Search

Aims Current non-invasive screening methods for cardiac allograft rejection have shown limited discrimination and are yet to be broadly integrated into heart transplant care. Given electrocardiogram (ECG) changes have been reported with severe cardiac allograft rejection, this study aimed to develop a deep-learning model, a form of artificial intelligence, to detect allograft rejection using the 12-lead ECG (AI-ECG). Methods and results Heart transplant recipients were identified across three Mayo Clinic sites between 1998 and 2021. Twelve-lead digital ECG data and endomyocardial biopsy results were extracted from medical records. Allograft rejection was defined as moderate or severe acute cellular rejection (ACR) based on International Society for Heart and Lung Transplantation guidelines. The extracted data (7590 unique ECG-biopsy pairs, belonging to 1427 patients) was partitioned into training (80%), validation (10%), and test sets (10%) such that each patient was included in only one partition. Model performance metrics were based on the test set (n = 140 patients; 758 ECG-biopsy pairs). The AI-ECG detected ACR with an area under the receiver operating curve (AUC) of 0.84 [95% confidence interval (CI): 0.78–0.90] and 95% (19/20; 95% CI: 75–100%) sensitivity. A prospective proof-of-concept screening study (n = 56; 97 ECG-biopsy pairs) showed the AI-ECG detected ACR with AUC = 0.78 (95% CI: 0.61–0.96) and 100% (2/2; 95% CI: 16–100%) sensitivity. Conclusion An AI-ECG model is effective for detection of moderate-to-severe ACR in heart transplant recipients. Our findings could improve transplant care by providing a rapid, non-invasive, and potentially remote screening option for cardiac allograft function.

Background We have previously shown bone marrow-derived mesenchymal stem cells (MSCs) may shift immune responses toward anti-inflammatory pathways and stabilize the course of obstructive chronic lung allograft syndrome (o-CLAD) after lung transplantation. In this study, we measured the response of lower dose infusions. Methods We infused low-dose MSCs intravenously in 13 patients who had developed moderate-to-severe o-CLAD. Three had previously received an infusion of MSCs from a different donor and were re-dosed at 1 × 106 MSC/kg, while 5 received a first dose at 1 × 106 MSC/kg and five received an even lower dose at 0.5 × 106 MSC/kg. We recorded pulmonary function tests before and after infusion, and patients were followed clinically for 12 months. Results Infusions were well tolerated, and no significant adverse events were recorded in the first 30 days. There was significant decline (mean ± SD) in forced vital capacity (FVC) (3.49 ± 1.03 vs 3.18 ± 0.94 L, P = .03) and forced expiratory volume in 1 second (FEV1) (2.28 ± 0.86 vs 1.77 ± 0.49 L, P = .04) over the year preceding infusion. FVC (3.18 ± 0.94 vs 3.46 ± 0.99 L, P = .53) and FEV1 was not significantly changed (1.77 ± 0.49 vs 1.88 ± 0.75, P = .72) when comparing values immediately prior to infusion to those obtained 1 year after infusion, indicating a possible stabilizing effect on lung function decline due to o-CLAD. Conclusion Intravenous infusions of bone marrow-derived MSCs are well tolerated in lung transplant recipients with moderate-to-severe CLAD. Low-dose MSCs appear to slow progression of CLAD in some patients.

Guillain-Barré syndrome (GBS) is an immune-mediated polyneuropathy, which is characterized by areflexia and ascending paresthesia which can progress to a respiratory failure. Certain conditions, such as vasculitis and heavy metal and drug toxicity, may have misleadingly similar clinical presentation to GBS. We describe a case of a patient with cystic fibrosis and intravenous colistin-induced neurotoxicity mimicking GBS. The patient had used inhaled colistin on five occasions with no adverse effects, however, developed symptoms on the second day of intravenous treatment. Overlapping findings between immune-mediated polyneuropathy and drug-induced neurotoxicity include limb paresthesia and decreased reflexes. Perioral tingling, however, is a common presentation of colistin-induced neurotoxicity, and therefore, is an important differentiating factor. Early diagnosis prevents further neurologic decline, extensive unnecessary workup and potentially harmful incorrect management.

