Maternal-fetal stressors during the gestational period, such as psychosocial stress, disease burden, and medication use, have been shown to significantly affect the neurological and biological development of the fetus. To our knowledge, no previous study in the literature has synthesized the role of these various stressors in neurodevelopment into a single concise review article. Maternal psychosocial stress has been shown to raise levels of stress hormones, such as corticotropin-releasing hormone and adrenocorticotropic hormone, which in turn signal the release of glucocorticoids (eg, cortisol) along with catecholamines in the mother and fetus. These cascades could potentially have significant effects on fetal neurodevelopment. Further, this article highlights that certain maternal infectious disease states, such as influenza and Toxoplasma gondii, are associated with increased risk of psychiatric disorders among offspring, including schizophrenia and neurocognitive delay. Investigators have also found that antibodies from autoimmune disease have direct neurotoxic effects on neural cell receptors, manifesting in future cognitive performance deficits. Additionally, we note that the effects of opioid analgesics on fetal neurodevelopment are not well elucidated but some existing literature has found increased rates of neural tube defects and delays in central nervous system development. In summary, there is a need for increased prenatal screening for a wide breadth of maternal stressors to mitigate negative effects on fetal neurodevelopment.
{"title":"Fetal Neurobehavioral Development: The Role of Maternal Psychosocial, Pathological, and Pharmacological Stress","authors":"T. Fenster, M. Rao, Yakov Mamzhi, Harry Tsou Jr","doi":"10.52504/001C.12642","DOIUrl":"https://doi.org/10.52504/001C.12642","url":null,"abstract":"Maternal-fetal stressors during the gestational period, such as psychosocial stress, disease burden, and medication use, have been shown to significantly affect the neurological and biological development of the fetus. To our knowledge, no previous study in the literature has synthesized the role of these various stressors in neurodevelopment into a single concise review article. Maternal psychosocial stress has been shown to raise levels of stress hormones, such as corticotropin-releasing hormone and adrenocorticotropic hormone, which in turn signal the release of glucocorticoids (eg, cortisol) along with catecholamines in the mother and fetus. These cascades could potentially have significant effects on fetal neurodevelopment. Further, this article highlights that certain maternal infectious disease states, such as influenza and Toxoplasma gondii, are associated with increased risk of psychiatric disorders among offspring, including schizophrenia and neurocognitive delay. Investigators have also found that antibodies from autoimmune disease have direct neurotoxic effects on neural cell receptors, manifesting in future cognitive performance deficits. Additionally, we note that the effects of opioid analgesics on fetal neurodevelopment are not well elucidated but some existing literature has found increased rates of neural tube defects and delays in central nervous system development. In summary, there is a need for increased prenatal screening for a wide breadth of maternal stressors to mitigate negative effects on fetal neurodevelopment.","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134518297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heart failure with preserved ejection fraction (HFpEF) is characterized by a left ventricular ejection fraction of 50% or greater. While heart failure with reduced ejection fraction (HFrEF) is well-characterized and has numerous treatment options, HFpEF remains poorly understood. HFpEF has long been termed *diastolic dysfunction*, because it was thought that fibrosis and impaired relaxation of the left ventricle could alone explain the underlying pathophysiology. However, recent research has identified additional mechanisms that influence HFpEF, specifically metabolic disorders and proinflammatory conditions. Despite this recent progress in elucidating the pathophysiology, there are still no approved treatment options that increase survival in patients with HFpEF. In the context of limited pharmacological options, stem cell therapy and cardiac biomarkers have emerged as potential breakthroughs in the treatment of HFpEF, but there has not yet been a review of their potential. This review evaluates the potential of cardiosphere-derived cells (CDCs), mesenchymal stromal cells (MSCs), and endothelial progenitor cells (EPCs) in the treatment of HFpEF. CDCs have shown promise, with a placebo-controlled animal trial demonstrating an increase in survival and a marked improvement in left ventricular end diastolic filling among the group treated with intracoronary infusion of CDCs. Additionally, with the newfound understanding of HFpEF pathophysiology, studies have also investigated the role MSCs and EPCs play in the inflammation associated with HFpEF, as well as the potential benefit these stem cells would bring to the treatment of HFpEF. While clinical trials are needed to confirm the safety and efficacy of these therapies, we offer insight into their potential, as well as a comprehensive summary of the pertinent clinical studies that are currently in progress. Embase, Ovid Medline, and PubMed were used to search all relevant literature for this review.
