Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor protei... more Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding intermediaries, which are deposited in target tissues causing progressive organ damage. In all forms of amyloidosis, vital organs may fail; depending on the specific amyloidosis type, this may occur rapidly or progress slowly. Beyond therapies to reduce the precursor protein (chemotherapy for light chain [AL] amyloidosis, anti-inflammatory therapy in serum A amyloidosis [AA], and antisense RNA therapy in transthyretin amyloidosis [ATTR]), organ transplantation may also be a means to reduce amyloidogenic protein, e.g., in types of amyloidosis in which the variant precursor is produced by the liver. Heart transplantation is a life-saving approach to the treatment of patients with advanced cardiac amyloidosis; however, amyloidosis may still be considered a contraindication to the procedure despite data supporting improved outcomes,...
1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated ... more 1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.5 years) before the administration of anti-myeloma treatment and at best response to bortezomib-based therapy. suPAR was measured in the serum of all patients and of 24 healthy matched controls, using an immuno-enzymatic assay (ViroGates, Denmark). (3) Results: suPAR levels were elevated in NDMM patients at diagnosis compared to healthy individuals (p < 0.001). suPAR levels strongly correlated with disease stage (p-ANOVA < 0.001). suPAR levels both at diagnosis and at best response negatively correlated with estimated glomerular filtration rate (eGFR) values (p < 0.001). Interestingly, no significance changes in suPAR levels were observed at best response compared to baseline values (p = 0.31) among 18 responding patients with baseline eGFR < 50 mL/min/1.73 m 2 . (4) Conclusions: SuPAR levels reflect renal function in NDMM patients treated with bortezomib-based induction. Responders may have elevated circulating suPAR levels, possibly reflecting persistent kidney damage, despite their renal response.
Although COVID-19 presents primarily as a lower respiratory tract infection transmitted via air d... more Although COVID-19 presents primarily as a lower respiratory tract infection transmitted via air droplets, increasing data suggest multiorgan involvement in patients that are infected. This systemic involvement is postulated to be mainly related to the SARS-CoV-2 virus binding on angiotensin-converting enzyme 2 (ACE2) receptors located on several different human cells. Lung involvement is the most common serious manifestation of the disease, ranging from asymptomatic disease or mild pneumonia, to severe disease associated with hypoxia, critical disease associated with shock, respiratory failure and multiorgan failure or death. Among patients with COVID-19, underlying cardiovascular comorbidities including hypertension, diabetes and especially cardiovascular disease, has been associated with adverse outcomes, whereas the emergence of cardiovascular complications, including myocardial injury, heart failure and arrhythmias, has been associated with poor survival. Gastrointestinal symptoms are also frequently encountered and may persist for several days. Haematological complications are frequent as well and have been associated with poor prognosis. Furthermore, recent studies have reported that over a third of infected patients develop a broad spectrum of neurological symptoms affecting the central nervous system, peripheral nervous system and skeletal muscles, including anosmia and ageusia. The skin, the kidneys, the liver, the endocrine organs and the eyes are also affected by the systemic COVID-19 disease. Herein, we provide a comprehensive overview of the organ-specific systemic manifestations of COVID-19.
CRS and ICANS. Cardiac toxicities have ranged from tachycardia, dysrhythmias, heart block, and de... more CRS and ICANS. Cardiac toxicities have ranged from tachycardia, dysrhythmias, heart block, and decreased ejection fraction. However, in this case, severe ICANS led to severe autonomic neuropathy. First, the patient experienced severe bradycardia and eventually asystole, likely as a result of high parasympathetic stimulation from a disrupted BBB. 4 Later, the patient had hypertensive emergency as a result of an overactive sympathetic system from the disrupted BBB. Autonomic neuropathy as a manifestation of ICANS from CAR-T therapy has not been reported in the literature. Furthermore, ICANS is most commonly reversible unless seizures have occurred or fulminant cerebral edema. 1 Our patient suffered from irreversible neurotoxicity with short-term memory loss, disorientation, and confusion without any precedent seizure or cerebral edema. Lower platelet counts upon CART infusion, 5,6 high disease burden, and high-grade CRS are associated with severe ICANS, as observed in our patient. 3 Vascular dysfunction, manifested by endothelial activation and systemic capillary leak with BBB disruption, could be the underlying mechanisms for development of neurotoxicity. 2,3 In conclusion, although CART therapy is effective for hematologic malignancies, it can be associated with long-term debilitating sequalae, at times irreversible undermining the curative intent of this cellular immunotherapy.
Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the ... more Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the optimization of our thromboprophylaxis practice necessary. This review aims to make clear the need for the development of more accurate risk assessment tools and means of thrombosis prevention. Current clinical practice is guided by available guidelines published by the IMWG in 2014, but the extent to which these are implemented is unclear. Recently, several groups developed clinical scores for thrombosis risk in MM in an attempt to improve risk stratification, but these have not been validated or used in clinical practice so far. Research in this field is increasingly focusing on understanding the unique coagulation profile of the MM patient, and data on potential biomarkers that accurately reflect hypercoagulability is emerging. Finally, promising evidence on the effectiveness of direct oral anticoagulants (DOACs) in the context of thrombosis prevention in MM patients is increasingly b...
Key Points There was no significant difference in response rates, PFS, or OS among patients that ... more Key Points There was no significant difference in response rates, PFS, or OS among patients that developed resistance to different lenalidomide doses. Longer duration of prior lenalidomide and a longer lenalidomide-free interval are associated with better outcomes with pomalidomide.
Introduction: Chemotherapy associated osteoporosis is a severe problem in patients with malignant... more Introduction: Chemotherapy associated osteoporosis is a severe problem in patients with malignant diseases as it increases the risk for fractures and deteriorates quality of life. There are very limited data in the literature for the effect of chemotherapy on bone metabolism of adult patients with Non-Hodgkin Lymphoma (NHL). Thus, there is lack of formal recommendation regarding bone investigations at baseline or prophylactic bone management during treatment administration. The aim of this study was to perform a thorough assessment of bone remodeling in newly diagnosed patients with NHL, prior and post chemotherapy administration, to provide insight on the mechanisms of bone loss in these patients. Methods : Patients with NHL who received frontline treatment were eligible for participation in this study. Exclusion criteria included patients with lymphoma bone-involvement or with known osteoporosis under medication, previous bone fractures, BMD T-scores 55 years compared to all other...
Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor protei... more Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding intermediaries, which are deposited in target tissues causing progressive organ damage. In all forms of amyloidosis, vital organs may fail; depending on the specific amyloidosis type, this may occur rapidly or progress slowly. Beyond therapies to reduce the precursor protein (chemotherapy for light chain [AL] amyloidosis, anti-inflammatory therapy in serum A amyloidosis [AA], and antisense RNA therapy in transthyretin amyloidosis [ATTR]), organ transplantation may also be a means to reduce amyloidogenic protein, e.g., in types of amyloidosis in which the variant precursor is produced by the liver. Heart transplantation is a life-saving approach to the treatment of patients with advanced cardiac amyloidosis; however, amyloidosis may still be considered a contraindication to the procedure despite data supporting improved outcomes,...
1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated ... more 1) Background: Soluble urokinase-type plasminogen activator receptor (suPAR) has been implicated in the pathogenesis of kidney disease in different disease settings. The aim of this study was to investigate a possible link between suPAR circulating levels and renal impairment (RI) in newly diagnosed patients with symptomatic multiple myeloma (NDMM) before and after frontline therapy with bortezomib-based regimens. (2) Methods: We studied 47 NDMM patients (57% males, median age 69.5 years) before the administration of anti-myeloma treatment and at best response to bortezomib-based therapy. suPAR was measured in the serum of all patients and of 24 healthy matched controls, using an immuno-enzymatic assay (ViroGates, Denmark). (3) Results: suPAR levels were elevated in NDMM patients at diagnosis compared to healthy individuals (p < 0.001). suPAR levels strongly correlated with disease stage (p-ANOVA < 0.001). suPAR levels both at diagnosis and at best response negatively correlated with estimated glomerular filtration rate (eGFR) values (p < 0.001). Interestingly, no significance changes in suPAR levels were observed at best response compared to baseline values (p = 0.31) among 18 responding patients with baseline eGFR < 50 mL/min/1.73 m 2 . (4) Conclusions: SuPAR levels reflect renal function in NDMM patients treated with bortezomib-based induction. Responders may have elevated circulating suPAR levels, possibly reflecting persistent kidney damage, despite their renal response.
