Objectives:The coronavirus disease 2019 pandemic caused substantial changes to healthcare deliver... more Objectives:The coronavirus disease 2019 pandemic caused substantial changes to healthcare delivery and antibiotic prescribing beginning in March 2020. To assess pandemic impact on Clostridioides difficile infection (CDI) rates, we described patients and trends in facility-level incidence, testing rates, and percent positivity during 2019–2020 in a large cohort of US hospitals.Methods:We estimated and compared rates of community-onset CDI (CO-CDI) per 10,000 discharges, hospital-onset CDI (HO-CDI) per 10,000 patient days, and C. difficile testing rates per 10,000 discharges in 2019 and 2020. We calculated percent positivity as the number of inpatients diagnosed with CDI over the total number of discharges with a test for C. difficile. We used an interrupted time series (ITS) design with negative binomial and logistic regression models to describe level and trend changes in rates and percent positivity before and after March 2020.Results:In pairwise comparisons, overall CO-CDI rates d...
e18738 Background: Classical Hodgkin lymphoma (cHL) is a B-cell neoplasm which affects approximat... more e18738 Background: Classical Hodgkin lymphoma (cHL) is a B-cell neoplasm which affects approximately 8,500 new patients annually. The initial remission rate is greater than 80%; however, 10-30% will have refractory or relapsed disease (R/R). Both Brentuximab vedotin (BV) and nivolumab (Nivo) have recently been approved for the treatment of R/R cHL. Previous studies have shown BV+Nivo to be well tolerated, with high response rates and progression free survival (PFS) in two prospective studies. However, no real-world data is available yet for this combination. Here we present clinical characteristics and outcomes of a single institution cohort of patients with cHL who received BV+Nivo. Methods: A retrospective chart review was completed of all patients with cHL who were treated with BV+Nivo at Moffitt Cancer Center between 2018 and 2021. Baseline characteristics and treatment details were obtained. PFS and overall survival (OS) were evaluated using the Kaplan-Meier curve. Results: A t...
Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cell... more Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% of MDS patients fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due to lack of approved second-line treatment options. As cancer stem cells are the seeds of disease progression, we investigated the biological properties of the MDS HSCs that drive disease evolution, seeking to uncover vulnerabilities that could be therapeutically exploited. Through integrative molecular profiling of HSCs and progenitor cells in large patient cohorts, we found that MDS HSCs in two distinct differentiation states are maintained throughout the clinical course of the disease, and expand at progression, depending on recurrent activation of the anti-apoptotic regulator BCL-2 or nuclear factor-kappa B-mediated survival pathways. Pharmacologically inhibi...
Introduction: The management of classical Hodgkin lymphoma (cHL) with first line therapy continue... more Introduction: The management of classical Hodgkin lymphoma (cHL) with first line therapy continues to evolve resulting in some of the best outcomes in oncology. Around 20-30% of patients with cHL relapse and have to undergo salvage chemotherapy followed by autologous hematopoietic cell transplant (Auto HCT). There are no randomized trials comparing the most common regimens used in second line to date. With the introduction of newer agents in the treatment of cHL, it is essential to identify patients that might benefit from a different approach in first salvage setting. The aim of this study is to assess patterns of relapse and differences in outcomes based on salvage regimens. Methods: We retrospectively identified 193 consecutive patients with cHL treated in our academic medical center. Adult patients treated with ABVD (Adriamycin, Bleomycin, Vinblastine, Decarbazine) for first line were included. The three most common salvage regimens used in our institution included ICE (Ifosfami...
The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions o... more The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells’ self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA...
Introduction: The standard of care for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL)... more Introduction: The standard of care for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is salvage therapy followed by autologous hematopoietic stem cell transplant (auto-HCT). Pre-apheresis absolute lymphocyte count (PA-ALC) is an independent prognostic factor for overall survival (OS) after transplant. We aimed to evaluate the effect of absolute lymphocyte count following auto-HCT and hypothesized that a higher post-transplant ALC at day +15 (PT-ALC) correlates with improved OS. Methods: A retrospective review was performed on patients with R/R cHL who underwent auto-HCT at Moffitt Cancer Center from 2000-2020. The following patient characteristics were collected: age at diagnosis, gender, initial stage and presence of B symptoms. Pretransplant variables including chemotherapy, number of cycles, response to therapy, and time from last chemo to apheresis were collected. Receiver-operator characteristics (ROC) curve was used to identify the ideal PT-ALC to predict overall ...