Purpose Induction immunosuppression has improved the long‐term outcomes after lung transplant. This is the first report exploring the association of induction immunosuppression with the development of de novo donor‐specific human leukocyte antigen (HLA) antibodies (DSA) in lung transplant recipients (LTR). Methods Sixty‐seven consecutive primary LTR were followed for 3 years posttransplant. A total of 41/67 (61%) LTR‐received induction immunosuppression using a single dose of rabbit Antithymocyte Globulin (rATG; 1.5 mg/kg) within 24 h of transplant. All recipients had a negative flow cytometry crossmatch on the day of transplant. Serum samples at 1, 3, 6, and 12 months posttransplant were assessed for the presence of de novo HLA DSA. Results De novo HLA DSA were detected in 22/67 (32.8%) LTR within 1‐year posttransplant. Of these, 9/41 (21.9%) occurred in the induction therapy group and 13/26 (50%) in the noninduction group. Class II DSA were detected in 3/41 (7.3%) LTR who received induction compared to 9/26 (34.6%) LTR without induction immunosuppression (p = .005). Differences in overall survival or freedom from chronic lung allograft dysfunction rates between the two groups were not statistically significant. Conclusion Induction immunosuppression utilizing a modified regimen of single‐dose rATG is associated with a significant reduction in de novo DSA production in LTR., Induction immunosuppression utilizing a modified single‐dose antithymocyte globulin is associated with a significant reduction in de novo DSA production post lung transplant

Recent years have witnessed evolution of lung allocation strategies to prioritize sicker recipients. In the pre-transplant period, this has translated into increased utilization of invasive extracorporeal or mechanical ventilatory support as a bridge to lung transplantation. The morbidity associated with these strategies warrants consideration to less invasive respiratory support modalities. Herein, we present a case highlighting successful bridge to lung transplantation with a relatively non-invasive negative pressure ventilator.

Declining a donor when there is a reasonable possibility that the abnormality on chest imaging could be benign carries the risk of losing out on potentially usable lungs in an already parched landscape of donor organ availability. Cautiously aggressive attitudes to acceptance of borderline donors can help bridge the significant discrepancy that exists between the demand and availability of donor organs. Herein, we present a case highlighting successful bilateral lung transplantation from a relatively imperfect donor.

A key component of the perioperative management of lung transplant recipients is the avoidance of airway and pulmonary complications in the immediate postoperative period. The AnapnoGuard™ AG100s (Hospitech Respiration Ltd, Kfar Saba, Israel), a novel endotracheal tube and ventilation management system, holds the potential to assist the care team in attenuating complications related to excessive cuff pressure, subglottic secretions, and endobronchial intubation. In this report, we describe the successful use of the AnapnoGuard™ AG100s system in the postoperative management of a lung transplant recipient.

Background: Coronavirus disease 2019 (COVID-19) is a global pandemic, which is associated with venous thromboembolism and pulmonary embolism (PE). This study aimed to estimate the pooled incidence of PE among patients hospitalized with COVID-19 within the published literature. Methods: This systematic review and meta-analysis was performed according to PRISMA guidelines. An electronic search using MEDLINE /PubMed, ScienceDirect, Cochrane, and OpenGray databases was conducted May 19th, 2020. Eligible studies included sufficient data to calculate the incidence of PE diagnosed during hospitalization in patients with COVID-19. Case reports were excluded. Quality was assessed using the Newcastle-Ottawa scale (observational cohort and case-control), AXIS tool (cross-sectional), and quality assessment tool (case series). Demographics and PE incidence data were extracted from the included studies and analyzed with R language. The pooled incidence of PE in patients hospitalized with COVID-19 was calculated. Results: The database search identified 128 records. Ten observational studies were eligible and were included in the meta-analysis with a total of 1722 patients (mean age= 63.36). .The incidence of PE was noted to be higher in males. The D-dimer levels were specified between PE group and non-PE group in only three studies, while the remaining either reported it improperly or had missing data.The pooled PE incidence in patients hospitalized with COVID-19 was 17% (95% CI: 0.1-0.26). There was a high degree of study heterogeneity (I2 = 94%, p Conclusion: The pooled PE incidence in patients hospitalized with COVID-19 is 17%. This increased incidence is greater than that previously reported in the general population of non-COVID-19. Attention and further investigation of this risk is warranted.

