Context-dependent roles of mitochondrial LONP1 in orchestrating the balance between airway progenitor versus progeny cells.

While all eukaryotic cells are dependent on mitochondria for function, in a complex tissue, which cell type and which cell behavior are more sensitive to mitochondrial deficiency remain unpredictable. Here, we show that in the mouse airway, compromising mitochondrial function by inactivating mitochondrial protease gene Lonp1 led to reduced progenitor proliferation and differentiation during development, apoptosis of terminally differentiated ciliated cells and their replacement by basal progenitors and goblet cells during homeostasis, and failed airway progenitor migration into damaged alveoli following influenza infection. ATF4 and the integrated stress response (ISR) pathway are elevated and responsible for the airway phenotypes. Such context-dependent sensitivities are predicted by the selective expression of Bok, which is required for ISR activation. Reduced LONP1 expression is found in chronic obstructive pulmonary disease (COPD) airways with squamous metaplasia. These findings illustrate a cellular energy landscape whereby compromised mitochondrial function could favor the emergence of pathological cell types.

An Unexpected Cause of Lung Disease Identified After Lung Transplantation.

CASE PRESENTATION: A 54-year-old woman with systemic lupus erythematosus with associated interstitial lung disease (ILD) presented to the lung transplant clinic for assessment of candidacy for transplantation. She was initially diagnosed with ILD based on clinical and radiographic features (never underwent lung biopsy). In addition, she had associated mixed group I/III pulmonary arterial hypertension. The patient had no family history of pulmonary disease and had never used tobacco and did not have a history of illicit drug use. She was maintained on systemic immunosuppression with hydroxychloroquine, mycophenolate mofetil, and nintedanib for ILD as well as inhaled treprostinil, sildenafil, and macitentan for pulmonary arterial hypertension. Given her progressive symptoms on maximal medical therapy, she was referred for consideration to undergo lung transplantation.

Treatment of Bronchopleural and Alveolopleural Fistulas in Acute Respiratory Distress Syndrome With Extracorporeal Membrane Oxygenation, a Case Series and Literature Review.

OBJECTIVES: To describe a ventilator and extracorporeal membrane oxygenation management strategy for patients with acute respiratory distress syndrome complicated by bronchopleural and alveolopleural fistula with air leaks. DESIGN SETTING AND PARTICIPANTS: Case series from 2019 to 2020. Single tertiary referral center-University of California, San Diego. Four patients with various etiologies of acute respiratory distress syndrome, including influenza, methicillin-resistant Staphylococcus aureus pneumonia, e-cigarette or vaping product use-associated lung injury, and coronavirus disease 2019, complicated by bronchopleural and alveolopleural fistula and chest tubes with air leaks. MEASUREMENTS AND MAIN RESULTS: Bronchopleural and alveolopleural fistula closure and survival to discharge. All four patients were placed on extracorporeal membrane oxygenation with ventilator settings even lower than Extracorporeal Life Support Organization guideline recommended ultraprotective lung ventilation. The patients bronchopleural and alveolopleural fistulas closed during extracorporeal membrane oxygenation and minimal ventilatory support. All four patients survived to discharge. CONCLUSIONS: In patients with acute respiratory distress syndrome and bronchopleural and alveolopleural fistula with persistent air leaks, the use of extracorporeal membrane oxygenation to allow for even lower ventilator settings than ultraprotective lung ventilation is safe and feasible to mediate bronchopleural and alveolopleural fistula healing.

E-cigarette, or vaping, product use-associated lung injury (EVALI) treated with veno-venous extracorporeal membrane oxygenation (VV-ECMO) and ultra-protective ventilator settings.

A 19-year-old man vaping with tetrahydrocannabinol presented with dyspnoea and right pneumothorax. History, imaging and negative infectious workup were consistent with E-cigarette, or vaping, product use-associated lung injury (EVALI). Treated with systemic steroids, he developed acute respiratory distress syndrome and was intubated requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) by hospital day 3. Using VV-ECMO, very-low tidal volume ventilation of 1.5 cc/kg was achieved, as was daily ambulation. VV-ECMO was decannulated on hospital day 9 and the patient was extubated the next day. He was discharged home on hospital day 13 without oxygen. At post-intensive care unit clinic follow-up, he had lost 20 kg of weight while hospitalised and reported nightmares. Patients with EVALI may be supported with VV-ECMO, which allows ultra-lung-protective mechanical ventilation that may minimise ventilator-induced lung injury. Follow-up in patients with EVALI is essential to diagnose and treat comorbidities, follow lung function and prevent relapses.

Homologous and heterologous assessment of a novel biomaterial for venous patch.