{"title":"Stem Cell Therapies and Treatment Advances for Heart Failure with Preserved Ejection Fraction","authors":"Monica Soni, B. Ferrell, C. Wikholm, L. Wilson","doi":"10.52504/001C.12344","DOIUrl":"https://doi.org/10.52504/001C.12344","url":null,"abstract":"Heart failure with preserved ejection fraction (HFpEF) is characterized by a left ventricular ejection fraction of 50% or greater. While heart failure with reduced ejection fraction (HFrEF) is well-characterized and has numerous treatment options, HFpEF remains poorly understood. HFpEF has long been termed *diastolic dysfunction*, because it was thought that fibrosis and impaired relaxation of the left ventricle could alone explain the underlying pathophysiology. However, recent research has identified additional mechanisms that influence HFpEF, specifically metabolic disorders and proinflammatory conditions. Despite this recent progress in elucidating the pathophysiology, there are still no approved treatment options that increase survival in patients with HFpEF. In the context of limited pharmacological options, stem cell therapy and cardiac biomarkers have emerged as potential breakthroughs in the treatment of HFpEF, but there has not yet been a review of their potential. This review evaluates the potential of cardiosphere-derived cells (CDCs), mesenchymal stromal cells (MSCs), and endothelial progenitor cells (EPCs) in the treatment of HFpEF. CDCs have shown promise, with a placebo-controlled animal trial demonstrating an increase in survival and a marked improvement in left ventricular end diastolic filling among the group treated with intracoronary infusion of CDCs. Additionally, with the newfound understanding of HFpEF pathophysiology, studies have also investigated the role MSCs and EPCs play in the inflammation associated with HFpEF, as well as the potential benefit these stem cells would bring to the treatment of HFpEF. While clinical trials are needed to confirm the safety and efficacy of these therapies, we offer insight into their potential, as well as a comprehensive summary of the pertinent clinical studies that are currently in progress. Embase, Ovid Medline, and PubMed were used to search all relevant literature for this review.","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"138 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2020-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134357541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Elizabeth Dente, Richard A. Farneth, Jennifer Purks, S. Torelli
Breast cancer research has traditionally focused on biological females who identify as women. Less is known about the incidence of breast cancer in transgender populations who identify with a gender that does not correspond with their birth sex. There are data to suggest a potential link between hormone replacement therapy (HRT) and breast cancer in transgender patients. While there is a need for more robust studies in this area, current data suggest there is no increased risk in female-to-male transgender men, and a potential increased risk in male-to-female transgender women. These studies also suggest that transgender patients face significant disparities in care. Clinicians require improved education to understand the potential risks associated with HRT, standards of cancer screening for transgender patients, and proper sensitivity in communication with this patient population. This review examines the existing literature, outlines the current data on the potential risks associated with HRT, and provides a 3-pronged approach to communicate risk, screen, and diagnose breast cancer in transgender patient populations. **Note: All authors contributed equally to this manuscript.**
