period, out of which 39.3% were diagnosed and managed in the outpatient setting/emergency room (ER) and 60.3% in the inpatient setting. Disease-modifying therapy such as hydroxyurea did not impact inpatient vs outpatient/ER management (P > 0.05). Only 5.71% (n = 2) required intensive care unit admission and were mechanically ventilated and 3.9% (2 patients) died of complications of COVID-19 infection. CONCLUSION: We identified a lower mortality (3.9%) rate among patients in our cohort in comparison to previous studies and a higher burden of inpatient hospitalizations as compared to outpatient/ER management. Further prospective data are needed to validate these findings. Key messages What is already known on this topic COVID-19 has been shown to have a disproportionately unfavorable impact on African Americans, including longer hospital stays, higher rates of ventilator dependence, and a higher overall mortality rate. Limited data also suggest that sickle cell disease (SCD) is associated with an increased risk of hospitalization and death from COVID-19. What this study adds Our analysis did not show a higher mortality due to COVID-19 in patients with SCD. However, we identified a high burden of inpatient hospitalizations in this population. COVID-19-related outcomes did not improve with the use of disease-modifying therapies. How this study might affect research, practice, or policy These results will aid in decision making for triage of patients with COVID-19 and SCD and ensure the most appropriate use of healthcare resources. Our analysis underscores the need for more robust data to identify patients at higher risk of severe disease and/or mortality, necessitating inpatient hospitalization and aggressive management.

Utility of routine pretreatment evaluation of left ventricular ejection fraction in breast cancer patients receiving anthracyclines.

Anthracycline-based chemotherapy is widely used in the management of breast cancer. Despite the lack of clinical evidence, obtaining prechemotherapy left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition scan is a widely adopted practice throughout the world. We present here the results of a retrospective analysis of breast cancer patients who had LVEF measurements in anticipation of an anthracycline chemotherapy to determine whether predefined cardiac risk factors predicted for poor cardiac function. Retrospective data were analyzed from 482 female breast cancer patients in whom LVEF was measured before starting anthracycline-based chemotherapy. Baseline demographics and multiple risk factors associated with congestive heart failure were collected. Twenty-six possible risk factors for CHF were defined, and the frequency of finding an abnormal LVEF as a function of total risk factors was assessed. Statistical tests include chi-squared and logistic regression analysis. The median age of the study population was 52 years. The original chemotherapy plan was changed in 7 patients (1.45%) based on LVEF findings, all of which had asymptomatic LV dysfunction (LVEF ranging 40%-50%). In 32 patients, despite normal LVEF results, anthracyclines were omitted secondary to prior cardiac issues. In 17 patients where LVEF was reported normal, anthracyclines were skipped based on patient's preference, tumor characteristics, or upstaging of the cancer based on imaging studies. No patient with ≤2 risk factors had an abnormal LVEF (N = 350). The probability of finding an abnormal LVEF in patients without any cardiac risk factors is extremely rare. Skipping baseline LVEF assessment may be an option in some patients with no cardiac risk factors undergoing anthracycline-based chemotherapy.

Histiocytic sarcoma as a secondary malignancy: pathobiology, diagnosis, and treatment.

Histiocytic sarcoma (HS) is an extremely rare non-Langerhans cell disorder with an aggressive course and limited treatment options. Recent advances in molecular/genetic sequencing have suggested a common clonal origin between various hematolymphoid disorders and cases of secondary HS. Deriving conclusions from previously reported cases of HS arising secondarily to certain hematolymphoid disorders, here we have tried to provide insight into the mechanisms influencing this evolution. We also discuss a clinical case of a 72-year-old man with a diagnosis of chronic myeloid leukemia (CML), presenting subsequently with a heterogeneous liver mass positive with a diagnosis of HS. The liver mass showed a retained BCR-ABL1 translocation suggesting clonality between the CML and HS. As seen in our case and other reported cases of HS derived secondarily, the concurrent expression of immunoglobulin heavy (IGH)-/light-chain rearrangements or cytogenetic markers common to the primary malignancy suggests an evolutionary mechanism involving lineage switching that could potentially be influenced by genetic or epigenetic cues which may occur at the level of a progenitor or the malignant cell itself.