OBJECTIVE: This study evaluated swine and bovine pulmonary visceral pleura (PVP) as a vascular patch. Venous patches are frequently used in surgery for repair or reconstruction of veins. Autologous patches are often limited by the number and dimension of donor tissue and can result in donor complications. Bovine pericardium is the most common heterologous patch used by vascular surgeons. Researchers, however, are continually seeking to improve heterologous and synthetic patches for improved outcome. METHODS: The PVP was peeled from swine and bovine lungs and cross-linked with glutaraldehyde. After sterilization and rinsing, the PVP patches were implanted in the jugular vein (10 × 35 mm) of pigs and dogs. Patency was evaluated by ultrasound, and animals were euthanized at 2 and 4 months. Neoendothelium and neomedia were evaluated by histologic analysis. RESULTS: The jugular vein patched by PVP in pigs and dogs remained patent at 2 and 4 months with no adhesions, inflammation, or aneurysm in the patches. The biomarkers of endothelial cells-factor VIII, platelet/endothelial cell adhesion molecule 1, and endothelial nitric oxide synthase-were detected in the neoendothelial cells. The expression of vascular smooth muscle cell (VSMC) α-actin was robust in the neomedia at 2 and 4 months. Neomedia composed of VSMCs developed to nearly double the thickness of adjacent jugular vein. The circumferential orientation of VSMCs in neomedia further increased in the 4-month group. CONCLUSIONS: The cross-linked swine and bovine PVP patch has a nonthrombogenic surface that maintains patency. The PVP patch may overcome the pitfall of compliance mismatch of synthetic patches. The proliferation of vascular cells assembled in the neoendothelium and neomedia in the patches may support long-term patency.

Novel Use of Cangrelor With Heparin During Cardiopulmonary Bypass in Patients With Heparin-Induced Thrombocytopenia Who Require Cardiovascular Surgery: A Case Series.

Optimal anticoagulation strategy during cardiopulmonary bypass (CPB) remains uncertain in patients with heparin-induced thrombocytopenia (HIT) who require urgent/emergent cardiac surgery. We describe our strategy and experience with utilizing cangrelor in combination with heparin for anticoagulation during CPB in patients with different phases of HIT undergoing a wide range of urgent/emergent cardiovascular surgery. Cangrelor is an intravenous direct-acting P2Y12 platelet receptor antagonist that achieves therapeutic effect and eliminates rapidly. Its antiplatelet activity is unaffected by stagnation of blood, nor is it influenced by patient's sex, age, renal status, or hepatic function. Our institutional alternative intraoperative anticoagulation strategy for HIT patients is to administer cangrelor with a loading dose of 30 µg/kg, followed by continuous infusion of 4 µg/kg/min throughout CPB via a dedicated intravenous access. VerifyNow P2Y12 reaction unit point-of-care assay is utilized to monitor platelet inhibition throughout surgery. Cangrelor infusion is discontinued 10 minutes prior to heparin reversal with protamine. Ten urgent/emergent cardiovascular surgeries were performed at our institution using cangrelor with heparin for anticoagulation during CPB, and the majority were pulmonary thromboendarterectomy (60%). HIT was confirmed in 3 cases and was suspected in 4 which was found to be negative after the operation. One case of subacute B HIT and 2 cases of remote HIT were included in this series. This novel alternative intraoperative anticoagulation strategy was well tolerated by all patients. There was neither serious postoperative thrombotic event nor major postoperative bleeding complication that required reoperation. One death occurred in a patient with advanced intracardiac malignancy, whose life support was ultimately withdrawn postoperatively. Median postoperative intensive care unit stay was 7.2 ± 5.5 days, while median postoperative hospital stay was 16.3 ± 10.8 days. In patients with various phases of HIT who require urgent/emergent on-pump cardiovascular surgery, the use of cangrelor with heparin may be a convenient, safe, and effective alternative intraoperative anticoagulation strategy providing acceptable outcomes.

Successful Use of Cangrelor and Heparin for Cardiopulmonary Bypass in a Patient With Heparin-Induced Thrombocytopenia and End-Stage Renal Disease: A Case Report.

Heparin is the only well-established anticoagulant medication for cardiopulmonary bypass making selecting an alternative anticoagulant challenging in patients with heparin-induced thrombocytopenia. Other anticoagulant medications can cause significant postoperative bleeding, especially in patients with end-stage renal disease. We present a case of a 63-year-old woman requiring aortic valve replacement with a history of heparin-induced thrombocytopenia and end-stage renal disease. Cangrelor and heparin were successfully used during cardiopulmonary bypass, offering an option for anticoagulation management for a uniquely challenging patient population.

Severity of Acute Kidney Injury in the Post-Lung Transplant Patient Is Associated With Higher Healthcare Resources and Cost.