{"title":"Evaluating Risks, Reported Cases and Screening Recommendations for Breast Cancer in Transgender Patients","authors":"Elizabeth Dente, Richard A. Farneth, Jennifer Purks, S. Torelli","doi":"10.52504/001c.7774","DOIUrl":"https://doi.org/10.52504/001c.7774","url":null,"abstract":"Breast cancer research has traditionally focused on biological females who identify as women. Less is known about the incidence of breast cancer in transgender populations who identify with a gender that does not correspond with their birth sex. There are data to suggest a potential link between hormone replacement therapy (HRT) and breast cancer in transgender patients. While there is a need for more robust studies in this area, current data suggest there is no increased risk in female-to-male transgender men, and a potential increased risk in male-to-female transgender women. These studies also suggest that transgender patients face significant disparities in care. Clinicians require improved education to understand the potential risks associated with HRT, standards of cancer screening for transgender patients, and proper sensitivity in communication with this patient population. This review examines the existing literature, outlines the current data on the potential risks associated with HRT, and provides a 3-pronged approach to communicate risk, screen, and diagnose breast cancer in transgender patient populations. \u0000\u0000**Note: All authors contributed equally to this manuscript.**","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"63 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126303380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jon D Turissini, Tammer Elmarsafi, K. Evans, P. Kim
A retrospective review was done for each wound (n = 223) in all patients (n = 191) who underwent Split Thickness Skin Graft (STSG) placement in the Wound Division at Georgetown University Hospital from January 2014 to March 2017 in order to determine the factors that significantly affect STSG take. In doing so, these factors that prove to significantly affect STSG take can be used to predict the possibility of graft failure, and, thus, determine if additional measures must be taken in order to improve the success of the skin graft. Patient medical records were examined for patient demographics, comorbidities, wound parameters, wound bed prep, post-operative dressing, 30 day graft outcomes, and 60 day graft outcomes. Statistical analysis was performed to determine the significance of each factor, and further analysis was done to determine the association and risk of the statistically significant factors. Statistical analysis showed a significant association between Negative Pressure Wound Therapy (NPWT) for wound bed dressing after STSG placement and successful STSG outcome compared to use of bolster only for the post-surgical wound (χ2 = 4.66, p=0.0308). The odds of STSG failure in patients who underwent NPWT were approximately 80% less than those who had bolster dressing used for their post-surgical dressing (OR = 0.203). These results indicate that NPWT after skin graft placement yields a greater success rate for split-thickness skin grafts than conventional bolster dressing. In terms of comorbidities, there was also a significant association between congestive heart failure (CHF) and STSG failure (χ2 = 4.12, p=0.0422). Patients with CHF were approximately 2.55 times more likely to have their STSG fail (OR = 2.55), indicating that CHF is a good predictor of split-thickness skin graft failure. It was also found that bacterial presence and STSG failure also showed an association (χ2 = 4.66, p=0.0308), in which patients with bacterial presence on the wound prior to debridement were approximately 2.89 times more likely to have STSG failure (OR = 2.89). Although bacterial presence prior to debridement showed an association with STSG failure, bacterial presence after debridement just prior to STSG placement did not show a significant correlation with STSG failure [nf = 52 (73.2%) versus ns = 95 (62.5%), (p = 0.1150)]. These results suggest that bacterial presence may also be a good predictor of graft failure, however it is possibly the strain of bacteria, not the presence of bacteria that predominantly affects skin graft take. In order to elucidate the role that bacteria plays in the success of STSG take, further experimental analysis is warranted.