Objective Basis for Chronic Pain in Patients with Adult Sickle Cell Disease.

Sickle Cell Disease (SCD) affects approximately 100,000 Americans and due to lack of an organized treatment approach, patients with SCD pose a high economic burden on medical services. The patients with SCD have chronic bone damage from bone marrow infraction and vaso-occulsive events. These bone damages lead to chronic pain in patients with SCD. The inadwquate treatment of chronic pain in adult patients with SCD can lead to pseudo-addictive behavior and also affect their psycho-social life. There are certain barriers to adequate pain management in adult patients with SCD, namely, limited knowledge among the clinicians, inadequate assessment, concerns about addiction, and biases against opioid use. Here by presenting radiographs of patients with adult SCD, we would like to provide objective evidence for the pathologic basis of severe chronic pain in adult patients with SCD.

Rare Cardiac Tumor: Do We Know All About Cardiac Myxofibrosarcoma?

Primary cardiac tumors (PCTs) are less frequent and carry an incidence of 1.38 per 100,000 population per year. Myxofibrosarcomas are reported as one of the rarest forms of cardiac sarcomas, mostly with mesenchymal origin and located in the left atrium. Current research indicates an increase in median survival from 14 months to 36 months following complete resection and chemoradiotherapy. A 55-year-old Caucasian woman was admitted with brief self-resolving episodes of aphasia following migraine headaches for the past few months with associated exertional dyspnea and episodes of hypotension. Examination revealed a right-sided facial droop with cardiac murmur on auscultation. MRI brain was recommended which revealed a non-hemorrhagic infarct and multiple watershed infarcts. A transesophageal echocardiography revealed a large mass of around 5 cm in size located at the posterior wall of the left atrium causing mitral stenosis. The patient was initially managed conservatively and referred to cardiothoracic surgery and underwent a complete surgical resection. The histopathological report indicated the presence of primary cardiac sarcoma, and a postoperative positron emission therapy (PET) scan revealed no other foci of cancer further strengthening evidence of a primary cardiac pathology. This case represents a rare cardiac pathology presenting with non-cardiac symptoms.

Sickle Cell Trait: Is It Always Benign?

Sickle cell disease is a well-known homozygous inherited hemoglobinopathy that causes vaso-occlusive phenomena and chronic hemolysis. Vaso-occlusion results in sickle cell crisis and can eventually lead to complications involving multiple organ systems. However, the heterozygous counterpart, sickle cell trait (SCT) has less clinical significance as these patients are generally asymptomatic. This case series examines three unrelated patients with SCT ranging from the age of 27 to 61 years, who presented with pain in multiple long bones. Hemoglobin electrophoresis confirmed a diagnosis of SCT. Radiographic images of the affected sites showed osteonecrosis (ON). Interventions included pain management and bilateral hip replacement in two of the patients. Historically, vaso-occlusive disease in patients with SCT with no evidence of hemolysis or other hallmark findings of sickle cell disease is rare. There are limited reported cases of ON in SCT patients. Clinicians should explore other hemoglobinopathies not tested on routine hemoglobin electrophoresis and alternative risk factors for ON in these patients.

Extramedullary Multiple Myeloma: A Patient-Focused Review of the Pathogenesis of Bone Marrow Escape.

