Chronic Pulmonary Silicone Embolism from Breast Augmentation Is Not a Common Finding in Explanted Lungs

Objective. Acute pulmonary silicone embolism (APSE) related to subcutaneous silicone injections is a well-known entity. Recently, a few cases of pathologically confirmed chronic pulmonary silicone embolism (CPSE) from breast implants have been reported. The prevalence of CPSE in women with breast augmentation is unknown. This study was done to determine the prevalence of CPSE in female lung transplant recipients with a history of breast augmentation and to determine whether breast augmentation plays a role in chronic lung diseases requiring lung transplantation. Methods. A retrospective chart review was performed to identify female lung transplant recipients with a history of breast augmentation prior to or at the time of lung transplantation. Ten patients meeting these criteria were identified. The pathologic features of the explanted lungs of these patients were reexamined for CPSE by a board-certified pathologist with expertise in lung transplantation and pulmonary embolism. Results. Of 1518 lung transplant recipients at Cleveland Clinic, 578 were females. Of 578 females, 10 (1.73%) had history of breast augmentation. A total of 84 H&E-stained slides from the explanted lungs from 10 cases were examined. No pathologic evidence of chronic silicone embolism was seen in any of the 10 cases. Conclusions. CPSE is not associated with pulmonary disease leading to lung transplantation. Breast augmentation is not a significant contributor to pulmonary disease requiring lung transplantation. Further studies are required to ascertain the prevalence of CPSE in the general breast augmentation populace and to define the relationship between breast augmentation and pulmonary disease.

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Multifactorial Hyponatremia in a Lung Transplant Recipient: A Case Report of Pseudohyponatremia, SIADH and Secondary Adrenal Insufficiency

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.290 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A143-A144

Author(s):

Rani Shayto

Keyword(s):

Abdominal Pain ◽

Transplant Recipient ◽

Lung Transplantation ◽

Lung Transplant ◽

Lymphoproliferative Disorders ◽

Lung Transplant Recipient ◽

Transplant Recipients ◽

History Of ◽

Lung Transplant Recipients ◽

Posttransplant Lymphoproliferative Disorders

Abstract Background: Lung transplant recipients are prone to developing multifactorial hyponatremia from immunosuppressive therapies and posttransplant lymphoproliferative disorders. Clinical Case: A 77-year-old male with a history of lung transplantation in 2017 presented for a 3-month history of confusion, decline in executive function and chronic abdominal pain. Vital signs were BP 137/81 mmHg, HR 81 bpm, RR 14 per minute, SPO2 99% and afebrile. The patient was clinically euvolemic with a presenting sodium was 129 mmol/L, and was treated with 2.5L IV 0.9% saline. Home immunosuppression with cyclosporine, azathioprine and prednisone 5 mg/d were continued. Sodium declined to 126 mmol/L on day 4 prompting endocrine consult. Labs prior to fluid administration were consistent with iso-osmolar hyponatremia: sOsm 283 mOsm/kg and uOsm 409 mOsm/kg. Pseudohyponatremia was suspected and electrophoresis and immunofixation revealed a free kappa light chain gammopathy. Evaluation when sodium was 126 mmol/L was now consistent with hypotonic hyponatremia: sOsm 273 mOsm/kg, uOsm 398 mOsm/kg, and urine sodium 56mmol/L. TSH was normal and AM cortisol was 11.9 ug/dL (3.7–19.4 ug/dL), drawn while on maintenance prednisone. Lab findings and improvement of abdominal pain after receiving high dose prednisone for CT contrast-allergy prophylaxis raised our suspicion for SIADH and undertreated secondary AI. Retrospective chart review revealed tacrolimus use after lung transplant before its discontinuation 9 months prior to admission. Chronic hyponatremia was noted a few months post lung transplantation, with a nadir of 120 mmol/L and only mild improvement despite tacrolimus discontinuation and empiric fludrocortisone use. The patient was treated with a 1L fluid restriction, doubling of prednisone to 10 mg/d and cessation of fludrocortisone for lack of concern for primary. Abdominal symptoms resolved, mental status improved, and serum sodium rose to 132 mmol/L over the next few days, later normalizing to 135–140 mmol/L on follow up. The patient was eventually diagnosed with Waldenström macroglobulinemia. Conclusion: Hyponatremia in lung transplant recipients can be multifactorial. Calcineurin inhibitors and steroids are part of typical immunosuppressive regimens and can lead to hyponatremia through salt wasting nephropathy or SIADH(1), and undertreated secondary AI, respectively. Posttransplant lymphoproliferative disorders occur in up to 9% of cases(2) and must be suspected as an etiology of hyponatremia. References: 1.Cowan AJ, Johnson CK, Libby EN. Plasma cell diseases and organ transplant: A comprehensive review. Am J Transplant. 2018;18(5):1046–58.2.Aris RM, Maia DM, Neuringer IP, Gott K, Kiley S, Gertis K, et al. Post-transplantation lymphoproliferative disorder in the Epstein-Barr virus-naïve lung transplant recipient. Am J Respir Crit Care Med. 1996;154(6 Pt 1):1712–7.

