Bridge to Thoracic Organ Transplantation in Patients with Pulmonary Arterial Hypertension Using a Pumpless Lung Assist Device

We describe a novel technique of pumpless extracorporeal life support in four patients with cardiogenic shock due to end-stage pulmonary hypertension (PH) including patients with veno-occlusive disease (PVOD) using a pumpless lung assist device (LAD). The device was connected via the pulmonary arterial main trunk and the left atrium, thereby creating a septostomy-like shunt with the unique addition of gas exchange abilities in parallel to the lung. Using this approach, all four patients were successfully bridged to bilateral lung transplantation and combined heart–lung transplantation, respectively. Although all patients presented in cardiogenic shock, hemodynamic unloading of the right ventricle using the low-resistance LAD stabilized the hemodynamic situation immediately so that no pump support was subsequently required.     

MMP-Dependent Migration of Extrapulmonary Myofibroblast Progenitors Contributing to Posttransplant Airway Fibrosis in the Lung

Myofibroblasts play a central role in fibroproliferative airway remodeling in obliterative bronchiolitis (OB) after lung transplantation. The purpose of the study is to elucidate the mechanisms whereby matrix metalloproteinases (MMPs) contribute to myofibroblast-mediated allograft airway fibrosis. In an intrapulmonary tracheal transplant model of OB, broad-spectrum MMP inhibitors, SC080 and MMI270 reduced the number of myofibroblasts at day 28 without changing differentiation, proliferation or apoptosis of myofibroblasts or fibroblasts. Next, myofibroblasts in allograft airway fibrosis were demonstrated to be almost exclusively of extrapulmonary origin by analyzing RT1Aⁿ positive myofibroblasts in an animal model combining orthotopic lung transplantation (from Lewis (RT1A^l) to F1 (Brown–Norway (RT1Aⁿ) × Lewis)) and intrapulmonary tracheal transplantation (from a Wister–Furth rat (RT1A^u) into the transplanted Lewis-derived lung). Using peripheral blood mononuclear cells (PBMCs) that can differentiate into α-SMA positive myofibroblasts in vitro , we demonstrated their contribution to the myofibroblast population of allograft airway fibrosis in vivo using a fluorescence-labeling cell tracking system. Moreover, PBMC-derived fibroblast-like cells expressed high levels of MMP-9 and MMP-12 and their migration was inhibited by MMP inhibitors in a wound healing assay. In conclusion, MMP-dependent migration of PBMC-derived myofibroblast precursors is an important contributing mechanism to the development of allograft airway fibrosis.     

Medicine and money: the ethical transformation of medical practice

OBJECTIVE: To explore the generalised application of a discourse of cost reduction in the practice of medicine in the USA. CONTEXT: Changes in the health services industry over the last 20 years have left much concern in the hearts and minds of many, providers and patients alike. Even for the millions of Americans who are able to purchase health insurance, the standard of care has changed. In some ways, the current managed-care climate has created an atmosphere of distrust between patients and their providers, and, more significantly, a general sense of dissatisfaction with the state of health care in the USA. In the midst of this discontent, health providers have begun to question their own roles in what is increasingly a for-profit health care system. Not surprisingly, medical educators now question whether the current health system is creating a new generation of doctors who are concerned with reducing costs without adequate review of clinical data. METHODS: This paper examines the rationale applied in the management of a patient with end-stage liver disease in a teaching hospital. The case is re-socialised by situating it in an ethical discourse linked to the function of the for-profit health system. RESULTS: The decision about whether to give human albumin to an insured patient serves as a lens through which to examine how uncritical appeals to the discourse of 'cost-effectiveness' can supersede a patient- and data-oriented approach to medical decision making. CONCLUSIONS: This case illustrates the permeation of economic considerations into the core values of medicine, highlighting a detrimental ethical shift occurring in the field. The training of new doctors represents a site from which to resist this unwelcome transformation.     

15 years single center experience with surgical resection of the superior vena cava for non-small cell lung cancer

OBJECTIVES: To examine our results with surgery for locally advanced non-small cell lung cancer (NSCLC) invading the superior vena cava (SVC). METHODS: A retrospective analysis of patients who underwent resection between 1988 and 2003 was performed. Postoperative morbidity, long-term survival, including risk factors for overall and disease-free survival were examined. RESULTS: Median age of the 15 operated patients was 60 years (28-78). All had direct SVC invasion by tumor. All underwent mediastinoscopy. Seven patients with N2 disease, and one with a bulky right upper lobe tumor received induction therapy. Eight underwent lobectomy (three sleeve), and seven had pneumonectomy (two carinal). The SVC was replaced by interposition graft in nine patients, whereas six had partial resection. There were two postoperative deaths (14%) and three major morbidities (23%). There was one late graft thrombosis. Mean follow-up was 25 months (3-132, median 11). Overall 1 and 3-year survival was 68 and 57% and disease-free survival was 55 and 27%, respectively. All late deaths were due to recurrence. Survival of patients with N2 disease was not significantly worse than those with localized (N0/N1) nodal disease. There was a trend towards later recurrence in patients who had induction therapy (median disease-free interval of 29 months versus 5 months in the untreated group, P = 0.3), but there was no significant effect on overall survival. The extent of lung resection and type of SVC procedure did not influence long-term survival. CONCLUSIONS: Carefully selected patients with NSCLC and SVC involvement can be operated upon with acceptable postoperative morbidity and mortality. Induction therapy appears to delay recurrence.     