{"title":"Major Risk Factors Contributing to Split Thickness Skin Graft Failure","authors":"Jon D Turissini, Tammer Elmarsafi, K. Evans, P. Kim","doi":"10.52504/001c.7755","DOIUrl":"https://doi.org/10.52504/001c.7755","url":null,"abstract":"A retrospective review was done for each wound (n = 223) in all patients (n = 191) who underwent Split Thickness Skin Graft (STSG) placement in the Wound Division at Georgetown University Hospital from January 2014 to March 2017 in order to determine the factors that significantly affect STSG take. In doing so, these factors that prove to significantly affect STSG take can be used to predict the possibility of graft failure, and, thus, determine if additional measures must be taken in order to improve the success of the skin graft. Patient medical records were examined for patient demographics, comorbidities, wound parameters, wound bed prep, post-operative dressing, 30 day graft outcomes, and 60 day graft outcomes. Statistical analysis was performed to determine the significance of each factor, and further analysis was done to determine the association and risk of the statistically significant factors. Statistical analysis showed a significant association between Negative Pressure Wound Therapy (NPWT) for wound bed dressing after STSG placement and successful STSG outcome compared to use of bolster only for the post-surgical wound (χ2 = 4.66, p=0.0308). The odds of STSG failure in patients who underwent NPWT were approximately 80% less than those who had bolster dressing used for their post-surgical dressing (OR = 0.203). These results indicate that NPWT after skin graft placement yields a greater success rate for split-thickness skin grafts than conventional bolster dressing. In terms of comorbidities, there was also a significant association between congestive heart failure (CHF) and STSG failure (χ2 = 4.12, p=0.0422). Patients with CHF were approximately 2.55 times more likely to have their STSG fail (OR = 2.55), indicating that CHF is a good predictor of split-thickness skin graft failure. It was also found that bacterial presence and STSG failure also showed an association (χ2 = 4.66, p=0.0308), in which patients with bacterial presence on the wound prior to debridement were approximately 2.89 times more likely to have STSG failure (OR = 2.89). Although bacterial presence prior to debridement showed an association with STSG failure, bacterial presence after debridement just prior to STSG placement did not show a significant correlation with STSG failure [nf = 52 (73.2%) versus ns = 95 (62.5%), (p = 0.1150)]. These results suggest that bacterial presence may also be a good predictor of graft failure, however it is possibly the strain of bacteria, not the presence of bacteria that predominantly affects skin graft take. In order to elucidate the role that bacteria plays in the success of STSG take, further experimental analysis is warranted.","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"59 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128719396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
**Introduction:** Primary pulmonary leiomyosarcomas are a group of rare malignant tumors. They are subdivided into those originating from pulmonary parenchyma, bronchial tree, or pulmonary arteries. They tend to expand locally, and presentation depends on the site of the tumor. Diagnosis can be challenging. **Case Presentation:** A 40-year-old woman presented with dyspnea and severe sepsis due to a lung mass and postobstructive pneumonia. She was diagnosed as having bilateral endobronchial primary pulmonary leiomyosarcoma and treated with bilobectomy; however, she died shortly after surgery due to complications. **Conclusion:** Considering the rarity of her condition, this case offers a unique opportunity to investigate its presentation, diagnosis, and treatment strategies through a study of the literature.
{"title":"Bilateral Primary Pulmonary Leiomyosarcoma: A Case Report","authors":"M. Magovern, S. Wachs, Virginia Malatack","doi":"10.52504/001c.7982","DOIUrl":"https://doi.org/10.52504/001c.7982","url":null,"abstract":"**Introduction:** Primary pulmonary leiomyosarcomas are a group of rare malignant tumors. They are subdivided into those originating from pulmonary parenchyma, bronchial tree, or pulmonary arteries. They tend to expand locally, and presentation depends on the site of the tumor. Diagnosis can be challenging. \u0000**Case Presentation:** A 40-year-old woman presented with dyspnea and severe sepsis due to a lung mass and postobstructive pneumonia. She was diagnosed as having bilateral endobronchial primary pulmonary leiomyosarcoma and treated with bilobectomy; however, she died shortly after surgery due to complications. \u0000**Conclusion:** Considering the rarity of her condition, this case offers a unique opportunity to investigate its presentation, diagnosis, and treatment strategies through a study of the literature.","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"13 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122275957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
We present a case of a nulliparous patient with a sudden diastasis of rectus abdominis (DRA) during labor. DRA is defined in literature as a separation of 2 muscle bellies of rectus abdominis of more than 2 fingerbreadths either 4.5 cm above or below the umbilicus.1 DRA is clinically recognized; however, there is limited knowledge on the prevalence, risk factors, and complications of DRA. Here, we present a patient who had an abrupt DRA during labor with herniation of bowel anterior to the fundus with associated abdominal pain. Due to similarity in presentation as uterine rupture, this case resulted in an elective cesarean delivery. Thus, this case report highlights the need to review DRA and uterine rupture and the associated risk factors to help health care professionals make prompt diagnoses and avoid elective primary cesarean delivery in an otherwise healthy, nulliparous patient.
