A method for translational rat ex vivo lung perfusion experimentation

The application of ex vivo lung perfusion (EVLP) has significantly increased the successful clinical use of marginal donor lungs. While large animal EVLP models exist to test new strategies to improve organ repair, there is currently no rat EVLP model capable of maintaining long-term lung viability. Here, we describe a new rat EVLP model that addresses this need, while enabling the study of lung injury due to cold ischemic time (CIT). The technique involves perfusing and ventilating male Lewis rat donor lungs for 4 h before transplanting the left lung into a recipient rat and then evaluating lung function 2 h after reperfusion. To test injury within this model, lungs were divided into groups and exposed to different CITs (i.e., 20 min, 6 h, 12 h, 18 h and 24 h). Experiments involving the 24-h-CIT group were prematurely terminated due to the development of severe edema. For the other groups, no differences in the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO₂/FIO₂) were observed during EVLP; however, lung compliance decreased over time in the 18-h group (P = 0.012) and the PaO₂/FIO₂ of the blood from the left pulmonary vein 2 h after transplantation was lower compared with 20-min-CIT group (P = 0.0062). This new model maintained stable lung function during 4-h EVLP and after transplantation when exposed to up to 12 h of CIT

Improved results of induction chemoradiation before surgical intervention for selected patients with stage IIIA-N2 non–small cell lung cancer

ObjectiveOptimal management of stage IIIA-N2 non–small cell lung cancer remains controversial. The surgical arm of the North American Intergroup 0139 trial was adopted as the standard treatment for patients with resectable N2 disease at the University Health Network. Results after 7 years of experience are reported.MethodsThis is a retrospective study of consecutive patients with biopsy-proved T1-3 N2 M0 lung cancer who underwent induction chemoradiation before surgical intervention from January 1997 through August 2004. Induction chemotherapy consisted of cisplatin, 50 mg/m2, on days 1 and 8; etoposide, 50 mg/m2, on days 1 to 5, weeks 1 and 5; and concurrent daily external beam radiotherapy to 45 Gy. Lung resection was performed within 6 weeks of completion of chemoradiation, followed by 2 further cycles of consolidation chemotherapy.ResultsBetween January 1997 and August 2004, 40 patients were treated according to this protocol (25% T1, 62.5% T2, 7.5% T3, and 5% T4). Overall and disease-free median survivals were 40 and 37.1 months, respectively, whereas overall and disease-free 3-year survivals were 51.7% and 52.3%, respectively. R0 resection was achieved in 92.5%. The overall operative mortality rate was 7.5% (0% for lobectomy and 27% for pneumonectomy). Notably, all mortalities occurred within the first 2 years of our experience with this regimen.ConclusionChemoradiation before pulmonary resection in carefully selected patients with surgically resectable stage IIIA (N2) non–small cell lung cancer can lead to improved overall and disease-free survival

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment

In this Policy Forum piece, Aditya Narayan and colleagues discuss the challenges and opportunities for tuberculosis preventive treatment in carceral settings

Drug-Resistant Tuberculosis Control in China: Progress and Challenge

Background: China has the second highest caseload of multidrug-resistant tuberculosis (MDR-TB) in the world. In 2009, the Chinese government agreed to draw up a plan for MDR-TB prevention and control in the context of a comprehensive health system reform launched in the same year. Discussion: China is facing high prevalence rates of drug-resistant TB and MDR-TB. MDR-TB disproportionally affects the poor rural population and the highest rates are in less developed regions largely due to interrupted and/or inappropriate TB treatment. Most households with an affected member suffer a heavy financial burden because of a combination of treatment and other related costs. The influential Global Fund programme for MDR-TB control in China provides technical and financial support for MDR-TB diagnosis and treatment. However, this programme has a fixed timeline and cannot provide a long term solution. In 2009, the Bill and Melinda Gates Foundation, in cooperation with the National Health and Family Planning Commission of China, started to develop innovative approaches to TB/MDR-TB management and case-based payment mechanisms for treatment, alongside increased health insurance benefits for patients, in order to contain medical costs and reduce financial barriers to treatment. Although these efforts appear to be in the right direction, they may not be sufficient unless (a) domestic sources are mobilized to raise funding for TB/MDR-TB prevention and control and (b) appropriate incentives are given to both health facilities and their care providers. Summary: Along with the on-going Chinese health system reform, sustained government financing and social health protection schemes will be critical to ensure universal access to appropriate TB treatment in order to reduce risk of developing MDR-TB and systematic MDR-TB treatment and management

