Outcomes Following Lung Transplant for COVID-19-Related Complications in the US.

Importance: The COVID-19 pandemic led to the use of lung transplant as a lifesaving therapy for patients with irreversible lung injury. Limited information is currently available regarding the outcomes associated with this treatment modality. Objective: To describe the outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Design, Setting, and Participants: In this cohort study, lung transplant recipient and donor characteristics and outcomes following lung transplant for COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis were extracted from the US United Network for Organ Sharing database from March 2020 to August 2022 with a median (IQR) follow-up period of 186 (64-359) days in the acute respiratory distress syndrome group and 181 (40-350) days in the pulmonary fibrosis group. Overall survival was calculated using the Kaplan-Meier method. Cox proportional regression models were used to examine the association of certain variables with overall survival. Exposures: Lung transplant following COVID-19-related acute respiratory distress syndrome or pulmonary fibrosis. Main Outcomes and Measures: Overall survival and graft failure rates. Results: Among 385 included patients undergoing lung transplant, 195 had COVID-19-related acute respiratory distress syndrome (142 male [72.8%]; median [IQR] age, 46 [38-54] years; median [IQR] allocation score, 88.3 [80.5-91.1]) and 190 had COVID-19-related pulmonary fibrosis (150 male [78.9%]; median [IQR] age, 54 [45-62]; median [IQR] allocation score, 78.5 [47.7-88.3]). There were 16 instances of acute rejection (8.7%) in the acute respiratory distress syndrome group and 15 (8.6%) in the pulmonary fibrosis group. The 1-, 6-, and 12- month overall survival rates were 0.99 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.91-0.98), and 0.88 (95% CI, 0.80-0.94) for the acute respiratory distress syndrome cohort and 0.96 (95% CI, 0.92-0.98), 0.92 (95% CI, 0.86-0.96), and 0.84 (95% CI, 0.74-0.90) for the pulmonary fibrosis cohort. Freedom from graft failure rates were 0.98 (95% CI, 0.96-0.99), 0.95 (95% CI, 0.90-0.97), and 0.88 (95% CI, 0.79-0.93) in the 1-, 6-, and 12-month follow-up periods in the acute respiratory distress cohort and 0.96 (95% CI, 0.92-0.98), 0.93 (95% CI, 0.87-0.96), and 0.85 (95% CI, 0.74-0.91) in the pulmonary fibrosis cohort, respectively. Receiving a graft from a donor with a heavy and prolonged history of smoking was associated with worse overall survival in the acute respiratory distress syndrome cohort, whereas the characteristics associated with worse overall survival in the pulmonary fibrosis cohort included female recipient, male donor, and high recipient body mass index. Conclusions and Relevance: In this study, outcomes following lung transplant were similar in patients with irreversible respiratory failure due to COVID-19 and those with other pretransplant etiologies.

Lung Transplantation for Acute Respiratory Distress Syndrome.

In this review, we discuss the outcomes of patients with severe acute respiratory distress syndrome (ARDS). We discuss evidence that suggests that a significant proportion of patients with ARDS develop end-stage lung disease and die of pulmonary complications. In carefully selected patients with permanent lung damage, lung transplant can be a life-saving treatment.

Lung transplantation during the outbreak of Coronavirus Disease 2019 in China.

OBJECTIVES: The study objectives were to illustrate our workflow for lung donation and transplantation during the Coronavirus Disease 2019 crisis and to report our preliminary experience with perioperative care. METHODS: We retrospectively analyzed data in the China Lung Transplantation Registration from January 23, 2020, to March 23, 2020 (2020 cohort), compared with the same period in 2019 (2019 cohort). Pre- and post-lung transplantation management strategies, including measures aiming to prevent severe acute respiratory syndrome coronavirus 2 infection, were applied to all recipients, including 5 post-Coronavirus Disease 2019 transplants during the Coronavirus Disease 2019 pandemic period in China. RESULTS: Twenty-eight lung transplant procedures were performed, including lung transplant for 5 patients with acute respiratory distress syndrome due to Coronavirus Disease 2019-related pulmonary fibrosis. Compared with the 2019 cohort, more patients with urgent conditions received transplantation in 2020, with a shorter pre-lung transplant admission time and early mobilization post-lung transplant. A large proportion (60%) of lung donations were transported on high-speed trains and commercial flights or highways and commercial flights. Grafts in the preservation containers were handed over to the receiving staff at the airport for 40% (10/25) of donations, which reduced the unnecessary quarantine of transporting staff entering the city. Listed candidates were urgently transferred to other qualified centers in 17.9% of cases (5/28), which reduced the risk of severe acute respiratory syndrome coronavirus 2 exposure in Coronavirus Disease 2019-designated hospitals. The 90-day survival of the transplant recipients in 2020 was 85.7%, including 3 of 5 recipients (60%) who had critically severe Coronavirus Disease 2019. CONCLUSIONS: Lung transplant and donation amid Coronavirus Disease 2019 can be performed safely with coordinated efforts on medical resource sharing and medical staff protection based on stratification of the infection risk. Outcomes were not compromised during the Coronavirus Disease 2019 outbreak. Lung transplantion can be regarded as salvage therapy for critical patients with Coronavirus Disease 2019 with a confirmed positive turned negative virology status.