Although COVID-19 presents primarily as a lower respiratory tract infection transmitted via air d... more Although COVID-19 presents primarily as a lower respiratory tract infection transmitted via air droplets, increasing data suggest multiorgan involvement in patients that are infected. This systemic involvement is postulated to be mainly related to the SARS-CoV-2 virus binding on angiotensin-converting enzyme 2 (ACE2) receptors located on several different human cells. Lung involvement is the most common serious manifestation of the disease, ranging from asymptomatic disease or mild pneumonia, to severe disease associated with hypoxia, critical disease associated with shock, respiratory failure and multiorgan failure or death. Among patients with COVID-19, underlying cardiovascular comorbidities including hypertension, diabetes and especially cardiovascular disease, has been associated with adverse outcomes, whereas the emergence of cardiovascular complications, including myocardial injury, heart failure and arrhythmias, has been associated with poor survival. Gastrointestinal symptoms are also frequently encountered and may persist for several days. Haematological complications are frequent as well and have been associated with poor prognosis. Furthermore, recent studies have reported that over a third of infected patients develop a broad spectrum of neurological symptoms affecting the central nervous system, peripheral nervous system and skeletal muscles, including anosmia and ageusia. The skin, the kidneys, the liver, the endocrine organs and the eyes are also affected by the systemic COVID-19 disease. Herein, we provide a comprehensive overview of the organ-specific systemic manifestations of COVID-19.
CRS and ICANS. Cardiac toxicities have ranged from tachycardia, dysrhythmias, heart block, and de... more CRS and ICANS. Cardiac toxicities have ranged from tachycardia, dysrhythmias, heart block, and decreased ejection fraction. However, in this case, severe ICANS led to severe autonomic neuropathy. First, the patient experienced severe bradycardia and eventually asystole, likely as a result of high parasympathetic stimulation from a disrupted BBB. 4 Later, the patient had hypertensive emergency as a result of an overactive sympathetic system from the disrupted BBB. Autonomic neuropathy as a manifestation of ICANS from CAR-T therapy has not been reported in the literature. Furthermore, ICANS is most commonly reversible unless seizures have occurred or fulminant cerebral edema. 1 Our patient suffered from irreversible neurotoxicity with short-term memory loss, disorientation, and confusion without any precedent seizure or cerebral edema. Lower platelet counts upon CART infusion, 5,6 high disease burden, and high-grade CRS are associated with severe ICANS, as observed in our patient. 3 Vascular dysfunction, manifested by endothelial activation and systemic capillary leak with BBB disruption, could be the underlying mechanisms for development of neurotoxicity. 2,3 In conclusion, although CART therapy is effective for hematologic malignancies, it can be associated with long-term debilitating sequalae, at times irreversible undermining the curative intent of this cellular immunotherapy.
Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the ... more Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the optimization of our thromboprophylaxis practice necessary. This review aims to make clear the need for the development of more accurate risk assessment tools and means of thrombosis prevention. Current clinical practice is guided by available guidelines published by the IMWG in 2014, but the extent to which these are implemented is unclear. Recently, several groups developed clinical scores for thrombosis risk in MM in an attempt to improve risk stratification, but these have not been validated or used in clinical practice so far. Research in this field is increasingly focusing on understanding the unique coagulation profile of the MM patient, and data on potential biomarkers that accurately reflect hypercoagulability is emerging. Finally, promising evidence on the effectiveness of direct oral anticoagulants (DOACs) in the context of thrombosis prevention in MM patients is increasingly b...
Key Points There was no significant difference in response rates, PFS, or OS among patients that ... more Key Points There was no significant difference in response rates, PFS, or OS among patients that developed resistance to different lenalidomide doses. Longer duration of prior lenalidomide and a longer lenalidomide-free interval are associated with better outcomes with pomalidomide.
Introduction: Chemotherapy associated osteoporosis is a severe problem in patients with malignant... more Introduction: Chemotherapy associated osteoporosis is a severe problem in patients with malignant diseases as it increases the risk for fractures and deteriorates quality of life. There are very limited data in the literature for the effect of chemotherapy on bone metabolism of adult patients with Non-Hodgkin Lymphoma (NHL). Thus, there is lack of formal recommendation regarding bone investigations at baseline or prophylactic bone management during treatment administration. The aim of this study was to perform a thorough assessment of bone remodeling in newly diagnosed patients with NHL, prior and post chemotherapy administration, to provide insight on the mechanisms of bone loss in these patients. Methods : Patients with NHL who received frontline treatment were eligible for participation in this study. Exclusion criteria included patients with lymphoma bone-involvement or with known osteoporosis under medication, previous bone fractures, BMD T-scores 55 years compared to all other...
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