Marny Fedrigo - Academia.edu (original) (raw)
Papers by Marny Fedrigo
Italian Journal of Medicine, Jun 18, 2019
Amyloidosis is a group of progressive and devastating disorders resulting from misfolded proteins... more Amyloidosis is a group of progressive and devastating disorders resulting from misfolded proteins extracellular deposition into tissues. When deposition of fibrils occurs in cardiac tissues, this systemic disease can lead to a very poor prognosis. In this review, we focused on the most common types of cardiac amyloidosis and their treatments. Early diagnosis remains critically important, and here we reviewed the diagnostic methods adopted starting from the non-invasive imaging techniques to more invasive approaches, and the typing of precursor proteins. Typing the different misfolding proteins is mandatory since therapy differs accordingly and thus guiding therapy. We highlighted the most updated and recent treatment strategies to cure amyloidosis.
Journal of Heart and Lung Transplantation, Apr 1, 2019
Purpose: In heart and kidney transplants, rejection is a major cause of graft loss. In kidneys, a... more Purpose: In heart and kidney transplants, rejection is a major cause of graft loss. In kidneys, antibody-mediated rejection (ABMR) is more important than T cell-mediated rejection (TCMR), and molecules predict graft loss better than histology (JASN 26 (7):1711(JASN 26 (7): -1720(JASN 26 (7): , 2015)). We examined the relative importance of ABMR vs TCMR in heart transplant endomyocardial biopsies (EMBs), and the molecules predicting graft survival. Methods: The INTERHEART population includes 1219 transplant biopsies from 8 centers in Canada, USA, Australia and Europe. Gene expression was studied using microarrays, selecting the most recent biopsy per patient. Random forest classifiers were used to assess predictive accuracy and determine the importance of molecular predictors, including gene sets and scores from analyses in a reference set of 889 EMBs. Results: We studied 3-year survival in 484 patients with follow-up times. Graft failure occurred in 60 patients. Median follow-up was 435 days; biopsies were mainly for indications. Surprisingly, TCMR was a greater short-term hazard than ABMR. The molecular archetype clusters for TCMR and injury (Fig. ) had the highest risk of graft failure. Fig. combines these clusters since they have similar characteristics. Conclusion: Unlike kidneys, graft loss (particularly within one year) after EMB is highly associated with TCMR but not ABMR. TCMR may reflect failure of immunosuppression or non-adherence. This difference between the heart and renal transplant populations raises the possibility that TCMR is relatively more destructive, and ABMR less destructive, in heart than in kidney transplants. ClinicalTrials.gov # NCT02670408 105 miR-208a-5p and miR-135a-5p in Formalin Fixed Paraffin Embedded
Frontiers in Immunology, May 15, 2023
Background: Antibody-mediated rejection (AMR) is a serious complication affecting the survival of... more Background: Antibody-mediated rejection (AMR) is a serious complication affecting the survival of patients receiving transplantation. Human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common viral infections that occur after transplantation, frequently emerging as viral reactivation in donor grafts or transplant recipients. The present study aimed to investigate the association between CMV and EBV infections and early-onset AMR. Materials and methods: This study was conducted at the Heart Transplantation Center of Padova General Hospital and included a cohort of 47 heart transplant recipients (HTxs), including 24 HTxs diagnosed with AMR and 23 control HTxs with no episodes of AMR. Only early cases of CMV and/or EBV infections (1-90 days after transplantation) were considered. Fisher's exact test and logistic regression analysis were used to statistically analyze the correlation and association between AMR and CMV or EBV infection. We observed a positive statistical association between CMV and EBV infections (two-sided Fisher's exact test, p = 0.0136) and between EBV infection and AMR (two-sided Fisher's exact test, p = 0.0034). Logistic regression analysis Frontiers in Immunology frontiersin.org 01
Viruses, Dec 30, 2022
The present study aims to provide the sequential immunological, clinical and virological events o... more The present study aims to provide the sequential immunological, clinical and virological events occurring in a CMV-infected pregnant woman experiencing intrauterine CMV transmission. In brief, a case of primary CMV infection occurred in a 36-year-old pregnant woman. The patient exhibited early-sustained viremia and viruria, detectable presence of CMV in saliva concomitant with a strong CMV-specific cell-mediated response (427 EliSpots). CMV was detected in the amniotic fluid at 15 weeks of pregnancy (>1 × 10 6 CMV copies/mL). The pregnancy was deliberately interrupted at 16 weeks of gestation. Fetal histological and pathological examinations revealed placentitis and fetal brain alterations as microcephaly and cortical dysplasia. Interestingly, this clinical report shows: (1) there was a rapid and sustained CMV-specific cell mediated immune response (Th1) in association with low IgG avidity (Th2) correlated with fetal CMV transmission. (2) The levels of CMV-specific cell-mediated immune response persisted at high levels up to 200 weeks after infection despite clinical and viral clearance. (3) The histological and pathological evidence suggests that a potent pro-inflammatory condition at the placental level may lead to cCMV.