Purpose Aim of this study is to assess lung utilization from donors with high Body Mass Index (BMI) and outcomes of lung transplant recipients from these donors. Methods We reviewed United Network for Organ Sharing (UNOS) registry for first-time adult lung transplant recipients and donors from 06/2005 to 03/2017. Donors were stratified into 4 groups according to their BMI: normal 18.5-29.9, underweight 35 kg/m2. Percentage lung utilization for each group was compared using Chi square test. Recipient survival was estimated with Kaplan-Meier curves and compared using multivariate Cox regression model. Results Of 20380 donors, 15765 (77.3%) donors had normal BMI, 916 (4.5%) were underweight, 2406 (11.8%) were obese and 1262 (6%) were moderately/severely obese. No significant difference was seen among 4 groups in terms of lung transplant survival (adjusted p=0.59, multivariate cox regression model, Figure 1). The 1, 3 and 5 year recipient survival rates were: 85.8 %, 68.9% and 55.1% in normal donor BMI group, 85.4%, 68.8% and 57.1% in underweight donor group, 86.3%, 67.6% and 56.0 % in the obese donor group and 86.7%, 67.1%, and 54.2 %in moderately/severely obese donor group, respectively. When donors with normal BMI were used as reference, the hazard ratio (95% confidence interval) for donors with obesity was 0.97 (0.88-1.07), donors with moderate/severe obesity was 1.03 (0.96-1.10) and for underweight donors was 1.05 (0.95-1.17). The lung utilization from donors with normal BMI was 31.1% and from donors with BMI >30 was 17% (p Conclusion There is no significant difference in lung transplant recipient survival among the 4 donor BMI groups but there is lower organ utilization in the obese groups. Lungs from donors with high BMI should be considered more carefully before turning them down.

Purpose De novo donor-specific anti-HLA antibodies (DSA) have been associated with significantly increased risk for antibody-mediated rejection (AMR) and lung allograft dysfunction. Induction immunosuppression has improved the long-term outcome of lung transplantation. However, the impact of Induction immunosuppression on the development of de novo DSA in lung transplant recipients is not well defined Methods We assessed the relationship between using rabbit Antithymocyte Globulin (rATG) for induction immunosuppression and the development of de novo DSA in a cohort of consecutive lung transplant recipients (n = 67) that were followed for 12 months post-transplant. All recipients had negative flow cytometry crossmatch on the day of transplant. Anti-HLA antibodies in the serum were assessed at 1, 3, 6, 12 months post-transplant. DSA were defined as having a Mean Fluorescence Intensity (MFI) > 1000 Results 41/67 lung transplant recipients (LTR) received a single dose rATG (1.5 mg/kg) within 24 hours of transplant. De novo DSA were detected in 10/41 (24.3%) compared to 13/26 (50%) ATG and no ATG groups respectively at 12 months post-transplant. However, de novo DSA were detected within 1 month post-transplant in 5/10 (50%) compared to 3/13 (23.3%) rATG and no rATG groups respectively. There was no significant difference in the de novo DSA MFI levels between the rATG group (median MFI = 1379 & 2124 for class I & II respectively) compared to the no rATG group (median MFI = 2186 & 2388 for class I & II respectively) at 12 months post-transplant. De novo DSA prevalence is shown in Table 1. Conclusion Induction with a single dose of rATG is associated with a significant decrease in the prevalence of HLA de novo DSA in LTR at 12 months post-transplant. De novo DSA were detected earlier in the rATG group compared to no rATG group. These findings warrant investigating in a larger study the impact of rATG induction on de novo DSA levels and lung allograft dysfunction.