Integrating a health-related-quality-of-life module within electronic health records: a comparative case study assessing value added

<p>Abstract</p> <p>Background</p> <p>Health information technology (HIT) applications that incorporate point-of-care use of health-related quality of life (HRQL) assessments are believed to promote patient-centered interactions between seriously ill patients and physicians. However, it is unclear how willing primary care providers are to use such HRQL HIT applications. The specific aim of this study was to explore factors that providers consider when assessing the value added of an HRQL application for their geriatric patients.</p> <p>Methods</p> <p>Three case studies were developed using the following data sources: baseline surveys with providers and staff, observations of staff and patients, audio recordings of patient-provider interactions, and semi-structured interviews with providers and staff.</p> <p>Results</p> <p>The primary factors providers considered when assessing value added were whether the HRQL information from the module was (1) duplicative of information gathered via other means during the encounter; (2) specific enough to be useful and/or acted upon, and; (3) useful for enough patients to warrant time spent reviewing it for all geriatric patients. Secondary considerations included level of integration of the HRQL and EHR, impact on nursing workflow, and patient reluctance to provide HRQL information.</p> <p>Conclusions</p> <p>Health-related quality of life modules within electronic health record systems offer the potential benefit of improving patient centeredness and quality of care. However, the modules must provide benefits that are substantial and prominent in order for physicians to decide that they are worthwhile and sustainable. Implications of this study for future research include the identification of perceived "costs" as well as a foundation for operationalizing the concept of "usefulness" in the context of such modules. Finally, developers of these modules may need to make their products customizable for practices to account for variation in EHR capabilities and practice workflows.</p

Correction to:Expanding controlled donation after the circulatory determination of death: statement from an international collaborative (Intensive Care Medicine, (2021), 47, 3, (265-281), 10.1007/s00134-020-06341-7)

The article “Expanding controlled donation after the circulatory determination of death: statement from an international collaborative”, written by Domínguez-Gil, B., Ascher, N., Capron, A.M. et al. was originally published electronically on the publisher’s internet portal on 21 February 2021 without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on 25 March 2021 to © The Author(s) 2021 and the article is forthwith distributed under a Creative Commons Attribution this article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/. The original article has been corrected

Predictors of Multidrug- and Extensively Drug-Resistant Tuberculosis in a High HIV Prevalence Community

BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) have emerged in high-HIV-prevalence settings, which generally lack laboratory infrastructure for diagnosing TB drug resistance. Even where available, inherent delays with current drug-susceptibility testing (DST) methods result in clinical deterioration and ongoing transmission of MDR and XDR-TB. Identifying clinical predictors of drug resistance may aid in risk stratification for earlier treatment and infection control. METHODS: We performed a retrospective case-control study of patients with MDR (cases), XDR (cases) and drug-susceptible (controls) TB in a high-HIV-prevalence setting in South Africa to identify clinical and demographic risk factors for drug-resistant TB. Controls were selected in a 1:1:1 ratio and were not matched. We calculated odds ratios (OR) and performed multivariate logistic regression to identify independent predictors. RESULTS: We enrolled 116, 123 and 139 patients with drug-susceptible, MDR, and XDR-TB. More than 85% in all three patient groups were HIV-infected. In multivariate analysis, MDR and XDR-TB were each strongly associated with history of TB treatment failure (adjusted OR 51.7 [CI 6.6-403.7] and 51.5 [CI 6.4-414.0], respectively) and hospitalization more than 14 days (aOR 3.8 [CI 1.1-13.3] and 6.1 [CI 1.8-21.0], respectively). Prior default from TB treatment was not a risk factor for MDR or XDR-TB. HIV was a risk factor for XDR (aOR 8.2, CI 1.3-52.6), but not MDR-TB. Comparing XDR with MDR-TB patients, the only significant risk factor for XDR-TB was HIV infection (aOR 5.3, CI 1.0-27.6). DISCUSSION: In this high-HIV-prevalence and drug-resistant TB setting, a history of prolonged hospitalization and previous TB treatment failure were strong risk factors for both MDR and XDR-TB. Given high mortality observed among patients with HIV and drug-resistant TB co-infection, previously treated and hospitalized patients should be considered for empiric second-line TB therapy while awaiting confirmatory DST results in settings with a high-burden of MDR/XDR-TB