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells, predominantly in the bone marrow. The presentation of MM in extramedullary tissue, particularly the liver, is uncommon with only a few reported cases in literature. We report a rare and unusual presentation of kappa light chain restricted MM with progression of disease to involve the liver. MM was initially diagnosed on bone marrow biopsy, initially treated with carfilzomib, lenalidomide and dexamethasone, later changed to bortezomib, daratumumab and dexamethasone. There was subsequent progression with a new biopsy-proven myelomatous liver lesion. The patient could not receive high-dose chemotherapy due to multiple co-morbidities and extent of disease and eventually succumbed to her disease rapidly. This article emphasizes the poor prognosis of extramedullary involvement in MM and the pathogenic mechanisms by which it develops. Based on a review of the literature of other cases and case series of solitary or diffuse myeloma involvement in the liver, high-dose chemotherapy in combination with proteasome inhibitors and immunomodulators has the best success rate with less relapse and progressive disease in extramedullary myeloma. Our analysis concluded that the gain of CD44, loss of CD56, loss of very late antigen-4 (VLA-4), imbalance of the chemokine receptor-4-chemokine ligand-12 (CXCR4-CXCL12) axis, metastasis-associated lung adenocarcinoma 1 (MALAT1) upregulation, RAS pathway activation as well as 13q and 17p deletions show an increased propensity of malignant plasma cells to leave the bone marrow and hone in extramedullary sites giving rise to more aggressive extramedullary diseases. Targeted therapeutics such as CD44v-directed therapy and reactivation of p53 to wild-type conformation could potentially be evaluated as treatment options in the future to improve outcomes in this aggressive form of MM, especially in patients with advanced disease and limited treatment options.

The Effect of Payer Status on Survival of Patients With Prostate Cancer.

Background Disparities in access to care and proper treatment can have significant implications in patient survival outcome and mortality. This retrospective study of prostate cancer patients from the National Cancer Database (NCDB) between the years 2004 and 2014 and follow-up to the end of 2015 analyzed such effects that variation in payer status might have on outcome. Methods This study used the data of 696,321 diagnosed prostate cancer patients from the NCDB for the years 2004 to 2014 and follow-up to the end of 2015 to analyze the effect that payer status would have on prostate cancer survival. Multivariable cox regression was used to study the hazard ratios (HRs) of payer status and other variables along with the Charlson Comorbidity Index to analyze their associated increased risk of death. Statistical software SAS 9.4 for Windows was used to analyze the overall survival (OS) of patients on different insurance plans along with variations in prostate-specific antigen (PSA) levels and treatment type. Results When looking at OS, those with private insurance had the greatest overall survivability while those on Medicare were the only ones who reached the median OS. In contrast to those who had private insurance, those who had Medicare, the uninsured, and those with Medicaid demonstrated significantly greater risks of death at 43%, 58%, and 69% increased risk of death, respectively. In addition to payer status, other variables were also significant predictors of OS, including demographic factors (age, race), comorbidities, socioeconomic status (income, education), distance traveled to facility, type of facility, treatment delay, treatment modality, PSA levels at diagnosis, and cancer stage at diagnosis. Conclusion Payer status is intricately linked to a number of other variables that might affect survival. Even after adjustment for a number of these factors, insurance status was shown to have a significant effect on prostate cancer survivorship. In contrast to those who had private insurance, those who had Medicare, the uninsured, and those with Medicaid demonstrated significantly greater risks of death at 43%, 58%, and 69% increased risk of death, respectively. Studies have suggested that those without insurance or on Medicaid are less likely to undergo screening and have worse health-related quality of life, while those on Medicare may be deterred from continuing treatment due to high out-of-pocket costs. However, the complete mechanism behind the improved survivorship of those on private insurance is unclear. The effect of payer status on quality of life may be an interest that needs to be further studied. Further research will be required to provide definite reasons for these observations and mediation analysis of other factors could prove to be valuable.

Hexachlorobenzene, a pollutant in hypothyroidism and reproductive aberrations: a perceptive transgenerational study.

Hexachlorobenzene (HCB), a widespread environmental pollutant, contributes to endocrine disruption resulting in hypothyroidism. We investigated the effect of chronic exposure of HCB to explore the functional interconnection between hypothyroidism and infertility. All observations were made through the F1 and F2 generations. Thyroidectomy was also performed to evaluate the contribution of the thyroid gland in affecting ovarian dysfunction and reproductive aberrations. We confirmed that the preconception exposure of HCB leads to hypothyroidism which was reflected by an increase in the body weight, alteration in the thyroid hormones, and alteration of the lipid profile. Hypothyroid female rats exhibited a poor reproductive profile with altered steroidogenic pathways, altered estrus cyclicity, reduced litter size, and stunted growth. The external supplementation of thyroxine in thyroidectomized animals rescues the reproductive aberrations confirming the protective role of the thyroid gland in reproductive biology. All results highlight the jeopardizing functional connection of the thyroid and ovary due to HCB, leading to serious consequences on upcoming generations.