OBJECTIVE: Perioperative risk factors and the clinical impact of acute kidney injury (AKI) and failure after lung transplantation are not well described. The incidences of AKI and acute renal failure (ARF), potential perioperative contributors to their development, and postdischarge healthcare needs were evaluated. DESIGN: Retrospective. SETTING: University hospital. PARTICIPANTS: Patients undergoing lung transplantation between January 1, 2011 and December 31, 2015. MEASURED DATA: The incidences of AKI and ARF, as defined using the Risk, Injury, Failure, Loss, End-Stage Renal Disease criteria, were measured. Perioperative events were analyzed to identify risk factors for renal compromise. A comparison of ventilator days, intensive care unit (ICU) and hospital lengths of stay (LOS), 1-year readmissions, and emergency department visits was performed among AKI, ARF, and uninjured patients. MEASUREMENTS AND MAIN RESULTS: Ninety-seven patients underwent lung transplantation; 22 patients developed AKI and 35 patients developed ARF. Patients with ARF had significantly longer ICU LOS (12 days v 4 days, p < 0.001); ventilator days (4.5 days v 1 day, p < 0.001); and hospital LOS (22.5 days v 14 days, p < 0.001) compared with uninjured patients. Patients with AKI also had significantly longer ICU and hospital LOS. Patients with ARF had significantly more emergency department visits and hospital readmissions (2 v 1 readmissions, p = 0.002) compared with uninjured patients. A univariable analysis suggested that prolonged surgical time, intraoperative vasopressor use, and cardiopulmonary bypass use were associated with the highest increased risk for AKI. Intraoperative vasopressor use and cardiopulmonary bypass mean arterial pressure <60 mmHg were identified as independent risk factors by multivariable analysis for AKI. CONCLUSION: The severity of AKI was associated with an increase in the use of healthcare resources after surgery and discharge. Certain risk factors appeared modifiable and may reduce the incidence of AKI and ARF.

Staged Repair of an Aortic Pseudoaneurysm Secondary to Delayed Methylmethacrylate Plate Migration.

Methylmethacrylate is a prosthetic material commonly used for the reconstruction of large chest wall defects. We present the first reported case of delayed methylmethacrylate plate migration, which resulted in an aortic pseudoaneurysm with aortopulmonary fistula. Treatment management, including staged repair combining endovascular and open approaches, is also discussed.

A comparison of pancreaticogastrostomy and pancreaticojejunostomy following pancreaticoduodenectomy.

This retrospective study compares the results of pancreaticogastrostomy (PG) and pancreaticojejunostomy (PJ) in our institution, which has extensive experience in both techniques. Between the years of June 1995 and June 2001, 214 patients underwent pancreaticoduodenectomy (PD) at our institution. Of these 177 had PG and 97 had pancreatojejunostomy (PJ). There were 117 (54.6%) males and 97 (45.3%) females with a mean age of 64.2 +/- 12.4 years. Indications for surgery were pancreatic adenocarcinoma in 101 (47.2%), ampullary adenocarcinoma in 36 (16.9%), distal bile duct adenocarcinoma in 22 (10.2%), duodenal adenocarcinoma in 9 (4.2%), and miscellaneous causes in 46 (21.4%) of patients. Preoperatively, significant differences in the groups were that the patients undergoing PJ were significantly younger than those undergoing PG. Also noted preoperatively, was that the patients undergoing PG had a significantly lower direct bilirubin than those undergoing PJ. With regard to intraoperative parameters, operative time was significantly shorter in the PJ group when compared to the PG group. When the patients who did not develop fistula (N = 186) were compared to those who developed fistula (N = 28) the significant differences were that the patients who developed fistula were more likely to have hypertension preoperatively and a higher alkaline phosphatase. They also showed a significantly higher drain amylase and were likely to have surgery for ampullary, distal bile duct or duodenal carcinoma rather than pancreatic adenocarcinoma. In addition, those patients who developed fistula had a significantly longer postoperative stay, a larger number of intraabdominal abscesses and leaks at the biliary anastomosis. Thirty-day mortality was significantly higher in the PJ group compared to the PG (4 vs. 0, P = 0.041). There was a significantly larger number of bile leaks in the PJ group when compared to the PG (6 vs. 1, P = 0.048). In addition, the PJ group required a significantly larger number of new CT guided drains to control infection (8 vs. 2, P = 0.046) and the PJ group required a larger number of re-explorations to control infection or bleeding (5 vs. 0, P = 0.018). However, the pancreatic fistula rate was not different between the two groups (12% [PG] vs. 14% [PJ]). This retrospective analysis shows that safety of PG can be performed safely and is associated with less complications than PJ and proposes PG as a suitable and safe alternative to PJ for the management of the pancreatic remnant following PD.