Leukemia & Lymphoma, Sep 10, 2019
Journal of Heart and Lung Transplantation, Apr 1, 2016
Purpose: Left ventricular assist devices (LVADs) are increasingly used in long-term therapy. At t... more Purpose: Left ventricular assist devices (LVADs) are increasingly used in long-term therapy. At the time of transplantation or death, we can assess the effect of device on cardiac structural changes. In our experience, we noted aortic valve (AV) commissure fusion. We hypothesize that the preservation of aortic valve opening prevents fusion and consequent valveincompetence. Methods: We examined 29 hearts (explants and autopsy specimens) from patients supported with Jarvik 2000 ILS (intermittent low speed) (n= 11) that allows the opening of the native AV for 8 seconds every 64, and should, theoretically, preserve the native AV, or with Heartware HVAD (n= 17). We noted commissures involved, fusion length (mm), duration of LVAD support, and type of LVAD. As controls, we examined 20 explanted hearts from patients with heart failure who were not supported by LVADs. Results: Median duration of the assistance was 144 days (range: 12-1147 days); 433±401 days for Jarvik 2000 and 154±136 days for Heartware. Nine patients (31%) had some degree of native AV commissural fusion (4 Jarvik 2000: 44.4%; 5 Heartware: 55%). Four patients (44.4%) had fusion at 1 commissure (2 Jarvik 2000 and 2 Heartware); two patients (22.2%) at 2 commissures (1 Jarvik 2000 and 1 Heartware); three patients (33.3%) at 3 commissures (1 Jarvik 2000 and 2 Heartware). Additionally, we observed 6 hearts (66.7%) with cusp prolapse (5 Jarvik 2000: 83%; 1 Heartware: 17%). Four patients (66.6%) had prolapse of one cusp (4 Jarvik 2000) and two patients (33.4%) of 2 cusps (1 Jarvik 2000 and 1 Heartware). Four patients (66.6%) presented non-coronary-cusp prolapse associated in three cases with non-coronary-sinus dilation. One single patient assisted with the Jarvik 2000 and prolapse of 2 cusps had clinically significant native AV insufficiency, with necessity of changing the controller ILS provided with one without the reduction of the speed, because of haemodynamic intolerance. No patient with commissural fusion required increased LVAD support. Conclusion: Acquired commissural fusion is common in patients supported by LVADs. The cyclic opening of the AV may delay this process. Furthermore, we observed incidence of cusp-prolapse. The clinical significance of the two substrates in our population was almost absent.
Circulation, Nov 26, 2013
Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic ... more Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic Heart Failure (CHF). The mechanisms leading to kidney damage in CHF are however still obscure. We st...
European Heart Journal, Aug 2, 2013
Background: Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence... more Background: Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic Heart Failure (CHF). The mechanisms leading to kidney damage in CHF are however still obscure.We studied the development of kidney injury in a model of right CHF (monocrotaline (MC) treated rats). Methods: 10 animals were treated with MC for 4 weeks until they developed HF. 11 were taken as control. The occurrence of HF wasdemonstrated by signs of congestion, hypertrophy and dilatation of the right ventricle, and by the determination of BNP. We measured pNGAL, pCreatinine (ELISA), kidney NGAL (RT-PCR), and pTNFα, IL1, IL4, IL6, IL10 (Multiplex protein microarray). Kidney cell apoptosis was assessed by TUNEL. Results: MC treated rats showed higher BNP values (MC 4.7±1.2, C 1.5±0.5 pg/mL p<0.004), marked RV Hypetrophy and dilatation (RVMass/RVVolume
Many different noxae can affect the cardiac allograft prior to transplantation in relation to don... more Many different noxae can affect the cardiac allograft prior to transplantation in relation to donor type or mode of death, donor management in Intensive Care Unit, during graft procurement and surgical procedure, and immediately after transplantation due to recipient’s general condition. All these can injure the graft and cause lesions comprehensively known as perioperative myocardial damage to the graft. This chapter summarizes the main histopathological substrates related to perioperative injury, which can be encountered at endomyocardial biopsy evaluation up to 6 weeks after transplantation or at autopsy after early death.