Emergency Lung Transplantation after COVID-19: Immunopathological Insights on Two Affected Patients.

We herein characterize the immunopathological features of two Italian COVID-19 patients who underwent bilateral lung transplantation (bLTx). Removed lungs underwent histopathological evaluation. Gene expression profiling (GEP) for immune-related signatures was performed on lung specimens and SARS-CoV-2-stimulated peripheral blood mononuclear cells (PBMCs). Cytokine levels were measured on lungs, bronchoalveolar lavage fluids and in culture supernatants. Pathological assessment showed extensive lung damage with the pattern of proliferative to fibrotic phases, with diffuse alveolar damage mimicking usual interstitial pneumonia (UIP). Lungs' GEP revealed overexpression of pathogen recognition receptors, effector cytokines and chemokines, immune activation receptors and of the inflammasome components. Multiplex cytokine analysis confirmed a proinflammatory state, with high levels of monocyte/macrophage chemotactic and activating factors and of IL-6 and TNF-α. A similar profile was observed in SARS-CoV-2-stimulated PBMCs collected 7 days after transplant. The pattern of tissue damage observed in the lungs suggests that this may represent the output of protracted disease, resembling a diffuse UIP-like picture. The molecular immune profiling supports the paradigm of a persistent proinflammatory state and sustained humoral immunity, conditions that are maintained despite the iatrogenic immunosuppression.

Stem cell therapy in coronavirus disease 2019: current evidence and future potential.

The end of 2019 saw the beginning of the coronavirus disease 2019 (COVID-19) pandemic that soared in 2020, affecting 215 countries worldwide, with no signs of abating. In an effort to contain the spread of the disease and treat the infected, researchers are racing against several odds to find an effective solution. The unavailability of timely and affordable or definitive treatment has caused significant morbidity and mortality. Acute respiratory distress syndrome (ARDS) caused by an unregulated host inflammatory response toward the viral infection, followed by multi-organ dysfunction or failure, is one of the primary causes of death in severe cases of COVID-19 infection. Currently, empirical management of respiratory and hematological manifestations along with anti-viral agents is being used to treat the infection. The quest is on for both a vaccine and a more definitive management protocol to curtail the spread. Researchers and clinicians are also exploring the possibility of using cell therapy for severe cases of COVID-19 with ARDS. Mesenchymal stromal cells are known to have immunomodulatory properties and have previously been used to treat viral infections. This review explores the potential of mesenchymal stromal cells as cell therapy for ARDS.

The potential role of trans-resveratrol/carboxymethylated (1.3/1.6)-ß-d-glucan minimizing symptoms and improve healing after functional endoscopic sinus surgery.

OBJECTIVE: This study aims to evaluate the effect of trans-resveratrol/carboxymethylated (1.3/1.6)-ß-d-glucan administered via nasal, after FESS, assessing nasal respiratory distress and nasal mucosa healing. PATIENTS AND METHODS: We enrolled 70 patients, from March 2019 to February 2020, with chronic nasal obstruction not responding to medical therapy and candidates to endoscopic nasal surgery. Patients were divided in two non-randomized groups: group A treated with trans-resveratrol/carboxymethylated (1.3/1.6)-ß-d-glucan administered via nasal, and group B treated with 0.9% nasal irrigation saline. Patients were clinically evaluated, in post-operative period, at 7 (T0), 15 (T1), and 30 days (T2) with fibroendoscopy. The CRS (chronic rhinosinusitis) questionnaire (Snot 20) was administrated at T0, T1, and T2. The findings were scored with respect to middle turbinate edema. In both Groups, the inferior turbinate's medial aspect was scraped using a sterile disposable Rhino-probe mucosal curette (Arlington Scientific, Inc., Springville, UT, USA) at T0, T1, and T2. RESULTS: Group A showed an improvement in Snot 20 in T1 and T2 both. The reduction of the mucosal edema and nasal secretion has been statistically significant in the Group A. A slight cell reduction was observed at T2 with respect to T1. This decreased pattern is more evident in nasal scraping from Group A. The appearance of epithelial cells at T2 of Group A is consistent with the reduction of inflammatory cells. CONCLUSIONS: We can assert that in Group A it appears less evident the presence of edema, nasal congestion and crusts, resulting in a quick recover.