{"title":"Sudden Diastasis of Rectus Abdominis During Labor: A Case Report","authors":"M. Sigdel, M. A. Fernández","doi":"10.52504/001c.7779","DOIUrl":"https://doi.org/10.52504/001c.7779","url":null,"abstract":"We present a case of a nulliparous patient with a sudden diastasis of rectus abdominis (DRA) during labor. DRA is defined in literature as a separation of 2 muscle bellies of rectus abdominis of more than 2 fingerbreadths either 4.5 cm above or below the umbilicus.1 DRA is clinically recognized; however, there is limited knowledge on the prevalence, risk factors, and complications of DRA. Here, we present a patient who had an abrupt DRA during labor with herniation of bowel anterior to the fundus with associated abdominal pain. Due to similarity in presentation as uterine rupture, this case resulted in an elective cesarean delivery. Thus, this case report highlights the need to review DRA and uterine rupture and the associated risk factors to help health care professionals make prompt diagnoses and avoid elective primary cesarean delivery in an otherwise healthy, nulliparous patient.","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125930921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Haque, M. Gratson, Jodi Woerle, Fitz Tavernier Jr
**Introduction:** Tens of thousands of patients die of major life-threatening bleeds every year while taking direct factor Xa inhibitors, a class of anticoagulant medications that until now had no reversal agent. In May 2018, the US Food and Drug Administration approved andexanet alfa (Andexxa), the first known reversal agent for a subset of direct factor Xa inhibitors. It has been reported to substantially reduce mortality rates for patients who experience a major bleed while taking rivaroxaban or apixaban. Andexxa is costly, however, ranging between US $24,750 and $49,500 for treatment. **Methods:** To explore the cost-effectiveness of Andexxa, a Markov model was generated using existing Andexxa trial data and related literature. Multiple 1-way and 2-way sensitivity analyses were also constructed to delineate the impact Andexxa would need to have on mortality rates and health-related quality of life to meet the willingness-to-pay thresholds ranging between $50,000 and $150,000. The model included a hypothetical cohort of patients aged 65 years at an increased risk of stroke due to nonvalvular atrial fibrillation and with no contraindication to anticoagulation. **Results:** The Markov model showed that the incremental cost-effectiveness ratio of Andexxa over the standard of care is $211,056 for an intracranial hemorrhage and $40,718 for a gastrointestinal bleed. Sensitivity analyses further indicated that while Andexxa may be cost-effective to treat gastrointestinal bleeds, medication trial data will likely need to show significant impact on a patient’s quality of life and relative risk of death following an intracranial bleed to be cost-effective. **Discussion:** Although the application of these findings is restricted due to limited trial data, beginning to understand the cost-effectiveness of Andexxa provides policymakers important insight into the economic value of the intervention.