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Detrimental Association of Hypogammaglobulinemia With Chronic Lung Allograft Dysfunction and Death Is Not Mitigated by On-Demand Immunoglobulin G Replacement After Lung Transplantation

Progress in Transplantation ◽

10.1177/1526924818817028 ◽

2018 ◽

Vol 29 (1) ◽

pp. 18-25

Author(s):

Alicia B. Lichvar ◽

Christopher R. Ensor ◽

Adriana Zeevi ◽

Matthew R. Morrell ◽

Joseph M. Pilewski ◽

...

Keyword(s):

Lung Transplantation ◽

Immunoglobulin G ◽

Lung Transplant ◽

Primary Outcome ◽

Transplant Recipients ◽

Chronic Lung Allograft Dysfunction ◽

On Demand ◽

Allograft Dysfunction ◽

Group 2 ◽

Lung Transplant Recipients

Background: Hypogammaglobulinemia (HGG), immunoglobulin G (IgG) <700 mg/dL, is associated with infections, chronic lung allograft dysfunction, and death following lung transplantation. This study evaluates the use of on-demand intravenous IgG in lung transplant recipients with HGG. Materials and Methods: This single-center retrospective cohort study of adult lung recipients evaluated 3 groups, no, untreated (u), or treated (t) HGG at first IgG administration or a matched time posttransplant. Primary outcome was freedom from allograft dysfunction. Secondary outcomes included development of advanced dysfunction, rejection, infection burden, and mortality. Results: Recipients included 484 (no HGG: 76, uHGG: 192, tHGG: 216). Freedom from chronic allograph dysfunction was highest in the non-HGG group 2 years post-enrollment (no HGG 77.9% vs uHGG 56.4% vs tHGG 52.5%; P = .002). Freedom from advanced dysfunction was significantly different 2 years post-enrollment (no HGG 90.5% vs uHGG 84.7% vs tHGG 75.4%; P = .017). Patients without HGG and those with uHGG had less mortality at 2 years post-enrollment (no HGG 84.2% vs uHGG 81.3% vs tHGG 64.8%; P < .001). Gram-negative pneumonias occurred more often in the tHGG group ( P = .02). Conclusions: Development of chronic lung allograft dysfunction, patient survival, rejection burden, and key infectious outcomes in lung transplant recipients were still problematic in the context of on-demand IgG therapy. Prospective studies are warranted.

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Viral load Guided Immunosuppression after Lung Transplantation (VIGILung) – study protocol for a randomized controlled trial

10.21203/rs.3.rs-38454/v1 ◽

2020 ◽

Author(s):

Jens Gottlieb ◽

Alexander Reuss ◽

Konstantin Mayer ◽

Karin Weide ◽

Carmen Schade-Brittinger ◽

...