Tension Pneumocephalus from Positive Pressure Ventilation Following Endoscopic Skull Base Surgery: Case Series and an Institutional Protocol for the Management of Postoperative Respiratory Distress.

BACKGROUND: Tension pneumocephalus (TP) is a rare but feared complication of endoscopic endonasal skull base surgery. In contrast to simple pneumocephalus, which is common after endoscopic transnasal approaches and managed conservatively, TP represents a neurosurgical emergency and mandates urgent decompression. CASE DESCRIPTION: Here we present 2 cases of TP as a consequence of positive pressure ventilation following endoscopic endonasal skull base surgery. Both occurred during resuscitation for postoperative hypoxia. These cases prompted the development of an institution-wide protocol to identify and manage patients at risk of TP after extended skull base approaches. CONCLUSIONS: To our knowledge, these are the only such cases of postoperative TP following positive pressure ventilation in the literature.

Laryngeal stent for acute and chronic respiratory distress in seven dogs with laryngeal paralysis.

Background: Laryngeal paralysis, failure of arytenoid cartilage, and vocal fold abduction are commonly seen in older medium to large breed dogs. Observation of laryngeal function in dogs and cats is performed by transoral visualization. There are a variety of surgical techniques; aspiration pneumonia is the most common complication associated with surgical correction of laryngeal paralysis. The aim of this case series is to report on the placement of a laryngeal silicone stent in seven dogs with laryngeal paralysis and its use as an alternative treatment of respiratory distress caused by laryngeal paralysis and/or its use for laryngeal stenosis as complication of laryngeal paralysis surgery. Case description: Seven dogs presented with either episode of gagging, mild-to-severe inspiratory distress, or cyanosis because of a laryngeal paralysis or laryngeal stenosis. In each case, the laryngeal paralysis was diagnosed by direct laryngoscopy. They were treated with a silicone laryngeal stent (Stening®) that substantially improved the clinical signs. Each dog had a different outcome because of other pathologies; however, the laryngeal pathology was successfully treated with the stent. Conclusion: The placement of the laryngeal stent is an easy technique to learn and practice, it could avoid the life-threatening complications of the laryngeal paralysis at the acute phase, and it could be a noninvasive and long-term alternative therapy for laryngeal paralysis in dogs. The results in these clinical cases are encouraging for considering the laryngeal stent as a therapeutic alternative.

Higher incidence of acute respiratory distress syndrome in cardiac surgical patients with elevated serum procalcitonin concentration: a prospective cohort study.

BACKGROUND: Inflammatory response is activated during cardiopulmonary bypass (CPB), which may lead to acute respiratory distress syndrome (ARDS) and procalcitonin (PCT) increases during this inflammatory response. The objective of the study was to validate whether patients with higher serum PCT concentrations have a higher incidence of ARDS. METHODS: The study was a prospective, single-center, observational cohort study. All patients who received cardiac surgery with CPB were screened for study eligibility. Patients were assigned to the PCT-elevated cohort or the control cohort according to serum PCT concentration on the first postoperative day with a cut-off value of 7.0 ng/mL. Patients were followed up until the 7th postoperative day. The primary endpoint was the incidence of ARDS, which was diagnosed according to the Berlin definition. RESULTS: A total of 296 patients were enrolled, 64 patients were assigned to the PCT-elevated cohort and 232 patients were assigned to the control cohort. PCT concentration was 16.23 ± 5.9 ng/mL in the PCT-elevated cohort, and 2.70 ± 1.43 ng/mL in the control cohort (p < 0.001). The incidence of ARDS was significantly higher in the PCT-elevated cohort than in the control cohort (21.9% versus 5.6%, p < 0.001). The incidence of moderate-to-severe ARDS was also significantly higher in the PCT-elevated cohort than in the control cohort (10.9% versus 0.4%, p < 0.001). The hazard ratio of ARDS at 7 days in the PCT-elevated cohort, as compared with the control cohort, was 6.8 (95% confidence interval 2.7 to 17.4). The hazard ratio of moderate-to-severe ARDS in the PCT-elevated cohort was 57.3 (95% confidence interval 10.4 to 316.3). The positive predictive value of PCT for ARDS and moderate-to-severe ARDS were 0.242 and 0.121, respectively; the negative predictive value of PCT for ARDS and moderate-to-severe ARDS were 0.952 and 1.0, respectively. CONCLUSION: Cardiac surgical patients with elevated PCT concentration have a higher incidence of ARDS. Elevated PCT may serve as a warning signal of postoperative ARDS in patients undergoing cardiac surgery with CPB. Study registration Chinese Clinical Trial Registry (ChiCTR-OCH-14005076).