Lung transplantation: donor and recipient critical care aspects

PURPOSE OF REVIEW: The purpose of this paper is to highlight new developments in donor and recipient lung transplant issues for the critical care physician. RECENT FINDINGS: A shortage of suitable lung donors has led to the use of extended donors and the development of novel techniques such as live-donor lung transplantation and the use of non-heart-beating donors. The increased experience and success with lung transplantation has also resulted in the extension of this therapy to patients previously considered unsuitable for transplantation. Postoperative outcomes can be affected by many of these recent donor and recipient changes. Improved preservation solutions and techniques to reduce reperfusion injury may be able to ameliorate some of the new perioperative graft dysfunction, but morbidity is still potentially significant, and extraordinary interventions such as extracorporeal membrane oxygenation may be required in selected cases. SUMMARY: Patients undergoing lung transplantation continue to be very challenging in the intensive care unit. A multidisciplinary approach to care, and early recognition of serious problems, will help improve outcomes.     

The effect of low-potassium-dextran versus Euro-Collins solution for preservation of isolated type II pneumocytes.

Limited availability of donor organs is a major factor restricting the clinical application of lung transplantation. Improvements in preservation techniques are essential for prolonging storage time and improving lung function following transplantation. The present investigation used primary cultures of adult rat alveolar type II cells as a model for evaluating lung-preservation solutions. Type II cells were plated onto tissue-culture plastic at a density 5 x 10(5) cells/cm2 and maintained in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum (D10) for 40 hr. Cells were then exposed to Euro-Collins solution or a low-potassium-dextran solution (LPD). At designated time points, measurements of lactate-dehydrogenase (LDH) release, protein content, and incorporation of 3H-thymidine into cellular DNA were made. During 12 hr of "storage" at 37 degrees C, cells maintained in LPD released less LDH (14.3 +/- 1.2% of cellular total, mean +/- SEM, n = 5) than their counterparts stored in EC (20.6 +/- 1.6%, P less than 0.05). During the 36 hr following a 6-hr exposure to preservative solutions, LPD-treated cells incorporated more thymidine per mg of protein (2566 +/- 419.8 cpm/micrograms protein, mean +/- SEM, n = 6) compared with cells maintained continuously in D10 (1431 +/- 351, P less than 0.05). By contrast, cells exposed to EC incorporated less thymidine (82.2 +/- 62.8 cpm/micrograms protein) than either cells maintained in LPD or D10 (P less than 0.01 for each comparison). These results suggest that LPD solution is less cytotoxic than EC and that LPD enables higher levels of metabolic activity in recovering epithelial cells. In vitro cultures of type II epithelial cells are a useful model system for the study of lung preservation and posttransplantation lung injury.     

A structured community engagement strategy to support uptake of TB active case-finding

BACKGROUND:In Lima, Peru, a mobile TB screening program (“TB Móvil”) was implemented in high TB prevalence districts to increase TB screening. Community engagement activities to promote TB Móvil were simultaneously conducted.OBJECTIVE:To describe a structured, theory-driven community engagement strategy to support the uptake of TB Móvil.METHODS:We adapted Popular Opinion Leader (POL), an evidence-based social networking intervention previously used in Peru to promote HIV testing, for TB Móvil. Community health workers, women who run soup kitchens, and motorcycle taxi drivers served as “popular opinion leaders” who disseminated information about TB Móvil in everyday conversations, aided by a multi-media campaign. Performance indicators of POL included the number/characteristics of persons screened; number of multimedia elements; and proportion of persons with abnormal radiographs hearing about TB Móvil before attending.RESULTS:Between February 2019 and January 2020, 63,899 people attended the TB Móvil program at 210 sites; 60.1% were female. The multimedia campaign included 36 videos, 16 audio vignettes, flyers, posters, community murals and “jingles.” Among attendees receiving an abnormal chest X-ray suggestive of TB, 48% (6,935/14,563) reported hearing about TB Móvil before attending.CONCLUSIONS:POL promotes the uptake of TB Móvil and should be considered as a strategy for increasing TB screening uptake.