Journal of Heart and Lung Transplantation, Apr 1, 2012
Purpose: Diagnosis of antibody-mediated rejection (AMR) is still a matter of controversial discus... more Purpose: Diagnosis of antibody-mediated rejection (AMR) is still a matter of controversial discussion. We suggested that immunoglobulin staining might improve the diagnostic spectrum of AMR because of seasonal effects in complement deposition. We studied prospectively all endomyocardial biopsies harvested since 01/2011 (nϭ205) for acute cellular rejection (ISHLT), endothelial swelling and microvascular deposition of C4d, C3d and IgA/M/G in paraffin sections (immunohistochemistry). Pathologic and immunopathologic AMR findings were classified according to the ISHLT and studied for seasonal effects in an ordinal (Jan-Mar vs. Apr-Jun vs. Jul-Sept vs. Oct-Dec) and nominal model (Oct-Mar vs. Apr-Sept). Results: Overall, 16% of biopsies showed signs of acute cellular rejection of any grade and 46% of samples showed evidence of endothelial swelling. In the ordinal model (Jan-Mar vs. Apr-Jun vs. Jul-Sep vs. Oct-Dec), seasonal effects were found for endothelial swelling (83% vs. 14% vs. 49% vs. 40%; pϽ0.001), IgA deposition (62% vs. 71% vs. 86% vs. 92%; pϭ0.046), C4d deposition (36% vs. 9% vs. 20% vs. 15%; pϭ0.003) and C4d deposition in combination with endothelial swelling (35% vs. 5% vs. 9% vs. 4%; pϽ0.001). In the nominal model (Oct-Mar vs. Apr-Sep) we found similar results showing seasonal effects for endothelial swelling (70% vs. 30%; pϽ0.001), C4d deposition (29% vs. 14%; pϭ0.012) and C4d deposition in combination with endothelial swelling (25% vs. 7%; pϽ0.001). No other combinations of histopathology or immunopathology or acute cellular rejection showed seasonal behavior. AMR according to the ISHLT was not associated with impaired graft function in echocardiography. Conclusions: Complement deposition seems to be more pronounced in autumn and winter. IgA deposition might add important information about coincident alloimmune responses derived from mucosal surfaces and might be considered to complement current diagnostic parameters.
Journal of Heart and Lung Transplantation, Apr 1, 2019
Purpose: Creation of bioengineered lungs (BL) through decellularization of porcine lungs followed... more Purpose: Creation of bioengineered lungs (BL) through decellularization of porcine lungs followed by recellularization of the scaffold with human cells has been identified as a promising strategy for increasing the number of lungs suitable for transplant. Here, we report our progress developing a BL based on this combination decell/recell strategy. Methods: Left lungs were dissected from porcine heart-lung blocks and decellularized. The left main pulmonary artery (PA), left atrial cuff (LA), and left main bronchus were then cannulated and attached to a bioreactor. Epithelial cells (EP) were instilled into the airway, followed by instillation of endothelial cells (EC) through the PA and LA. The grafts were then cultured for 7 to 16 days, followed by functional assessment by modified ex vivo lung perfusion (EVLP) techniques. Mock recells (MR) were also performed using the same dissection and perfusion scheme, but seeding steps were also omitted. Results: After recellularization, 42 BLs received functional evaluation. Overall, the mean DPaO 2 /FiO 2 ratio of BLs was 233 mmHg (Figure ), compared to an average of 102mmHg for MR and 395 mmHg for native porcine lungs (NL). Tidal volume and PIP in BL averaged 42ml and 24 cmH 2 O, respectively, compared to 25ml and 23 cmH 2 O in MR and 93ml and 17 cmH 2 O in NL. Additionally, vascular resistance (VR) in BL averaged 18,040 dyn*s*cm -5 at an average PA pressure (PAP) of 9 mmHg (Figure ). This was higher than decellularized scaffold, which averaged 17,600 dyn*s*cm -5 at 6 mmHg and NL, which averaged 3960 dyn*s*cm -5 at an average PAP of 17 mmHg. Conclusion: We report positive progress toward production of functional BL grafts. Our results detail BL grafts that have perfusable vasculature and are capable of moderate gas exchange. While more development is required, considerable progress has been made, bringing bioengineered lungs closer to reality.