Identification and Modulation of Microenvironment Is Crucial for Effective Mesenchymal Stromal Cell Therapy in Acute Lung Injury.

Rationale: There are controversial reports on applications of mesenchymal stromal cells (MSCs) in patients with acute respiratory distress syndrome (ARDS). Objectives: We hypothesized that lung microenvironment was the main determinant of beneficial versus detrimental effects of MSCs during ARDS. Methods: Lung proteome was profiled in three models of injury induced by acid instillation and/or mechanical ventilation in mice. Human gene of glutathione peroxidase-1 was delivered before MSC administration; or MSCs carrying human gene of IL-10 or hepatocyte growth factor were administered after lung injury. An inhibitory cocktail against IL-6, fibronectin, and oxidative stress was used in in vitro studies using human small airway epithelial cells and human MSCs after exposure to plasma of patients with ARDS. Measurements and Main Results: Distinct proteomic profiles were observed in three lung injury models. Administration of MSCs protected lung from ventilator-induced injury, whereas it worsened acid-primed lung injuries associated with fibrotic development in lung environment that had high levels of IL-6 and fibronectin along with low antioxidant capacity. Correction of microenvironment with glutathione peroxidase-1, or treatment with MSCs carrying human gene of IL-10 or hepatocyte growth factor after acid-primed injury, reversed the detrimental effects of native MSCs. Proteomic profiles obtained in the mouse models were also similarly observed in human ARDS. Treatment with the inhibitory cocktail in samples of patients with ARDS retained protective effects of MSCs in small airway epithelial cells. Conclusions: MSCs can be beneficial or detrimental depending on microenvironment at the time of administration. Identification of potential beneficiaries seems to be crucial to guide MSC therapy in ARDS.

Influencia de la caja torácica en el monitoreo de la mecánica respiratoria en síndrome de distrés respiratorio agudo / Chest wall effect on the monitoring of respiratory mechanics in acute respiratory distress syndrome

RESUMEN La mecánica del sistema respiratorio depende de las características del pulmón, la caja torácica y su interacción. En pacientes con síndrome de distrés respiratorio agudo bajo ventilación mecánica el monitoreo de la presión meseta en la vía aérea es fundamental debido a su valor pronóstico y su capacidad de reflejar el estrés pulmonar. Sin embargo, su validez puede verse afectada por cambios en las características mecánicas de la caja torácica, y además, no otorga información para la correcta titulación de presión positiva al final de la espiración en función de restablecer el volumen pulmonar. La influencia que la caja torácica ejerce sobre la mecánica del sistema respiratorio en síndrome de distrés respiratorio agudo no ha sido completamente descripta y es probable que haya sido sobredimensionada pudiendo conducir a toma de decisiones erróneas. Ante la insuflación con presión positiva al final de la espiración, la carga impuesta por la caja torácica es despreciable. En condiciones dinámicas, desplazar esta estructura demanda un cambio de presión cuya magnitud se relaciona con sus características mecánicas, dicha carga se mantiene constante independientemente del volumen a partir del cual es insuflada. Por lo que cambios en la presión en la vía aérea reflejan modificaciones en las condiciones mecánicas del pulmón. El monitoreo avanzado podría reservarse para pacientes con incremento de la presión intra-abdominal en los que no pueda implementarse una estrategia de ventilación mecánica protectora. Las estimaciones de reclutamiento alveolar basadas en la mecánica del sistema respiratorio podrían ser reflejo del diferente comportamiento de la caja torácica a la insuflación y no verdadero reclutamiento alveolar.

ABSTRACT The respiratory system mechanics depend on the characteristics of the lung and chest wall and their interaction. In patients with acute respiratory distress syndrome under mechanical ventilation, the monitoring of airway plateau pressure is fundamental given its prognostic value and its capacity to assess pulmonary stress. However, its validity can be affected by changes in mechanical characteristics of the chest wall, and it provides no data to correctly titrate positive end-expiratory pressure by restoring lung volume. The chest wall effect on respiratory mechanics in acute respiratory distress syndrome has not been completely described, and it has likely been overestimated, which may lead to erroneous decision making. The load imposed by the chest wall is negligible when the respiratory system is insufflated with positive end-expiratory pressure. Under dynamic conditions, moving this structure demands a pressure change whose magnitude is related to its mechanical characteristics, and this load remains constant regardless of the volume from which it is insufflated. Thus, changes in airway pressure reflect changes in the lung mechanical conditions. Advanced monitoring could be reserved for patients with increased intra-abdominal pressure in whom a protective mechanical ventilation strategy cannot be implemented. The estimates of alveolar recruitment based on respiratory system mechanics could reflect differences in chest wall response to insufflation and not actual alveolar recruitment.