Keyword(s):

Therapeutic Drug Monitoring ◽

Lung Transplantation ◽

Drug Monitoring ◽

Lung Transplant ◽

Controlled Trial ◽

Therapeutic Drug ◽

Transplant Recipients ◽

Randomized Controlled ◽

Lung Transplant Recipients ◽

Trough Levels

Abstract Background:Immunosuppression including high dose calcineurin-inhibitors (CNI) is essential after lung transplantation. Dosing is usually guided by therapeutic drug monitoring adjusted to target trough levels of CNIs to keep the balance between over-dose causing severe toxicity and increased risk of infections or under-dose with risk of graft-injury.Adaptation of CNI-based immunosuppression by monitoring of Torque-Teno-Virus (TTV) – a latent nonpathogenic DNA virus, measured in whole blood in addition to conventional therapeutic drug monitoring may reduce toxicity of immunosuppression with similar efficacy.Methods/Design:An open-label, randomized, controlled, parallel-group, multicenter trial in lung transplant recipients will be conducted to investigate the safety and efficacy of immunosuppression guided by TTV monitoring as add-on to conventional therapeutic drug monitoring. Adult lung transplant recipients 21 - 42 days after transplantation are eligible to participate. Patients (N = 144) will be randomized 1:1 to the experimental intervention (Arm 1: Immunosuppression guided by TTV monitoring in addition to conventional therapeutic drug monitoring of tacrolimus trough levels) and control intervention (Arm 2: conventional therapeutic drug monitoring). Outcomes will be assessed 12 months after randomization with the change in glomerular filtration rate as the primary endpoint. Secondary endpoints will be additional measurements on renal function, allograft function, incidence of acute rejections, incidence of chronic lung allograft dysfunction, graft loss and infections.Discussion:The results of this randomized controlled trial may reduce toxicity of immunosuppression after lung transplantation while maintaining efficacy of immunosuppression. Study results are transferable to all other solid organ transplantations.Trial registration: ClinicalTrials.gov, NCT04198506. Registered 12 December 2019, https://www.clinicaltrials.gov/show/NCT04198506

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Postoperative Management of Lung Transplant Recipients in the Intensive Care Unit

Anesthesiology ◽

10.1097/aln.0000000000004054 ◽

2021 ◽

Author(s):

Matteo Di Nardo ◽

Jussi Tikkanen ◽

Shahid Husain ◽

Lianne G. Singer ◽

Marcelo Cypel ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Lung Transplantation ◽

Lung Transplant ◽

Postoperative Management ◽

Transplant Recipients ◽

Complex Interplay ◽

Hemodynamic Management ◽

Lung Transplant Recipients ◽

Evidence Based Guidelines

The number of lung transplantations is progressively increasing worldwide, providing new challenges to interprofessional teams and the intensive care units. The outcome of lung transplantation recipients is critically affected by a complex interplay of particular pathophysiologic conditions and risk factors, knowledge of which is fundamental to appropriately manage these patients during the early postoperative course. As high-grade evidence-based guidelines are not available, the authors aimed to provide an updated review of the postoperative management of lung transplantation recipients in the intensive care unit, which addresses six main areas: (1) management of mechanical ventilation, (2) fluid and hemodynamic management, (3) immunosuppressive therapies, (4) prevention and management of neurologic complications, (5) antimicrobial therapy, and (6) management of nutritional support and abdominal complications. The integrated care provided by a dedicated multidisciplinary team is key to optimize the complex postoperative management of lung transplantation recipients in the intensive care unit.

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Isavuconazole Is as Effective as and Better Tolerated Than Voriconazole for Antifungal Prophylaxis in Lung Transplant Recipients

Clinical Infectious Diseases ◽

10.1093/cid/ciaa652 ◽

2020 ◽

Cited By ~ 4

Author(s):

Palash Samanta ◽

Cornelius J Clancy ◽

Rachel V Marini ◽

Ryan M Rivosecchi ◽

Erin K McCreary ◽

...

Keyword(s):

Risk Factors ◽

Lung Transplantation ◽

Lung Transplant ◽

Fungal Infections ◽

Oral Intake ◽

Antifungal Prophylaxis ◽

Red Blood Cell Transfusion ◽

Transplant Recipients ◽

Independent Risk Factors ◽

Lung Transplant Recipients

Abstract Background Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. Methods A single-center, retrospective study of patients who received isavuconazole (September 2015–February 2018) or voriconazole (September 2013–September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. Results Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P = .02). IFIs were associated with increased mortality (P = .0001) and longer hospitalizations (P = .0005). Conclusions Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation.