Hematological Oncology, Oct 3, 2017
Light chain amyloidosis is characterized by the progressive deposition of immunoglobulin light ch... more Light chain amyloidosis is characterized by the progressive deposition of immunoglobulin light chains into the extracellular tissue, leading to organ dysfunction. Usually, it is associated with an underlying clonal plasma cell dyscrasia and rarely with chronic lymphocytic leukaemia. Herein, we described the first report of a patient with relapsed chronic lymphocytic leukaemia harbouring TP53 abnormalities who developed, histologically proven, systemic light chain amyloidosis who was treated with the PI3K inhibitor, idelalisib, and rituximab. Unfortunately, the patient had sudden death during sleep, likely caused by arrhythmia secondary to amyloid cardiomyopathy. Idelalisib was at least effective in reducing secretory free light chain, chronic lymphocytic leukaemia burden, and to improve the survival of patient. Systemic light chain amyloidosis (AL) is characterized by the extracellu-
Circulation-heart Failure, Nov 1, 2015
Journal of The Peripheral Nervous System, Mar 10, 2023
Nephrology Dialysis Transplantation, May 1, 2021
BACKGROUND AND AIMS: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome i... more BACKGROUND AND AIMS: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in older white adults, with an incidence of 12 cases per millions of people per year. Primary MN (PMN, 75%-80% of MNs) is an organ-specific autoimmune disease caused by antibodies anti-PLA2R and anti-THSD7A. Regardless of treatment one third of patients progresses to end-stage renal disease and two third Nephrology Dialysis Transplantation
Journal of Cardiac Surgery, Sep 29, 2021
Circumferential calcification of the ascending aorta, known as porcelain aorta, in a patient cand... more Circumferential calcification of the ascending aorta, known as porcelain aorta, in a patient candidate to a heart transplant, requires technically demanding and high‐risk procedural adjustments.
Pediatric Transplantation, May 4, 2018
Italian Journal of Medicine, Jun 18, 2019
Amyloidosis is a group of progressive and devastating disorders resulting from misfolded proteins... more Amyloidosis is a group of progressive and devastating disorders resulting from misfolded proteins extracellular deposition into tissues. When deposition of fibrils occurs in cardiac tissues, this systemic disease can lead to a very poor prognosis. In this review, we focused on the most common types of cardiac amyloidosis and their treatments. Early diagnosis remains critically important, and here we reviewed the diagnostic methods adopted starting from the non-invasive imaging techniques to more invasive approaches, and the typing of precursor proteins. Typing the different misfolding proteins is mandatory since therapy differs accordingly and thus guiding therapy. We highlighted the most updated and recent treatment strategies to cure amyloidosis.
Journal of Heart and Lung Transplantation, Apr 1, 2019
Purpose: In heart and kidney transplants, rejection is a major cause of graft loss. In kidneys, a... more Purpose: In heart and kidney transplants, rejection is a major cause of graft loss. In kidneys, antibody-mediated rejection (ABMR) is more important than T cell-mediated rejection (TCMR), and molecules predict graft loss better than histology (JASN 26 (7):1711(JASN 26 (7): -1720(JASN 26 (7): , 2015)). We examined the relative importance of ABMR vs TCMR in heart transplant endomyocardial biopsies (EMBs), and the molecules predicting graft survival. Methods: The INTERHEART population includes 1219 transplant biopsies from 8 centers in Canada, USA, Australia and Europe. Gene expression was studied using microarrays, selecting the most recent biopsy per patient. Random forest classifiers were used to assess predictive accuracy and determine the importance of molecular predictors, including gene sets and scores from analyses in a reference set of 889 EMBs. Results: We studied 3-year survival in 484 patients with follow-up times. Graft failure occurred in 60 patients. Median follow-up was 435 days; biopsies were mainly for indications. Surprisingly, TCMR was a greater short-term hazard than ABMR. The molecular archetype clusters for TCMR and injury (Fig. ) had the highest risk of graft failure. Fig. combines these clusters since they have similar characteristics. Conclusion: Unlike kidneys, graft loss (particularly within one year) after EMB is highly associated with TCMR but not ABMR. TCMR may reflect failure of immunosuppression or non-adherence. This difference between the heart and renal transplant populations raises the possibility that TCMR is relatively more destructive, and ABMR less destructive, in heart than in kidney transplants. ClinicalTrials.gov # NCT02670408 105 miR-208a-5p and miR-135a-5p in Formalin Fixed Paraffin Embedded
Frontiers in Immunology, May 15, 2023