Introduction: T-cell prolymphocytic leukemia (T-PLL) is a rare type of mature T-cell neoplasm wit... more Introduction: T-cell prolymphocytic leukemia (T-PLL) is a rare type of mature T-cell neoplasm with a poor prognosis. Up to 30% of patients initially present with indolent disease course that may be observed until progression to T-PLL with aggressive behavior. We aimed to compare the clinicopathologic characteristics and outcomes of patients with initially indolent versus aggressive disease. We hypothesized that patients with indolent disease have less cytogenetic abnormalities and a favorable overall survival (OS). Methods: We identified 65 patients diagnosed with T-PLL between 2004 and 2020 who were treated at Moffitt Cancer Center. Clinical presentation, laboratory parameters, and bone marrow biopsy at the time of diagnosis were retrospectively reviewed. Patients were categorized into two groups: indolent or aggressive disease type. Patients were considered indolent if they did not have symptoms requiring immediate treatment such as B symptoms or fatigue, symptomatic lymphadenopat...
Background: Epidemiological studies have utilized administrative discharge diagnosis codes to ide... more Background: Epidemiological studies have utilized administrative discharge diagnosis codes to identify methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA) infections and trends, despite debate regarding the accuracy of utilizing codes for this purpose. We assessed the sensitivity and positive predictive value (PPV) of MRSA- and MSSA-specific diagnosis codes, trends, characteristics, and outcomes of S. aureus hospitalizations by method of identification. Methods: Clinical micro biology results and discharge data from geographically diverse US hospitals participating in the Premier Healthcare Database from 2012–2017 were used to identify monthly rates of MRSA and MSSA. Positive MRSA or MSSA clinical cultures and/or a MRSA- or MSSA-specific International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9/10 CM) diagnosis codes from adult inpatients (aged ≥18 years) were included as S. aureus hospitalizations. Septicemia was ...
Classical Hodgkin lymphoma is curable; however, relapsed/refractory disease results in high morbi... more Classical Hodgkin lymphoma is curable; however, relapsed/refractory disease results in high morbidity and mortality. This is a single-institution, retrospective study of 727 patients with classical Hodgkin lymphoma. Clinicopathologic features, prognostic factors, and treatment outcomes are defined. Outcomes are comparable to those reported in previous studies, with poor prognostic factors being older age, advanced stage, presence of B symptoms, and higher International Prognostic Score. Introduction: Classical Hodgkin lymphoma (cHL) is a curable malignancy, with a complete remission rate of approximately 90%. However, relapse remains a significant cause of mortality. Prognostic factors are useful in guiding therapy. This is a large, single-institution study defining the clinicopathologic features, prognostic factors, and treatment outcomes of patients with cHL. Patients and Methods: We reviewed 727 patients with cHL treated at H. Lee Moffitt Cancer Center and Research Institute from 1990 to 2017. Data on demographics, laboratory studies, and disease statuses were collected from the institutional database and electronic medical records. Statistical analyses, overall survival (OS), progression-free survival (PFS), and multivariate analyses were performed. Results: The median age was 35 years. Fifty-four percent of patients were men; 45.6% had advanced stage disease; 82% were treated with ABVD (doxorubicin hydrochloride [adriamycin], bleomycin sulfate, vincristine, and dacarbazine) as frontline therapy; and 70% achieved complete response. The median PFS after first-line treatment was 16.8 years. The median OS of patients with early stage and advanced stage cHL was 19 and 12.9 years, respectively. Poor prognostic factors for OS included older age, advanced stage disease, presence of B symptoms, and a higher International Prognostic Score. Conclusion: Despite high cure rates, cHL accounted for the cause of death in 47% of patients who died during followup. Prognostic factors, such as age, stage at diagnosis, International Prognostic Score, and B symptoms, are helpful to guide treatment. Outcomes observed in this study are comparable with those reported in previously published studies.