Purpose Tricuspid valve regurgitation (TR) is a frequent finding in patients undergoing lung transplantation (LTx). The prognostic significance and rate of regression of TR after LTx are under reported. Purpose of this study is to assess tricuspid valve regurgitation (TR) regression after lung transplantation (LTx) in patients with trivial to severe pre-operative TR. Methods We retrospectively reviewed and prospectively collected records of 553 patients who had LTx at our institution from 2001 to 2017. Pre and post-op echocardiograms were retrospectively reviewed and was graded for severity of TR, right ventricular (RV) enlargement, tricuspid annular plane systolic excursion (TAPSE), mean pulmonary arterial pressure (mPAP) and other hemodynamics. Continuous variables were summarized with median and range (min, max) while categorical variables with frequency and percent. All statistical analyses were performed with R Statistical Software (version 3.4.2; R Foundation for Statistical Computing, Vienna, Austria). Results The mean age of the patients was 64 (21.0, 82.0) years and 324 (58.7%) were males. Out of all patients, the majority 302 (55.8%) suffered from IPF, followed by 84 (15.3%) PH, 79 (14.3%) COPD, 65 (11.8%) emphysema, and 31 (5.6%) CF. 417 (75.4%) had double LTx and 136 (24.6%) of patients required single LTx . Pre-operative tricuspid valve regurgitation reported as trivial (N=265, 47.9%) mild (N=235, 42.5%), moderate (N=40, 7.3%) and severe (N=13, 2.3%). TR improved from pre to post operatively in 193 (34.9%) out of 553 patients (p Conclusion Moderate to severe TR significantly improved after lung transplant. Our findings suggest that preoperative TR in lung recipients is mostly functional and will resolve after LTx. There is no need for tricuspid valve repair at the time of transplantation.

Pulmonary hypertension (PHTN) can be seen in patients with connective tissue disease (CTD). The typical pathology associated with CTD is interstitial fibrosis and hypertensive pulmonary arteriopathy. We describe 4 patients with CTD and PHTN unexpectedly found to have pulmonary capillary hemangiomatosis (PCH) at explant after lung transplantation or autopsy. Pulmonary capillary hemangiomatosis is defined as a proliferation of capillaries in alveolar walls and can clinically cause PHTN. We detail the pathologic findings of PCH, describe the differential diagnosis, and present a review of the literature on the possible association of PCH with CTD. Although PCH may present clinically as PHTN, it is critical to differentiate between the typical CTD-associated interstitial fibrosis with hypertensive pulmonary arteriopathy and PCH because the treatment is different. We provide the largest case series to date and highlight the need for pathologists to have a high level of suspicion for PCH in patients with CTD.

Mixed connective tissue disease (MCTD) is an immune-mediated systemic disorder characterised by serum autoantibodies against U1-ribonucleoprotein and diverse multisystemic clinical manifestations. Approximately 50% of patients with MCTD develop a radiologic pattern of interstitial lung disease (ILD). Our single centre, cross-sectional study sought to identify clinical and serologic associations of ILD in patients with MCTD which may serve as predictors of lung disease and prognosis.Patients who met validated criteria for diagnosis of MCTD were included in the study, and were further differentiated into study and control groups based on presence or absence of ILD.Multivariate logistic regression showed an association of two clinical variables: dysphagia with an R2 value of 0.33 (p-value0.001) and Raynaud's phenomenon with R2 value of 0.28 (p-value0.001).An association of dysphagia with the development of ILD in our study is in harmony with the existing literature. There are primarily case reports, suggesting an association of Raynaud's phenomenon with development of ILD in patients with undifferentiated CTD. To our knowledge, this is the first study highlighting the association of Raynaud's phenomenon with development of ILD in patients with MCTD. The mechanistic aspects of the association between Raynaud's phenomenon and ILD remain unexplored. The association of easily elicited historical and clinical features of MCTD with subtle, but worrisome, pulmonary pathology carries the promise of sensitising the unsuspecting clinician about the entity of ILD in MCTD.