Background: Antibody-mediated rejection (AMR) is a serious complication affecting the survival of... more Background: Antibody-mediated rejection (AMR) is a serious complication affecting the survival of patients receiving transplantation. Human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are common viral infections that occur after transplantation, frequently emerging as viral reactivation in donor grafts or transplant recipients. The present study aimed to investigate the association between CMV and EBV infections and early-onset AMR. Materials and methods: This study was conducted at the Heart Transplantation Center of Padova General Hospital and included a cohort of 47 heart transplant recipients (HTxs), including 24 HTxs diagnosed with AMR and 23 control HTxs with no episodes of AMR. Only early cases of CMV and/or EBV infections (1-90 days after transplantation) were considered. Fisher's exact test and logistic regression analysis were used to statistically analyze the correlation and association between AMR and CMV or EBV infection. We observed a positive statistical association between CMV and EBV infections (two-sided Fisher's exact test, p = 0.0136) and between EBV infection and AMR (two-sided Fisher's exact test, p = 0.0034). Logistic regression analysis Frontiers in Immunology frontiersin.org 01
Viruses, Dec 30, 2022
The present study aims to provide the sequential immunological, clinical and virological events o... more The present study aims to provide the sequential immunological, clinical and virological events occurring in a CMV-infected pregnant woman experiencing intrauterine CMV transmission. In brief, a case of primary CMV infection occurred in a 36-year-old pregnant woman. The patient exhibited early-sustained viremia and viruria, detectable presence of CMV in saliva concomitant with a strong CMV-specific cell-mediated response (427 EliSpots). CMV was detected in the amniotic fluid at 15 weeks of pregnancy (>1 × 10 6 CMV copies/mL). The pregnancy was deliberately interrupted at 16 weeks of gestation. Fetal histological and pathological examinations revealed placentitis and fetal brain alterations as microcephaly and cortical dysplasia. Interestingly, this clinical report shows: (1) there was a rapid and sustained CMV-specific cell mediated immune response (Th1) in association with low IgG avidity (Th2) correlated with fetal CMV transmission. (2) The levels of CMV-specific cell-mediated immune response persisted at high levels up to 200 weeks after infection despite clinical and viral clearance. (3) The histological and pathological evidence suggests that a potent pro-inflammatory condition at the placental level may lead to cCMV.
Leukemia & Lymphoma, Sep 10, 2019
Journal of Heart and Lung Transplantation, Apr 1, 2016
Purpose: Left ventricular assist devices (LVADs) are increasingly used in long-term therapy. At t... more Purpose: Left ventricular assist devices (LVADs) are increasingly used in long-term therapy. At the time of transplantation or death, we can assess the effect of device on cardiac structural changes. In our experience, we noted aortic valve (AV) commissure fusion. We hypothesize that the preservation of aortic valve opening prevents fusion and consequent valveincompetence. Methods: We examined 29 hearts (explants and autopsy specimens) from patients supported with Jarvik 2000 ILS (intermittent low speed) (n= 11) that allows the opening of the native AV for 8 seconds every 64, and should, theoretically, preserve the native AV, or with Heartware HVAD (n= 17). We noted commissures involved, fusion length (mm), duration of LVAD support, and type of LVAD. As controls, we examined 20 explanted hearts from patients with heart failure who were not supported by LVADs. Results: Median duration of the assistance was 144 days (range: 12-1147 days); 433±401 days for Jarvik 2000 and 154±136 days for Heartware. Nine patients (31%) had some degree of native AV commissural fusion (4 Jarvik 2000: 44.4%; 5 Heartware: 55%). Four patients (44.4%) had fusion at 1 commissure (2 Jarvik 2000 and 2 Heartware); two patients (22.2%) at 2 commissures (1 Jarvik 2000 and 1 Heartware); three patients (33.3%) at 3 commissures (1 Jarvik 2000 and 2 Heartware). Additionally, we observed 6 hearts (66.7%) with cusp prolapse (5 Jarvik 2000: 83%; 1 Heartware: 17%). Four patients (66.6%) had prolapse of one cusp (4 Jarvik 2000) and two patients (33.4%) of 2 cusps (1 Jarvik 2000 and 1 Heartware). Four patients (66.6%) presented non-coronary-cusp prolapse associated in three cases with non-coronary-sinus dilation. One single patient assisted with the Jarvik 2000 and prolapse of 2 cusps had clinically significant native AV insufficiency, with necessity of changing the controller ILS provided with one without the reduction of the speed, because of haemodynamic intolerance. No patient with commissural fusion required increased LVAD support. Conclusion: Acquired commissural fusion is common in patients supported by LVADs. The cyclic opening of the AV may delay this process. Furthermore, we observed incidence of cusp-prolapse. The clinical significance of the two substrates in our population was almost absent.