ABSTRACT Students pursuing careers in health professions may initially approach their training wi... more ABSTRACT Students pursuing careers in health professions may initially approach their training with preconceived ideas and perceptions of those who practice different health-related careers. Little research has been conducted on athletic training students and professional stereotypes or athletic training students and interprofessional education in general. Because interprofessional education may provide some positive effects on stereotypes, the goal of this study was to measure undergraduate health professions student stereotypes of athletic training students before and after an interprofessional case study program. Undergraduate nursing and public health interprofessional case study program participants assessed various relational and intrapersonal capabilities for their own professions and the athletic training profession, pre-post-program. For nursing student participants with athletic training students on their team, perceptions of their own profession and the athletic training profession significantly (p <.05) increased as compared to those with no athletic training student on their team. For public health student participants, although scores increased, no significant differences were found. Interprofessional collaborative experiences may decrease negative stereotypes of other professions, including athletic training.
Mediterranean Journal of Hematology and Infectious Diseases, 2018
We report five patients with human immunodeficiency virus-1/acquired immunodeficiency syndrome (H... more We report five patients with human immunodeficiency virus-1/acquired immunodeficiency syndrome (HIV-1/AIDS) who developed T-cell large granular lymphocytic leukemia (T-LGLL). None of the patients fulfilled criteria for diagnosis of diffuse infiltrative lymphocyte syndrome (DILS) or HIV-associated CD8+ lymphocytosis syndrome at the time of diagnosis of LGLL. The immunophenotype of malignant T-cells was identical in three patients with co-expression of CD3, CD8, CD57, and T-cell receptor (TCR) alpha/beta. Three out of five patients were also diagnosed with clonal disorders of B-cell origin including diffuse large B-cell lymphoma, Burkitt’s lymphoma, and monoclonal gammopathy of undetermined significance (MGUS). Two patients developed cytopenias due to T-LGLL prompting initiation of therapy. Our study suggests that chronic viral infection with HIV can contribute to evolution of T-LGLL. Clinical and laboratory characteristics of T-LGLL associated with HIV-1/AIDS resemble those of immun...
Objectives:The coronavirus disease 2019 pandemic caused substantial changes to healthcare deliver... more Objectives:The coronavirus disease 2019 pandemic caused substantial changes to healthcare delivery and antibiotic prescribing beginning in March 2020. To assess pandemic impact on Clostridioides difficile infection (CDI) rates, we described patients and trends in facility-level incidence, testing rates, and percent positivity during 2019–2020 in a large cohort of US hospitals.Methods:We estimated and compared rates of community-onset CDI (CO-CDI) per 10,000 discharges, hospital-onset CDI (HO-CDI) per 10,000 patient days, and C. difficile testing rates per 10,000 discharges in 2019 and 2020. We calculated percent positivity as the number of inpatients diagnosed with CDI over the total number of discharges with a test for C. difficile. We used an interrupted time series (ITS) design with negative binomial and logistic regression models to describe level and trend changes in rates and percent positivity before and after March 2020.Results:In pairwise comparisons, overall CO-CDI rates d...
e18738 Background: Classical Hodgkin lymphoma (cHL) is a B-cell neoplasm which affects approximat... more e18738 Background: Classical Hodgkin lymphoma (cHL) is a B-cell neoplasm which affects approximately 8,500 new patients annually. The initial remission rate is greater than 80%; however, 10-30% will have refractory or relapsed disease (R/R). Both Brentuximab vedotin (BV) and nivolumab (Nivo) have recently been approved for the treatment of R/R cHL. Previous studies have shown BV+Nivo to be well tolerated, with high response rates and progression free survival (PFS) in two prospective studies. However, no real-world data is available yet for this combination. Here we present clinical characteristics and outcomes of a single institution cohort of patients with cHL who received BV+Nivo. Methods: A retrospective chart review was completed of all patients with cHL who were treated with BV+Nivo at Moffitt Cancer Center between 2018 and 2021. Baseline characteristics and treatment details were obtained. PFS and overall survival (OS) were evaluated using the Kaplan-Meier curve. Results: A t...
Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cell... more Myelodysplastic syndromes (MDS) are heterogeneous neoplastic disorders of hematopoietic stem cells (HSCs). The current standard of care for patients with MDS is hypomethylating agent (HMA)-based therapy; however, almost 50% of MDS patients fail HMA therapy and progress to acute myeloid leukemia, facing a dismal prognosis due to lack of approved second-line treatment options. As cancer stem cells are the seeds of disease progression, we investigated the biological properties of the MDS HSCs that drive disease evolution, seeking to uncover vulnerabilities that could be therapeutically exploited. Through integrative molecular profiling of HSCs and progenitor cells in large patient cohorts, we found that MDS HSCs in two distinct differentiation states are maintained throughout the clinical course of the disease, and expand at progression, depending on recurrent activation of the anti-apoptotic regulator BCL-2 or nuclear factor-kappa B-mediated survival pathways. Pharmacologically inhibi...