Mesenchymal Stem Cells From Bone Marrow, Adipose Tissue, and Lung Tissue Differentially Mitigate Lung and Distal Organ Damage in Experimental Acute Respiratory Distress Syndrome.

OBJECTIVES: Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome. DESIGN: Animal study and primary cell culture. SETTING: Laboratory investigation. SUBJECTS: Seventy-five Wistar rats. INTERVENTIONS: Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium). MEASUREMENTS AND MAIN RESULTS: Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1ß, keratinocyte-derived chemokine, transforming growth factor-ß, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue. Additionally, mesenchymal stem cells differently modulated the secretion of biomarkers by macrophages depending on their source. CONCLUSIONS: Mesenchymal stem cells from different sources led to variable responses in lungs and distal organs. Bone marrow and adipose tissue mesenchymal stem cells yielded greater beneficial effects than lung tissue mesenchymal stem cells. These findings may be regarded as promising in clinical trials.

Transthoracic Littre's hernia presenting with faecopneumothorax following perforation of the Meckel's diverticulum: a late complication of oesophagectomy.

A Littre's hernia is an unusual phenomenon where a Meckel's diverticulum protrudes through a potential abdominal opening. We wish to present a unique case of a 79-year-old man with respiratory distress following a fall from standing, initially managed as a haemothorax. After a chest drain was placed, bowel contents were drained from the pleural cavity and he was taken to theatre. He had a history of minimally invasive oesophagectomy for cancer and had subsequently developed a diaphragmatic hernia. A blind ending diverticulum with a perforation at its tip was found in the left oblique lung fissure that was subsequently confirmed histologically as a perforated Meckel's diverticulum. The patient had a prolonged stay on the intensive care unit with a left-sided empyema that was managed radiologically prior to discharge. Unfortunately 4 months postoperatively, he passed away from hospital-acquired pneumonia on a rehabilitation ward.

Presentation and Management of Giant Fibrovascular Polyps of the Hypopharynx and Esophagus.

OBJECTIVE: Fibrovascular polyps of the hypopharynx and esophagus are rare, with few case reports in the literature. In this article, we present our institutional experience with a focus on airway and surgical management. STUDY DESIGN: Case series. SETTING: Tertiary academic institution. METHODS: A retrospective review was conducted of 4 patients that presented to a tertiary medical center with fibrovascular polyps between 1990 and 2012. Patient demographics, clinical presentation, diagnostic studies, and surgical approaches were reviewed. A review of the published literature was also performed. RESULTS: The average age at presentation was 72 years (range, 59-85 years). Among the 4 patients, 2 presented with airway compromise requiring tracheotomy. All patients had removal of the polyp shortly after presentation; 2 underwent transcervical approaches with lateral pharyngotomy/esophagotomy, and the other 2 had endoscopic removal. The polyps arose from the hypopharynx in 3 patients and upper esophagus in 1. Three patients had complete resolution of their symptoms and remained disease free. One patient had recurrence of the polyp 2 years later and is currently being observed. CONCLUSION: Fibrovascular polyps are rare tumors of the hypopharynx/esophagus that present in older adults. Although benign, they can cause life-threatening airway compromise that may necessitate tracheotomy. We present 4 cases of fibrovascular polyps and discuss our evolving surgical management, including endoscopic removal.

Acute respiratory distress syndrome: does histology matter?

Kao et al. have reported in Critical Care the histological findings of 101 patients with acute respiratory distress syndrome (ARDS) undergoing open lung biopsy. Diffuse alveolar damage (DAD), the histological hallmark of ARDS, was present in only 56.4% of cases. The presence of DAD was associated with higher mortality. Evidence from this and other studies indicates that the clinical criteria for the diagnosis of ARDS identify DAD in only about half of the cases. On the contrary, there is evidence that the clinical course and outcome of ARDS differs in patients with DAD and in patients without DAD. The discovery of biomarkers for the physiological (increased alveolocapillary permeability) or histological (DAD) hallmarks of ARDS is thus of paramount importance.