Circulation, Nov 26, 2013
Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic ... more Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic Heart Failure (CHF). The mechanisms leading to kidney damage in CHF are however still obscure. We st...
European Heart Journal, Aug 2, 2013
Background: Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence... more Background: Cardiorenal Syndrome Type II (CRSII) is kidney function deterioration in the presence of Chronic Heart Failure (CHF). The mechanisms leading to kidney damage in CHF are however still obscure.We studied the development of kidney injury in a model of right CHF (monocrotaline (MC) treated rats). Methods: 10 animals were treated with MC for 4 weeks until they developed HF. 11 were taken as control. The occurrence of HF wasdemonstrated by signs of congestion, hypertrophy and dilatation of the right ventricle, and by the determination of BNP. We measured pNGAL, pCreatinine (ELISA), kidney NGAL (RT-PCR), and pTNFα, IL1, IL4, IL6, IL10 (Multiplex protein microarray). Kidney cell apoptosis was assessed by TUNEL. Results: MC treated rats showed higher BNP values (MC 4.7±1.2, C 1.5±0.5 pg/mL p<0.004), marked RV Hypetrophy and dilatation (RVMass/RVVolume
Many different noxae can affect the cardiac allograft prior to transplantation in relation to don... more Many different noxae can affect the cardiac allograft prior to transplantation in relation to donor type or mode of death, donor management in Intensive Care Unit, during graft procurement and surgical procedure, and immediately after transplantation due to recipient’s general condition. All these can injure the graft and cause lesions comprehensively known as perioperative myocardial damage to the graft. This chapter summarizes the main histopathological substrates related to perioperative injury, which can be encountered at endomyocardial biopsy evaluation up to 6 weeks after transplantation or at autopsy after early death.
Journal of Heart and Lung Transplantation, Apr 1, 2012
Purpose: Diagnosis of antibody-mediated rejection (AMR) is still a matter of controversial discus... more Purpose: Diagnosis of antibody-mediated rejection (AMR) is still a matter of controversial discussion. We suggested that immunoglobulin staining might improve the diagnostic spectrum of AMR because of seasonal effects in complement deposition. We studied prospectively all endomyocardial biopsies harvested since 01/2011 (nϭ205) for acute cellular rejection (ISHLT), endothelial swelling and microvascular deposition of C4d, C3d and IgA/M/G in paraffin sections (immunohistochemistry). Pathologic and immunopathologic AMR findings were classified according to the ISHLT and studied for seasonal effects in an ordinal (Jan-Mar vs. Apr-Jun vs. Jul-Sept vs. Oct-Dec) and nominal model (Oct-Mar vs. Apr-Sept). Results: Overall, 16% of biopsies showed signs of acute cellular rejection of any grade and 46% of samples showed evidence of endothelial swelling. In the ordinal model (Jan-Mar vs. Apr-Jun vs. Jul-Sep vs. Oct-Dec), seasonal effects were found for endothelial swelling (83% vs. 14% vs. 49% vs. 40%; pϽ0.001), IgA deposition (62% vs. 71% vs. 86% vs. 92%; pϭ0.046), C4d deposition (36% vs. 9% vs. 20% vs. 15%; pϭ0.003) and C4d deposition in combination with endothelial swelling (35% vs. 5% vs. 9% vs. 4%; pϽ0.001). In the nominal model (Oct-Mar vs. Apr-Sep) we found similar results showing seasonal effects for endothelial swelling (70% vs. 30%; pϽ0.001), C4d deposition (29% vs. 14%; pϭ0.012) and C4d deposition in combination with endothelial swelling (25% vs. 7%; pϽ0.001). No other combinations of histopathology or immunopathology or acute cellular rejection showed seasonal behavior. AMR according to the ISHLT was not associated with impaired graft function in echocardiography. Conclusions: Complement deposition seems to be more pronounced in autumn and winter. IgA deposition might add important information about coincident alloimmune responses derived from mucosal surfaces and might be considered to complement current diagnostic parameters.