The curious case of hemoglobin DC disease masquerading as sickle cell anemia.

Hemoglobin D is a relatively rare disease first reported in 1951. We present the first reported case of Hemoglobin DC disease. This is a case of a Hemoglobinopathy with DC disease in a woman with a previous diagnosis of Hemoglobin SC disease. A 19-year-old woman presented to the Adult Hematology clinic at a tertiary care hospital in Northwest Louisiana for transition of care from Pediatric Hematology for a diagnosis of Hemoglobin SC disease diagnosed at the age 4. Historical data suggested no avascular necrosis, acute chest syndrome, and very few episodes of pain crisis. She has never taken hydroxyurea. Laboratory work showed persistently normal hemoglobin and white blood cell counts. All sickle cell preparations in the past were negative. Computerized tomography scan of the abdomen was reviewed and showed a spleen grossly normal in size and appearance. Given the incongruent clinical picture for sickle cell disease, repeat hemoglobinopathy evaluation with Capillary electrophoresis and confirmatory acid electrophoresis (to differentiate hemoglobins that co-migrate with Hemoglobin S) showed a probable double heterozygote for Hemoglobin D and C with suspected coexistent alpha thalassemia minor based on red blood cell indices. This case confirms the importance of the required confirmatory method to ensure a correct diagnosis since a misdiagnosis can lead to numerous adverse clinical or psychological effects for patients.

Vancomycin Induced Thrombocytopenia - Protracted Course in a Hemodialysis Patient.

Vancomycin induced thrombocytopenia (VIT) is an uncommon side effect of vancomycin which can manifest from mild petechiae to life-threatening bleed. Decreased renal clearance of vancomycin results in prolonged thrombocytopenia by antibody-mediated platelet destruction in the presence of vancomycin. Improvement in thrombocytopenia is achieved with the elimination of vancomycin. We describe a patient with end stage renal disease who experienced a protracted course of thrombocytopenia from vancomycin. We illustrate the mechanism of thrombocytopenia and the treatment modalities used by us and those described in literature. VIT is an important differential in patients with thrombocytopenia admitted to the hospital.

Effect of Stem Cell Transplant on Survival in Adult Patients With Acute Lymphoblastic Leukemia: NCDB Analysis.

BACKGROUND: A retrospective analysis was performed to investigate the survival outcomes in adult acute lymphoblastic leukemia (ALL) based on treatment received. MATERIALS AND METHODS: Data from 17,504 men and women (≥18 years of age) registered in the National Cancer Database who were diagnosed with ALL between 2004 and 2013 and had follow-up to the end of 2014, were analyzed. The primary predictor variable was treatment received, and overall survival was the outcome variable. Additional variables addressed and adjusted included gender, age, race, Charleston Comorbidity Index, level of education, income, insurance, distance traveled, facility type and diagnosing/treating facility. RESULTS: The mean age of patients was 48.8 years with a standard deviation of 19.3 years. In multivariate analysis, after adjusting for secondary predictor variables, treatment modality was a statistically significant predictor of overall survival from ALL. Relative to patients who were treated with chemotherapy only, the patients who got chemotherapy and stem cell transplant had a decreased risk of mortality by 39%. Of the 5,409 patients between the ages of 18 and 39 years i.e. adolescent and young adults (AYA), no statistically significant survival difference was found between patients treated with stem cell transplant and those not. CONCLUSION: Stem cell transplant led to improved survival for all age groups except the AYA.

Iatrogenic constipation from barium blockade: A case report.

Barolith, a mixture of inspissated barium and feces, is a rare complication of barium-contrast studies that lead to intestinal obstruction. With the high morbidity associated with barolith impaction, we recommend that physicians be more aware of complications, increase prompt diagnosis, and initiation of laxatives once discovered.

Plasmablastic Lymphoma, a Rare Entity in Bone Marrow with Unusual Immunophenotype and Challenging Differential Diagnosis.