{"title":"Beginning to Understand the Cost-effectiveness of Andexxa","authors":"M. Haque, M. Gratson, Jodi Woerle, Fitz Tavernier Jr","doi":"10.52504/001c.7777","DOIUrl":"https://doi.org/10.52504/001c.7777","url":null,"abstract":"**Introduction:** Tens of thousands of patients die of major life-threatening bleeds every year while taking direct factor Xa inhibitors, a class of anticoagulant medications that until now had no reversal agent. In May 2018, the US Food and Drug Administration approved andexanet alfa (Andexxa), the first known reversal agent for a subset of direct factor Xa inhibitors. It has been reported to substantially reduce mortality rates for patients who experience a major bleed while taking rivaroxaban or apixaban. Andexxa is costly, however, ranging between US $24,750 and $49,500 for treatment. \u0000**Methods:** To explore the cost-effectiveness of Andexxa, a Markov model was generated using existing Andexxa trial data and related literature. Multiple 1-way and 2-way sensitivity analyses were also constructed to delineate the impact Andexxa would need to have on mortality rates and health-related quality of life to meet the willingness-to-pay thresholds ranging between $50,000 and $150,000. The model included a hypothetical cohort of patients aged 65 years at an increased risk of stroke due to nonvalvular atrial fibrillation and with no contraindication to anticoagulation. \u0000**Results:** The Markov model showed that the incremental cost-effectiveness ratio of Andexxa over the standard of care is $211,056 for an intracranial hemorrhage and $40,718 for a gastrointestinal bleed. Sensitivity analyses further indicated that while Andexxa may be cost-effective to treat gastrointestinal bleeds, medication trial data will likely need to show significant impact on a patient’s quality of life and relative risk of death following an intracranial bleed to be cost-effective. \u0000**Discussion:** Although the application of these findings is restricted due to limited trial data, beginning to understand the cost-effectiveness of Andexxa provides policymakers important insight into the economic value of the intervention.","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"48 10","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"114130437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
While the prognosis for glioblastoma multiforme remains grim with a median survival of 12-15 months, PVS(RIPO), a recombinant oncolytic poliovirus, is emerging as a novel immunotherapeutic approach to treat malignancy. PVS(RIPO) is a genetically recombinant poliovirus-rhinovirus chimera that demonstrates antitumor efficacy via two main mechanisms: cytotoxicity and its subsequent immunogenenic response. Here, I review the rationale for oncolytic viruses in the treatment of glioblastoma, the development of PVS(RIPO), the underlying mechanisms of action of PVS(RIPO), the critical preclinical trial that demonstrated its safety and efficacy, the ongoing clinical trials that have shown promising preliminary data, and limitations of PVS(RIPO) as an oncolytic virus for glioblastoma therapy.
{"title":"Recombinant Oncolytic Poliovirus for Glioblastoma: A Current Review of PVS(RIPO)","authors":"A. B. Carpenter","doi":"10.52504/001c.7789","DOIUrl":"https://doi.org/10.52504/001c.7789","url":null,"abstract":"While the prognosis for glioblastoma multiforme remains grim with a median survival of 12-15 months, PVS(RIPO), a recombinant oncolytic poliovirus, is emerging as a novel immunotherapeutic approach to treat malignancy. PVS(RIPO) is a genetically recombinant poliovirus-rhinovirus chimera that demonstrates antitumor efficacy via two main mechanisms: cytotoxicity and its subsequent immunogenenic response. Here, I review the rationale for oncolytic viruses in the treatment of glioblastoma, the development of PVS(RIPO), the underlying mechanisms of action of PVS(RIPO), the critical preclinical trial that demonstrated its safety and efficacy, the ongoing clinical trials that have shown promising preliminary data, and limitations of PVS(RIPO) as an oncolytic virus for glioblastoma therapy.","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128916630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Case Presentation : An 89-year-old woman with a history of atrial fibrillation, coronary artery disease, hypertension, and recent hospitalization for intraparenchymal and intraventricular hemorrhage presented with new-onset critical thrombocytopenia secondary to amiodarone, which had started approximately 1.5 months prior to presentation. Discussion : The patient’s treatment with amiodarone was stopped on the first day of admission, at which time her platelet count was . She received transfusions of 4 units of platelets during her hospital stay, and her platelet count was at discharge. It increased to at follow-up with outpatient hematology 15 days after presentation and was within normal limits 7 months after hospitalization. There are 2 published reports detailing 5 separate cases of