Journal of Heart and Lung Transplantation, Apr 1, 2019
Purpose: Creation of bioengineered lungs (BL) through decellularization of porcine lungs followed... more Purpose: Creation of bioengineered lungs (BL) through decellularization of porcine lungs followed by recellularization of the scaffold with human cells has been identified as a promising strategy for increasing the number of lungs suitable for transplant. Here, we report our progress developing a BL based on this combination decell/recell strategy. Methods: Left lungs were dissected from porcine heart-lung blocks and decellularized. The left main pulmonary artery (PA), left atrial cuff (LA), and left main bronchus were then cannulated and attached to a bioreactor. Epithelial cells (EP) were instilled into the airway, followed by instillation of endothelial cells (EC) through the PA and LA. The grafts were then cultured for 7 to 16 days, followed by functional assessment by modified ex vivo lung perfusion (EVLP) techniques. Mock recells (MR) were also performed using the same dissection and perfusion scheme, but seeding steps were also omitted. Results: After recellularization, 42 BLs received functional evaluation. Overall, the mean DPaO 2 /FiO 2 ratio of BLs was 233 mmHg (Figure ), compared to an average of 102mmHg for MR and 395 mmHg for native porcine lungs (NL). Tidal volume and PIP in BL averaged 42ml and 24 cmH 2 O, respectively, compared to 25ml and 23 cmH 2 O in MR and 93ml and 17 cmH 2 O in NL. Additionally, vascular resistance (VR) in BL averaged 18,040 dyn*s*cm -5 at an average PA pressure (PAP) of 9 mmHg (Figure ). This was higher than decellularized scaffold, which averaged 17,600 dyn*s*cm -5 at 6 mmHg and NL, which averaged 3960 dyn*s*cm -5 at an average PAP of 17 mmHg. Conclusion: We report positive progress toward production of functional BL grafts. Our results detail BL grafts that have perfusable vasculature and are capable of moderate gas exchange. While more development is required, considerable progress has been made, bringing bioengineered lungs closer to reality.
Hematological Oncology, Oct 3, 2017
Light chain amyloidosis is characterized by the progressive deposition of immunoglobulin light ch... more Light chain amyloidosis is characterized by the progressive deposition of immunoglobulin light chains into the extracellular tissue, leading to organ dysfunction. Usually, it is associated with an underlying clonal plasma cell dyscrasia and rarely with chronic lymphocytic leukaemia. Herein, we described the first report of a patient with relapsed chronic lymphocytic leukaemia harbouring TP53 abnormalities who developed, histologically proven, systemic light chain amyloidosis who was treated with the PI3K inhibitor, idelalisib, and rituximab. Unfortunately, the patient had sudden death during sleep, likely caused by arrhythmia secondary to amyloid cardiomyopathy. Idelalisib was at least effective in reducing secretory free light chain, chronic lymphocytic leukaemia burden, and to improve the survival of patient. Systemic light chain amyloidosis (AL) is characterized by the extracellu-
Circulation-heart Failure, Nov 1, 2015
Journal of The Peripheral Nervous System, Mar 10, 2023
Nephrology Dialysis Transplantation, May 1, 2021
BACKGROUND AND AIMS: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome i... more BACKGROUND AND AIMS: Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in older white adults, with an incidence of 12 cases per millions of people per year. Primary MN (PMN, 75%-80% of MNs) is an organ-specific autoimmune disease caused by antibodies anti-PLA2R and anti-THSD7A. Regardless of treatment one third of patients progresses to end-stage renal disease and two third Nephrology Dialysis Transplantation
Journal of Cardiac Surgery, Sep 29, 2021
Circumferential calcification of the ascending aorta, known as porcelain aorta, in a patient cand... more Circumferential calcification of the ascending aorta, known as porcelain aorta, in a patient candidate to a heart transplant, requires technically demanding and high‐risk procedural adjustments.
Pediatric Transplantation, May 4, 2018