Plasmablastic lymphoma (PBL) is an aggressive malignancy that usually occurs in the setting of immunosuppression. The immunohistochemical profile of PBL is that of terminally differentiated B lymphocytes. CD138, CD38, and MUM1 are usually immunopositive. However, pan B-cell markers such as CD20 and PAX-5 are usually negative. MYC rearrangement is the most commonly encountered genetic alteration, with immunoglobulin (IG), especially immunoglobulin heavy (IGH) chain, being the most frequent partner. We report a case of PBL in a 48-year-old human immunodeficiency virus- (HIV-) positive male who was admitted to the hospital with signs and symptoms suspicious for tumor lysis syndrome. Bone marrow examination revealed hypercellular marrow with trilineage hypoplasia and sheets of intermediate to large neoplastic cells with basophilic vacuolated cytoplasm comprising the majority of cellular elements of the bone marrow. The neoplastic cells were negative for conventional B-cell, T-cell, plasma cell, and myeloid markers, while flow cytometric analysis revealed an abnormal CD45-dim population that was partially weakly positive for CD71 and CD79b. The diagnosis was initially thought to be a high-grade primitive hematopoietic neoplasm, possibly an acute undifferentiated leukemia. BOB-1, however, was immunopositive in the neoplastic cells, confirming its B-cell origin. MYC was positive by immunohistochemistry and break-apart FISH, as were CD45, MUM-1, and EMA immunostains. There was immunoglobulin kappa (IGK) light chain gene rearrangement by polymerase chain reaction (PCR). Additionally, Epstein-Barr virus- (EBV-) encoded small RNAs (EBER) were positive by in situ hybridization (ISH). The tumor proliferation index by Ki-67 immunostaining approached 95%. Although the tumor cells were negative for CD38 and CD138, the diagnosis of PBL was still rendered. We recommend using a broad spectrum of B-cell markers, including BOB-1 and OCT-2, in such challenging cases of B-cell lymphomas with no expression of conventional B-cell markers. We also emphasize that the negative CD38 and CD138 should not exclude PBL from the differential diagnosis.

Dasatinib-Induced Rhabdomyolysis in a 33-Year-Old Patient with Chronic Myeloid Leukemia.

Rhabdomyolysis is a life-threatening syndrome due to breakdown of the skeletal muscle. It can be caused by massive trauma and crush injuries or occur as a side effect of medications. Here, we describe a case of a 33-year-old male with human immunodeficiency virus (HIV) and newly diagnosed chronic myeloid leukemia (CML) with severe life-threatening rhabdomyolysis due to a rare offending agent.

Use of Eltrombopag in Improving Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation.

Eltrombopag is a thrombopoietin agonist and has been used in aplastic anemia and post-transplantation thrombocytopenia. The c-MPL receptor is present on hematopoietic stem cells. There are no reports of eltrombopag utilization for improving poor graft function in the post-transplant setting. Here were report a case of a young female with post-transplant poor graft function as evident from the low absolute neutrophil count, anemia, and thrombocytopenia on day 60. Eltrombopag was started on day 72 and resulted in improvement in all 3 cell lines. The counts continued to be stable even after eltrombopag was discontinued. The patient tolerated the drug without significant side effects for 1 year.

Efficacy and safety of carfilzomib in relapsed and/or refractory multiple myeloma: systematic review and meta-analysis of 14 trials.