Churg-Strauss angiitis is a rare vasculitic disorder affecting small- and medium-sized blood vessels. It is clinically characterized by the presence of a wide spectrum of multisystem organ involvement, with allergic rhinitis, asthma and peripheral blood eosinophilia as the most typical manifestations. The authors describe 2 cases of Churg-Strauss angiitis from an urban community of southern Louisiana, exhibiting an atypical presentation with myocardial ischemia and cerebrovascular complications. Epidemiology, pathophysiology and clinical overview are presented. The therapeutic management is also discussed.

Technological advances in recent years have translated into the availability of newer modalities to establish the cause of peripheral pulmonary nodules (PPN). Even though the verdict is still out on the ideal diagnostic modality, there is no doubt that the bronchoscope is becoming a popular tool in the armamentarium of physicians who deal with PPN. This article focuses on newer bronchoscopic modalities being studied for the work-up of PPN. The authors also summarize the value of established diagnostic modalities to provide a balanced perspective.

The worldwide 2009-2010 pandemic of novel H1N1 influenza reminds us that influenza can still be a lethal disease. Acute lung injury and acute respiratory distress syndrome (ARDS) have been the most devastating complications of this pathogen. We present a case of a previously healthy 40-year-old obese man who succumbed to H1N1-associated ARDS. In this focused review, we discuss the pathophysiologic peculiarities and management of acute lung injury/ARDS related to H1N1 infection.

DIPNECH is a rare and under-recognized disorder. Although it is still poorly understood, there has been a relative increase in recent publications surrounding this entity. Significance of DIPNECH can be gauged from the fact that the World Health Organization now recognizes it as one of the pre-invasive conditions for the development of carcinoid tumors in the lung. In this chapter, we summarize the key features of this enigmatic illness.

Ghrelin, a recently described peptide, has attracted significant attention in recent years, primarily in the context of its endocrine- and appetite-regulating effects. The versatility of this peptide is manifested in a rapidly expanding body of literature highlighting its nonendocrine functions. This review summarizes the available data on the immunomodulatory as well as the non–immune-mediated effects of ghrelin that form the scientific basis of its role in critical illness.

Adult onset Still's disease is an inflammatory disorder with a wide clinical presentation ranging from arthralgia and arthritis to rash and high-grade fever. Etiology of this rare disorder remains a mystery. We present two cases at the extreme ends of clinical presentation diagnosed with AOSD along with literature review for the same. Case one was self limiting, requiring only NSAIDS as treatment. The other was an unusual central nervous system manifestation of repeated seizures that were only responsive to pulse dose of methylprednisolone. Both met Yamaguchi criteria for adult onset Still's disease.

Foreign body aspiration is the fourth leading cause of death due to unintentional injuries. In 2004, 4470 people died because of inhalation or ingestion of food and other objects as per the National Safety Council Report. We report a rare case of accidental aspiration of an intact bag of cocaine, presenting with acute central airway obstruction and cardiopulmonary arrest, highlighting the challenges in the diagnosis and management strategies for this entity.

The worldwide 2009–2010 pandemic of novel H1N1 influenza reminds us that influenza can still be a lethal disease. Acute lung injury and acute respiratory distress syndrome (ARDS) have been the most devastating complications of this pathogen. We present a case of a previously healthy 40-year-old obese man who succumbed to H1N1-associated ARDS. In this focused review, we discuss the pathophysiologic peculiarities and management of acute lung injury/ARDS related to H1N1 infection.