Introduction: The management of classical Hodgkin lymphoma (cHL) with first line therapy continue... more Introduction: The management of classical Hodgkin lymphoma (cHL) with first line therapy continues to evolve resulting in some of the best outcomes in oncology. Around 20-30% of patients with cHL relapse and have to undergo salvage chemotherapy followed by autologous hematopoietic cell transplant (Auto HCT). There are no randomized trials comparing the most common regimens used in second line to date. With the introduction of newer agents in the treatment of cHL, it is essential to identify patients that might benefit from a different approach in first salvage setting. The aim of this study is to assess patterns of relapse and differences in outcomes based on salvage regimens. Methods: We retrospectively identified 193 consecutive patients with cHL treated in our academic medical center. Adult patients treated with ABVD (Adriamycin, Bleomycin, Vinblastine, Decarbazine) for first line were included. The three most common salvage regimens used in our institution included ICE (Ifosfami...
The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions o... more The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells’ self-renewal capabilities and eventually leads to their exhaustion. Mechanistically, we demonstrate that targeting members of the Ifi20x/IFI16 family of cytosolic DNA sensors using the oligodeoxynucleotide A151, which comprises four repeats of the TTAGGG motif of the telomeric DNA...
Introduction: The standard of care for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL)... more Introduction: The standard of care for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) is salvage therapy followed by autologous hematopoietic stem cell transplant (auto-HCT). Pre-apheresis absolute lymphocyte count (PA-ALC) is an independent prognostic factor for overall survival (OS) after transplant. We aimed to evaluate the effect of absolute lymphocyte count following auto-HCT and hypothesized that a higher post-transplant ALC at day +15 (PT-ALC) correlates with improved OS. Methods: A retrospective review was performed on patients with R/R cHL who underwent auto-HCT at Moffitt Cancer Center from 2000-2020. The following patient characteristics were collected: age at diagnosis, gender, initial stage and presence of B symptoms. Pretransplant variables including chemotherapy, number of cycles, response to therapy, and time from last chemo to apheresis were collected. Receiver-operator characteristics (ROC) curve was used to identify the ideal PT-ALC to predict overall ...
Introduction: T-cell prolymphocytic leukemia (T-PLL) is a rare type of mature T-cell neoplasm wit... more Introduction: T-cell prolymphocytic leukemia (T-PLL) is a rare type of mature T-cell neoplasm with a poor prognosis. Up to 30% of patients initially present with indolent disease course that may be observed until progression to T-PLL with aggressive behavior. We aimed to compare the clinicopathologic characteristics and outcomes of patients with initially indolent versus aggressive disease. We hypothesized that patients with indolent disease have less cytogenetic abnormalities and a favorable overall survival (OS). Methods: We identified 65 patients diagnosed with T-PLL between 2004 and 2020 who were treated at Moffitt Cancer Center. Clinical presentation, laboratory parameters, and bone marrow biopsy at the time of diagnosis were retrospectively reviewed. Patients were categorized into two groups: indolent or aggressive disease type. Patients were considered indolent if they did not have symptoms requiring immediate treatment such as B symptoms or fatigue, symptomatic lymphadenopat...
Background: Epidemiological studies have utilized administrative discharge diagnosis codes to ide... more Background: Epidemiological studies have utilized administrative discharge diagnosis codes to identify methicillin-resistant and methicillin-sensitive Staphylococcus aureus (MRSA and MSSA) infections and trends, despite debate regarding the accuracy of utilizing codes for this purpose. We assessed the sensitivity and positive predictive value (PPV) of MRSA- and MSSA-specific diagnosis codes, trends, characteristics, and outcomes of S. aureus hospitalizations by method of identification. Methods: Clinical micro biology results and discharge data from geographically diverse US hospitals participating in the Premier Healthcare Database from 2012–2017 were used to identify monthly rates of MRSA and MSSA. Positive MRSA or MSSA clinical cultures and/or a MRSA- or MSSA-specific International Classification of Diseases, Ninth/Tenth Revision, Clinical Modification (ICD-9/10 CM) diagnosis codes from adult inpatients (aged ≥18 years) were included as S. aureus hospitalizations. Septicemia was ...