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Early protein expression profile in bronchoalveolar lavage fluid and clinical outcomes in primary graft dysfunction after lung transplantation

European Journal of Cardio-Thoracic Surgery ◽

10.1093/ejcts/ezaa043 ◽

2020 ◽

Vol 58 (2) ◽

pp. 379-388

Author(s):

Anna E Frick ◽

Stijn E Verleden ◽

Sofie Ordies ◽

Annelore Sacreas ◽

Robin Vos ◽

...

Keyword(s):

Bronchoalveolar Lavage ◽

Lung Transplantation ◽

Lung Transplant ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Enzyme Linked Immunosorbent Assay ◽

Transplant Recipients ◽

Primary Graft Dysfunction ◽

Graft Dysfunction ◽

Lung Transplant Recipients

Abstract OBJECTIVES Primary graft dysfunction (PGD) remains a major post-transplant complication and is associated with increased morbidity and mortality. Mechanisms evoking PGD are not completely clear, but inflammation plays a central role. We investigated the association between PGD and inflammatory proteins present in immediate postoperative bronchoalveolar lavage. METHODS All double-lung recipients transplanted at our institution from 2002 to 2018 were included in our study. We retrospectively selected 80 consecutive lung transplant recipients with different PGD grades (n = 20 for each PGD grades 0–1 to 2–3). In bronchoalveolar lavage performed within the first 24 h after donor aortic cross-clamping following lung transplantation, concentrations of 30 cytokines, chemokines and growth factors were assessed by enzyme-linked immunosorbent assay (ELISA) and correlated with donor and recipient demographics and outcomes. For analysis, 2 groups were defined: ‘mild’ PGD (grade 0–1) and ‘severe’ PGD (grades 2–3). RESULTS Significant differences between mild and severe PGD were found in 8 biomarkers [interleukin (IL)-6, IL-10, IL-13, eotaxin, granulocyte colony-stimulating factor, interferon γ, macrophage inflammatory protein 1α, surfactant protein D (SP-D); P < 0.05]. Increased IL-10 and IL-13, but none of the other proteins, were associated with short-term outcome (longer time to extubation; P = 0.005 and P < 0.0001; increased intensive care unit stay; P = 0.012 and P < 0.0001; and hospital stay; P = 0.041 and P = 0.002). There were no significant differences in donor and recipient characteristics between the groups. CONCLUSIONS Expression profiles of key inflammatory mediators in bronchoalveolar lavage fluid differed significantly between lung transplant recipients with severe versus mild PGD and correlated with clinical outcome variables. Further research should focus on the early mechanisms leading to PGD.

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Invasive Fungal Infection After Lung Transplantation: Epidemiology in the Setting of Antifungal Prophylaxis

Clinical Infectious Diseases ◽

10.1093/cid/ciz156 ◽

2019 ◽

Vol 70 (1) ◽

pp. 30-39 ◽

Cited By ~ 19

Author(s):

Arthur W Baker ◽

Eileen K Maziarz ◽

Christopher J Arnold ◽

Melissa D Johnson ◽

Adrienne D Workman ◽

...

Keyword(s):