Pharmacologic targeting of renal ischemia-reperfusion injury using a normothermic machine perfusion platform.

Normothermic machine perfusion (NMP) is an emerging modality for kidney preservation prior to transplantation. NMP may allow directed pharmacomodulation of renal ischemia-reperfusion injury (IRI) without the need for systemic donor/recipient therapies. Three proven anti-IRI agents not in widespread clinical use, CD47-blocking antibody (αCD47Ab), soluble complement receptor 1 (sCR1), and recombinant thrombomodulin (rTM), were compared in a murine model of kidney IRI. The most effective agent was then utilized in a custom NMP circuit for the treatment of isolated porcine kidneys, ascertaining the impact of the drug on perfusion and IRI-related parameters. αCD47Ab conferred the greatest protection against IRI in mice after 24 hours. αCD47Ab was therefore chosen as the candidate agent for addition to the NMP circuit. CD47 receptor binding was demonstrated by immunofluorescence. Renal perfusion/flow improved with CD47 blockade, with a corresponding reduction in oxidative stress and histologic damage compared to untreated NMP kidneys. Tubular and glomerular functional parameters were not significantly impacted by αCD47Ab treatment during NMP. In a murine renal IRI model, αCD47Ab was confirmed as a superior anti-IRI agent compared to therapies targeting other pathways. NMP enabled effective, direct delivery of this drug to porcine kidneys, although further efficacy needs to be proven in the transplantation setting

Treatment Outcomes of Multidrug-Resistant Tuberculosis: A Systematic Review and Meta-Analysis

BACKGROUND:Treatment outcomes for multidrug-resistant Mycobacterium Tuberculosis (MDRTB) are generally poor compared to drug sensitive disease. We sought to estimate treatment outcomes and identify risk factors associated with poor outcomes in patients with MDRTB. METHODOLOGY/PRINCIPAL FINDINGS:We performed a systematic search (to December 2008) to identify trials describing outcomes of patients treated for MDRTB. We pooled appropriate data to estimate WHO-defined outcomes at the end of treatment and follow-up. Where appropriate, pooled covariates were analyzed to identify factors associated with worse outcomes. Among articles identified, 36 met our inclusion criteria, representing 31 treatment programmes from 21 countries. In a pooled analysis, 62% [95% CI 57-67] of patients had successful outcomes, while 13% [9]-[17] defaulted, 11% [9]-[13] died, and 2% [1]-[4] were transferred out. Factors associated with worse outcome included male gender 0.61 (OR for successful outcome) [0.46-0.82], alcohol abuse 0.49 [0.39-0.63], low BMI 0.41[0.23-0.72], smear positivity at diagnosis 0.53 [0.31-0.91], fluoroquinolone resistance 0.45 [0.22-0.91] and the presence of an XDR resistance pattern 0.57 [0.41-0.80]. Factors associated with successful outcome were surgical intervention 1.91 [1.44-2.53], no previous treatment 1.42 [1.05-1.94], and fluoroquinolone use 2.20 [1.19-4.09]. CONCLUSIONS/SIGNIFICANCE:We have identified several factors associated with poor outcomes where interventions may be targeted. In addition, we have identified high rates of default, which likely contributes to the development and spread of MDRTB