Classical Hodgkin lymphoma is curable; however, relapsed/refractory disease results in high morbi... more Classical Hodgkin lymphoma is curable; however, relapsed/refractory disease results in high morbidity and mortality. This is a single-institution, retrospective study of 727 patients with classical Hodgkin lymphoma. Clinicopathologic features, prognostic factors, and treatment outcomes are defined. Outcomes are comparable to those reported in previous studies, with poor prognostic factors being older age, advanced stage, presence of B symptoms, and higher International Prognostic Score. Introduction: Classical Hodgkin lymphoma (cHL) is a curable malignancy, with a complete remission rate of approximately 90%. However, relapse remains a significant cause of mortality. Prognostic factors are useful in guiding therapy. This is a large, single-institution study defining the clinicopathologic features, prognostic factors, and treatment outcomes of patients with cHL. Patients and Methods: We reviewed 727 patients with cHL treated at H. Lee Moffitt Cancer Center and Research Institute from 1990 to 2017. Data on demographics, laboratory studies, and disease statuses were collected from the institutional database and electronic medical records. Statistical analyses, overall survival (OS), progression-free survival (PFS), and multivariate analyses were performed. Results: The median age was 35 years. Fifty-four percent of patients were men; 45.6% had advanced stage disease; 82% were treated with ABVD (doxorubicin hydrochloride [adriamycin], bleomycin sulfate, vincristine, and dacarbazine) as frontline therapy; and 70% achieved complete response. The median PFS after first-line treatment was 16.8 years. The median OS of patients with early stage and advanced stage cHL was 19 and 12.9 years, respectively. Poor prognostic factors for OS included older age, advanced stage disease, presence of B symptoms, and a higher International Prognostic Score. Conclusion: Despite high cure rates, cHL accounted for the cause of death in 47% of patients who died during followup. Prognostic factors, such as age, stage at diagnosis, International Prognostic Score, and B symptoms, are helpful to guide treatment. Outcomes observed in this study are comparable with those reported in previously published studies.
ABSTRACT Students pursuing careers in health professions may initially approach their training wi... more ABSTRACT Students pursuing careers in health professions may initially approach their training with preconceived ideas and perceptions of those who practice different health-related careers. Little research has been conducted on athletic training students and professional stereotypes or athletic training students and interprofessional education in general. Because interprofessional education may provide some positive effects on stereotypes, the goal of this study was to measure undergraduate health professions student stereotypes of athletic training students before and after an interprofessional case study program. Undergraduate nursing and public health interprofessional case study program participants assessed various relational and intrapersonal capabilities for their own professions and the athletic training profession, pre-post-program. For nursing student participants with athletic training students on their team, perceptions of their own profession and the athletic training profession significantly (p <.05) increased as compared to those with no athletic training student on their team. For public health student participants, although scores increased, no significant differences were found. Interprofessional collaborative experiences may decrease negative stereotypes of other professions, including athletic training.
Mediterranean Journal of Hematology and Infectious Diseases, 2018
We report five patients with human immunodeficiency virus-1/acquired immunodeficiency syndrome (H... more We report five patients with human immunodeficiency virus-1/acquired immunodeficiency syndrome (HIV-1/AIDS) who developed T-cell large granular lymphocytic leukemia (T-LGLL). None of the patients fulfilled criteria for diagnosis of diffuse infiltrative lymphocyte syndrome (DILS) or HIV-associated CD8+ lymphocytosis syndrome at the time of diagnosis of LGLL. The immunophenotype of malignant T-cells was identical in three patients with co-expression of CD3, CD8, CD57, and T-cell receptor (TCR) alpha/beta. Three out of five patients were also diagnosed with clonal disorders of B-cell origin including diffuse large B-cell lymphoma, Burkitt’s lymphoma, and monoclonal gammopathy of undetermined significance (MGUS). Two patients developed cytopenias due to T-LGLL prompting initiation of therapy. Our study suggests that chronic viral infection with HIV can contribute to evolution of T-LGLL. Clinical and laboratory characteristics of T-LGLL associated with HIV-1/AIDS resemble those of immun...
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