amiodarone-induced immune thrombocytopenia, and at least 8 reports of amiodarone-induced bone marrow granulomas resulting in pancytopenia. Because the patient did not have pancytopenia consistent with myelosuppression, her presentation was not reflective of bone marrow granulomas or a direct, nonimmune-mediated insult. However, the return of her platelet count to a normal level was delayed compared with the timeline presented in previous cases of both amiodarone and non-amiodarone immune-mediated thrombocytopenias. This delay in return to normal platelet count was likely secondary to the patient’s older age in the context of amiodarone’s lipophilic nature and very long half-life. Conclusion : Although a rare complication of amiodarone use, thrombocytopenia should be considered by physicians who prescribe this drug. should prompt a complete blood count, discontinuation of the drug, and monitoring for resolution. If the platelet count recovers and amiodarone is found to be responsible, the medication should not be restarted, and amiodarone should be considered a drug allergy. thrombocytopenia when beginning therapy and to surveil patients with complete blood count monitoring. This patient experienced a late-onset thrombocytopenia after beginning amiodarone, followed by a delayed recovery to normal platelet counts. As previous literature has reported, platelet recovery after amiodarone-induced thrombocytopenia is longer than observed with other drugs. Although this timeline of late onset and delayed recovery is more consistent with previous reports of amiodarone-mediated direct nonimmune toxicity or bone marrow granulomas, the patient’s normal white blood cell count and only mild anemia argue against a nonimmune cause of thrombocytopenia. Her antibody test results were negative, but previous studies have shown immune-mediated amiodarone-Amiodarone-Induced
{"title":"Amiodarone-Induced Thrombocytopenia: A Case Report","authors":"J. Burlile, Amit Pathak","doi":"10.52504/001c.7797","DOIUrl":"https://doi.org/10.52504/001c.7797","url":null,"abstract":"Case Presentation : An 89-year-old woman with a history of atrial fibrillation, coronary artery disease, hypertension, and recent hospitalization for intraparenchymal and intraventricular hemorrhage presented with new-onset critical thrombocytopenia secondary to amiodarone, which had started approximately 1.5 months prior to presentation. Discussion : The patient’s treatment with amiodarone was stopped on the first day of admission, at which time her platelet count was . She received transfusions of 4 units of platelets during her hospital stay, and her platelet count was at discharge. It increased to at follow-up with outpatient hematology 15 days after presentation and was within normal limits 7 months after hospitalization. There are 2 published reports detailing 5 separate cases of amiodarone-induced immune thrombocytopenia, and at least 8 reports of amiodarone-induced bone marrow granulomas resulting in pancytopenia. Because the patient did not have pancytopenia consistent with myelosuppression, her presentation was not reflective of bone marrow granulomas or a direct, nonimmune-mediated insult. However, the return of her platelet count to a normal level was delayed compared with the timeline presented in previous cases of both amiodarone and non-amiodarone immune-mediated thrombocytopenias. This delay in return to normal platelet count was likely secondary to the patient’s older age in the context of amiodarone’s lipophilic nature and very long half-life. Conclusion : Although a rare complication of amiodarone use, thrombocytopenia should be considered by physicians who prescribe this drug. should prompt a complete blood count, discontinuation of the drug, and monitoring for resolution. If the platelet count recovers and amiodarone is found to be responsible, the medication should not be restarted, and amiodarone should be considered a drug allergy. thrombocytopenia when beginning therapy and to surveil patients with complete blood count monitoring. This patient experienced a late-onset thrombocytopenia after beginning amiodarone, followed by a delayed recovery to normal platelet counts. As previous literature has reported, platelet recovery after amiodarone-induced thrombocytopenia is longer than observed with other drugs. Although this timeline of late onset and delayed recovery is more consistent with previous reports of amiodarone-mediated direct nonimmune toxicity or bone marrow granulomas, the patient’s normal white blood cell count and only mild anemia argue against a nonimmune cause of thrombocytopenia. Her antibody test results were negative, but previous studies have shown immune-mediated amiodarone-Amiodarone-Induced","PeriodicalId":340325,"journal":{"name":"Georgetown Medical Review","volume":"81 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2019-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122465170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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