Lung Transplantation ◽

Amphotericin B ◽

Prevalence Rate ◽

Lung Transplant ◽

Tertiary Care ◽

Antifungal Prophylaxis ◽

Transplant Recipients ◽

Lipid Complex ◽

Amphotericin B Lipid Complex ◽

Lung Transplant Recipients

Abstract Background Lung transplant recipients commonly develop invasive fungal infections (IFIs), but the most effective strategies to prevent IFIs following lung transplantation are not known. Methods We prospectively collected clinical data on all patients who underwent lung transplantation at a tertiary care academic hospital from January 2007–October 2014. Standard antifungal prophylaxis consisted of aerosolized amphotericin B lipid complex during the transplant hospitalization. For the first 180 days after transplant, we analyzed prevalence rates and timing of IFIs, risk factors for IFIs, and data from IFIs that broke through prophylaxis. Results In total, 156 of 815 lung transplant recipients developed IFIs (prevalence rate, 19.1 IFIs per 100 surgeries, 95% confidence interval [CI] 16.4–21.8%). The prevalence rate of invasive candidiasis (IC) was 11.4% (95% CI 9.2–13.6%), and the rate of non-Candida IFIs was 8.8% (95% CI 6.9–10.8%). First episodes of IC occurred a median of 31 days (interquartile range [IQR] 16–56 days) after transplant, while non-Candida IFIs occurred later, at a median of 86 days (IQR 40–121 days) after transplant. Of 169 IFI episodes, 121 (72%) occurred in the absence of recent antifungal prophylaxis; however, IC and non-Candida breakthrough IFIs were observed, most often representing failures of micafungin (n = 16) and aerosolized amphotericin B (n = 24) prophylaxis, respectively. Conclusions Lung transplant recipients at our hospital had high rates of IFIs, despite receiving prophylaxis with aerosolized amphotericin B lipid complex during the transplant hospitalization. These data suggest benefit in providing systemic antifungal prophylaxis targeting Candida for up to 90 days after transplant and extending mold-active prophylaxis for up to 180 days after surgery.

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Outcome of Extracorporeal Photopheresis as an Add-On Therapy for Antibody-Mediated Rejection in Lung Transplant Recipients

Transfusion Medicine and Hemotherapy ◽

10.1159/000508170 ◽

2020 ◽

Vol 47 (3) ◽

pp. 205-213

Author(s):

Alberto Benazzo ◽

Nina Worel ◽

Stefan Schwarz ◽

Ulrike Just ◽

Anna Nechay ◽

...

Keyword(s):

Lung Transplantation ◽

Lung Transplant ◽

De Novo ◽

Hla Class I ◽

Class Ii ◽

Class I ◽

Extracorporeal Photopheresis ◽

Transplant Recipients ◽

Antibody Mediated Rejection ◽

Lung Transplant Recipients

Introduction: The diagnosis and treatment of antibody-mediated rejection (AMR) after lung transplantation has recently gained recognition within the transplant community. Extracorporeal photopheresis (ECP), currently used to treat chronic lung allograft dysfunction, modulates various pathways of the immune system known to be involved in AMR. We hypothesize that adding ECP to established AMR treatments could prevent the rebound of donor-specific antibodies (DSA). Objectives: This study aimed to analyze the role of ECP as an add-on therapy to prevent the rebound of DSA. Methods: Lung transplant recipients who received ECP as an add-on therapy for pulmonary AMR between January 2010 and January 2019 were included in this single-center retrospective analysis. Baseline demographics of the patients, as well as their immunological characteristics and long-term transplant outcomes, were analyzed. Results: A total of 41 patients developed clinical AMR during the study period. Sixteen patients received ECP as an add-on therapy after first-line AMR treatment. Among the 16 patients, 2 (13%) had pretransplant DSA, both against human leukocyte antigen (HLA) class I (B38, B13, and C06). Fifteen patients (94%) developed de novo DSA (dnDSA), i.e., 10 (63%) against class I and 14 (88%) against class II. The median time to dnDSA after lung transplantation was 361 days (range 25–2,548). According to the most recent International Society of Heart and Lung Transplantation (ISHLT) consensus report, 2 (13%) patients had definite clinical AMR, 6 (38%) had probable AMR, and 7 (44%) had possible AMR. The median mean fluorescence intensity (MFI) of dnDSA at the time of clinical diagnosis was 4,220 (range 1,319–10,552) for anti-HLA class I and 10,953 (range 1,969–27,501) for anti-HLA class II antibodies. ECP was performed for a median of 14 cycles (range 1–64). MFI values of dnDSA against HLA classes I and II were significantly reduced over the treatment period (for anti-class I: 752; range 70–2,066; for anti-class II: 5,612; range 1,689–21,858). The 1-year survival rate was 55%. No adverse events related to ECP were reported in any of the patients. Conclusions: ECP is associated with a reduction of dnDSA in lung transplant recipients affected by AMR. Prospective studies are warranted to confirm the beneficial effects of ECP in the setting of AMR.

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