OBJECTIVE: Carfilzomib (Carf) is a second-generation proteasome inhibitor approved for patients with relapsed and/or refractory multiple myeloma (RRMM) who failed ≥ 1 prior lines of therapy. We performed a systematic review of Carf literature with meta-analysis to determine the efficacy and safety in RRMM patients. METHODS: Based on literature search, we included a total of 14 eligible phase I/II, phase II and phase III Carf based clinical trials. The cumulative incidence and odds ratios (OR) were calculated with random effect model, using ''R'' software with metaphor package. RESULTS: 2906 evaluable RRMM patients from published clinical trials included. The pooled overall response rate (ORR) was 45% (95% CI: 29-62). The pooled clinical benefit rate (CBR) was 56% (95% CI: 41-71). OR from 3 randomized clinical trials showed that Carf significantly improved ORR and CBR compared to control groups (OR 2.4, P < 0.0001; 2.02, P = 0.0007, respectively). Subgroup analysis showed significantly better ORR (P < 0.0001) and CBR (P < 0.001) with combination regimens compared to monotherapy. Response was significantly higher with high dose of Carf (>20/27 mg/m2) compared to standard dose (ORR 65% vs. 35%, P = 0.03). Compared to control group, the OR of developing cardiotoxicity (P = 0.002) and hypertension (P < 0.0001) were significantly higher with Carf, while no difference in peripheral neuropathy (P = 0.28). CONCLUSIONS: Carf produces significantly better responses with acceptable safety profile in RRMM patients. Combination regimens and higher dose Carf offers better response with no significant extra toxicity. Its efficacy is regardless of cytogenetics or disease stage. Incidences of cardiotoxicity and hypertension seem higher with Carf.

Automating Quality Oncology Practice Initiative Quality Measure NHL78a.

PURPOSE: Quality measurement and improvement is a focus of ASCO. In the era of electronic health records (EHRs), computerized order entry, and medication administration records, quality monitoring can be an automated process. The EHR data are usually stored within tables in a relational database management system. ASCO Quality Oncology Practice Initiative measure NHL78a (hepatitis B virus antigen test and hepatitis B core antibody test within 3 months before initiation of obinutuzumab, ofatumumab, or rituximab for patients with non-Hodgkin lymphoma) presents an opportunity for automation of a quality measure using existing data in the EHR. METHODS: We used a locally developed Structured Query Language (SQL) language procedure in the Microsoft SQL Query Manager to access the EPIC CLARITY database. Access to the relational database management system of the EHR permits rapid case identification (the denominator set) of the unique ID of all of the patients who have received one of the target medications (ie, obinutuzumab, ofatumumab, or rituximab). Then, we went through a six-step process to find the number of patients who passed or failed the quality measure. RESULTS: When the final SQL procedure executes, it takes < 5 seconds to see the result set for a 12-month period. The procedure can be changed to incorporate a desired date range. Once the SQL procedure is created, there is essentially no labor and low costs to run the procedure at specific time intervals. CONCLUSION: Our method of quality measurement using EHRs is cost effective, fast, and precise, and can be reproduced at other centers.

Effect of Radiation Therapy on Survival in Hodgkin's Lymphoma: A SEER Data Analysis.

BACKGROUND/AIM: Hodgkin's Lymphoma (HL) is curable in up to 80% of patients due, in part, to simultaneous advances in chemotherapy regimens as well as radiation therapy planning and delivery. Concerns regarding the historical use of large-field radiotherapy on overall survival have been published. In this study, we performed a Surveillance, epidemiology, and end results (SEER) data analysis to evaluate the impact of patients and treatments related factors on survival in HL. PATIENTS AND METHODS: Data from 39,700 adult patients registered in the SEER data with diagnosis of HL, between 1983-2011 and follow-up through 2012 were analyzed. Impact of patient demographics (sex, age, race, ethnicity, year of diagnosis, family income, education, unemployment, poverty level and stage of disease) and treatment characteristics (delivery of radiotherapy) on survival were evaluated via multivariate analysis. RESULTS: Median age was 36 years. Most patients were Ann Arbor Stage II (39%) at diagnosis with the remainder distributed evenly between the remaining stages (I, III, IV: 19-21%). In multivariate analysis, after adjusting for secondary predictor variables including stage of disease, Radiation therapy (RT) was a statistically significant predictor of overall survival from HL (HR=0.72, (95% CI=0.68-0.75). At follow up of more than 25 years, Kaplan-Meier analysis showed that RT improved survival for all patients, irrespective of stage. Factors associated with worse survival included older age, male sex, extra nodal disease, advanced stage, African-American race, and non-Hispanic ethnicity. CONCLUSION: Radiation therapy improved survival in patients with all stages of HL. Demographic and disease factors associated with worse survival in this study may be related to particular patterns of care and warrant additional study.