Combination of two fat saturation pulses improves detectability of glucose signals in carbon-13 MR spectroscopy

In order to improve the fat suppression performance of in vivo 13C-MRS operating at 3.0 Tesla, a phantom model study was conducted using a combination of two fat suppression techniques; a set of pulses for frequency (chemical shift) selective suppression (CHESS), and spatial saturation (SAT). By optimizing the slab thickness for SAT and the irradiation bandwidth for CHESS, the signals of the –13CH3 peak at 49 ppm and the –13CH2– peak at 26 ppm simulating fat components were suppressed to 5% and 19%, respectively. Combination of these two fat suppression pulses achieved a 53% increase of the height ratio of the glucose C1β peak compared with the sum of all other peaks, indicating better sensitivity for glucose signal detection. This method will be applicable for in vivo 13C-MRS by additional adjustment with the in vivo relaxation times of the metabolites

Allogeneic Hematopoietic Stem Cell Transplantation After Prior Lung Transplantation for Hereditary Pulmonary Alveolar Proteinosis: A Case Report

Pulmonary alveolar proteinosis (PAP) is a rare, diffuse lung disorder characterized by surfactant accumulation in the small airways due to defective clearance by alveolar macrophages, resulting in impaired gas exchange. Whole lung lavage is the current standard of care treatment for PAP. Lung transplantation is an accepted treatment option when whole lung lavage or other experimental treatment options are ineffective, or in case of extensive pulmonary fibrosis secondary to PAP. A disadvantage of lung transplantation is recurrence of PAP in the transplanted lungs, especially in hereditary PAP. The hereditary form of PAP is an ultra-rare condition caused by genetic mutations in genes encoding for the granulocyte macrophage-colony stimulating factor (GM-CSF) receptor, and intrinsically affects bone marrow derived-monocytes, which differentiate into macrophages in the lung. Consequently, these macrophages typically display disrupted GM-CSF receptor-signaling, causing defective surfactant clearance. Bone marrow/hematopoietic stem cell transplantation may potentially reverse the lung disease in hereditary PAP. In patients with hereditary PAP undergoing lung transplantation, post-lung transplant recurrence of PAP may theoretically be averted by subsequent hematopoietic stem cell transplantation, which results in a graft-versus-disease (PAP) effect, and thus could improve long-term outcome. We describe the successful long-term post-transplant outcome of a unique case of end-stage respiratory failure due to hereditary PAP-induced pulmonary fibrosis, successfully treated by bilateral lung transplantation and subsequent allogeneic hematopoietic stem cell transplantation. Our report supports treatment with serial lung and hematopoietic stem cell transplantation to improve quality of life and prolong survival, without PAP recurrence, in selected patients with end-stage hereditary PAP

Mortality after lung transplantation: a single-centre cohort analysis

Detailed data on postoperative death in lung transplant (LTx) recipients are lacking. Therefore, we investigated all deaths after LTx in a large, single-centre, 25-year follow-up cohort. Prevalence, time, place and cause of death (COD) were retrospectively analysed for all patients undergoing primary LTx between July 1991 and December 2015 in our centre. Over subsequent years, postoperative survival significantly improved, with proportionally more patients surviving to 1-year post-LTx (P < 0.0001). A total of 347 (38.9%) LTx recipients died, of which 53.6% expired within 3 years post-LTx [median time to death 910 (236-2447) days]. Autopsy was performed in 34.8% of deaths. COD included CLAD in 27.1% (BOS 63.8% vs. RAS 36.2%); infection (26.5%); malignancy (15.6%); postoperative complication (11.2%); cardiovascular disease (4.6%) or other causes (6.9%). In 8.1%, no clear COD could be determined. COD significantly differed between the various LTx indications (P = 0.047). With longer follow-up, infection becomes a less prevalent COD, but CLAD and malignancies a more important COD. The majority of patients died on the intensive care unit (40.6%) or hospital ward (29.1%), but place of death varied depending on the underlying COD. The current study provides insights into the postoperative deaths of LTx recipients.status: publishe

Flow Controlled Ventilation during EVLP Improves Oxygenation and Preserves Alveolar Recruitment.

PURPOSE: Ex vivo lung perfusion (EVLP) is considered a useful platform to evaluate, preserve and recondition grafts prior to lung transplantation (LTx). Reducing physical stress due to standard volume-controlled ventilation (VCV), might further prolong EVLP in time and reduce ventilator induced lung injury (VILI). An innovative approach might be the use of flow-controlled ventilation (FCV), a ventilation mode which controls inspiratory and expiratory flow. These properties can reduce atelectrauma and volutrauma related to standard VCV. This is the first study to evaluate the use of FCV during EVLP in a porince model. METHODS: Porcine lungs were mounted on EVLP after 2 hours of warm ischemia and divided into 2 groups (n=7/group). EVLP was maintained for 6 hours and physiological parameters were continuously recorded. In the first group, lungs on EVLP were ventilated standardly (VCV, 7 ml/kg). In the second group, lungs were ventilated using FCV (7ml/kg). After EVLP, W/D ratios were taken of the right lung and the left lung was frozen while inflated in liquid nitrogen vapors and CT scanned. RESULTS: Results are demonstrated in figure 1. Pulmonary vascular resistance (PVR) was comparable between VCV and FCV (p=0.52). FCV significantly increased oxygenation (P/F ratios) (p=0.01), and better maintained dynamic compliance (p=0.03). There was no difference in W/D ratios between the groups (p=0.16). CT density measurements were decreased by FCV (p=0.05). CONCLUSION: FCV is feasible to ventilate pulmonary grafts during EVLP and improves oxygenation. The lower decline in compliance and lower CT density measurements in FCV might indicate a better preservation of alveolar recruitment since extravascular water content (W/D ratio) was similar between both groups. In conclusion, FCV ventilation might reduce injury related to standard volume-controlled ventilation. Using FCV mode during EVLP might stabilize and prolong EVLP time in the future and open the perspective to further actively recondition grafts.status: publishe

Validation and verification of examination procedures in medical laboratories: Opinion of the EFLM Working Group Accreditation and ISO/CEN standards (WG-A/ISO) on dealing with ISO 15189:2012 demands for method verification and validation

This paper reflects the opinion of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group Accreditation and ISO/CEN standards (WG-A/ISO). It aims to provide guidance for drawing up local/national documents about validation and verification of laboratory methods. We demonstrate how risk evaluation can be used to optimize laboratory policies to meet intended use requirements as well as requirements of standards. This is translated in a number of recommendations on how to introduce risk evaluation in various stages of the implementation of new methods ultimately covering the whole process cycle. © 2020 Walter de Gruyter GmbH, Berlin/Boston