Purpose Restrictive allograft syndrome (RAS) is the most severe phenotype of chronic lung allograft dysfunction (CLAD). RAS presents as permanent restrictive lung function decline with typical radiological findings such as apical fibrosis and traction bronchiectasis. We investigated the incidence and clinical impact of RAS-like radiological findings in lung transplant recipients with preserved and stable lung function. Methods 96 adult de novo lung transplant recipients transplanted between 2003-2015 who had not developed CLAD after a median time of 4.8 IQR 4.8 years from transplantation were retrospectively analysed. Serial computed tomography (CT) images were analysed for radiological RAS-like findings. In patients with RAS-like radiological findings, subsequent lung function was determined by spirometry, CLAD diagnosed if FEV1 decreased to <80% of best postoperative, and CLAD subtype and lung volume change was determined by CT volumetry. Results Of 96 lung transplant patients with preserved lung function, 6 (6.3%) had RAS-like signs. These CT findings first occurred at a median of 3.5 IQR 2.0 years after transplantation, initially consisted of apical fibrosis (100%) and later also traction bronchiectasis (50%) (Figure A). During follow-up of median of 5.0 IQR 4.0 years after the first RAS-like signs were seen in CT-images, no lung restriction was detected by CT-volumetry (Figure B), 3/6 patients developed CLAD that was subclassified as BOS, and all 6 patients were alive. Conclusion We detected radiological RAS-like findings in a subpopulation of lung transplant recipients that had preserved and stable lung function. Although some of these patients later develop CLAD, they did not progress to true RAS and had a favourable clinical course. These findings suggest that radiological RAS-like findings in stable lung transplant patients do not always result in rapid lung function decline, restrictive physiology and dismal clinical prognosis associated with true RAS.

International Journal of Laboratory HematologyVolume 40, Issue 5 p. e102-e104 LETTER TO THE EDITOR Combined volume of pulmonary embolism and deep venous thrombosis—Association with FV, platelet count, and D-dimer M. Sane, Corresponding Author M. Sane markus.sane@ksshp.fi orcid.org/0000-0003-1366-9902 Department of Internal Medicine, Jyväskylä Central Hospital, Jyvaskyla, Finland Correspondence Markus Sane, Department of Internal Medicine, Jyväskylä Central Hospital, Jyvaskyla, Finland. Email: markus.sane@ksshp.fiSearch for more papers by this authorJ. A. Laukkanen, J. A. Laukkanen Department of Internal Medicine, Jyväskylä Central Hospital, Jyvaskyla, Finland Department of Clinical Medicine, University of Eastern Finland, Kuopio, FinlandSearch for more papers by this authorM. Granér, M. Granér Heart and Lung Center, Cardiology, Helsinki University Hospital, University of Helsinki, Helsinki, FinlandSearch for more papers by this authorA. Piilonen, A. Piilonen Medical Imaging Center, Radiology, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorM. Raade, M. Raade Docrates Cancer Center, Helsinki, FinlandSearch for more papers by this authorV-P. Harjola, V-P. Harjola Emergency Medicine, University of Helsinki, Helsinki, Finland Department of Emergency Medicine and Services, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorP. Mustonen, P. Mustonen Department of Internal Medicine, Jyväskylä Central Hospital, Jyvaskyla, FinlandSearch for more papers by this author M. Sane, Corresponding Author M. Sane markus.sane@ksshp.fi orcid.org/0000-0003-1366-9902 Department of Internal Medicine, Jyväskylä Central Hospital, Jyvaskyla, Finland Correspondence Markus Sane, Department of Internal Medicine, Jyväskylä Central Hospital, Jyvaskyla, Finland. Email: markus.sane@ksshp.fiSearch for more papers by this authorJ. A. Laukkanen, J. A. Laukkanen Department of Internal Medicine, Jyväskylä Central Hospital, Jyvaskyla, Finland Department of Clinical Medicine, University of Eastern Finland, Kuopio, FinlandSearch for more papers by this authorM. Granér, M. Granér Heart and Lung Center, Cardiology, Helsinki University Hospital, University of Helsinki, Helsinki, FinlandSearch for more papers by this authorA. Piilonen, A. Piilonen Medical Imaging Center, Radiology, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorM. Raade, M. Raade Docrates Cancer Center, Helsinki, FinlandSearch for more papers by this authorV-P. Harjola, V-P. Harjola Emergency Medicine, University of Helsinki, Helsinki, Finland Department of Emergency Medicine and Services, Helsinki University Hospital, Helsinki, FinlandSearch for more papers by this authorP. Mustonen, P. Mustonen Department of Internal Medicine, Jyväskylä Central Hospital, Jyvaskyla, FinlandSearch for more papers by this author First published: 09 June 2018 https://doi.org/10.1111/ijlh.12867Citations: 2Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume40, Issue5October 2018Pages e102-e104 RelatedInformation

Historic treatment strategies in our institute had resulted in 10% Aspergillus mortality within the first posttransplant year. Despite nebulized amphotericin B (nAmB) prophylaxis, a significant incidence of Aspergillus infection, usually with poor outcome, is still reported. The aim of this single-center retrospective study was to evaluate the outcomes of patients receiving either standard nAmB or additional systemic caspofungin prophylaxis for selected high-risk patients. We also tried to define independent risk factors for either fungal infection or death. We followed 76 consecutive lung transplant patients performed at our center between 2002 and 2010 from the day of transplantation. The median follow-up duration was 953 days (2.6 years; range, 16-2,751 days). The endpoints were postoperative Aspergillus colonization or disease or death due to any cause. All patients received either nAmB deoxycholate (nAmBd, 15 patients) or nAmB lipid complex (nAmBLC, 61 patients). In addition, 33 patients also received short-term caspofungin prophylaxis. The overall cumulative mortality during the entire follow up was 14.5%. No clinically confirmed invasive Aspergillus infections (IPA) occurred during the first 2 postoperative years; however, there was 1 possible and 1 probable IPA. One patient died of bronchiolitis obliterans and IPA at 2 years 3 months. Twelve patients showed transient Aspergillus colonization. The antifungal prophylactic regimens were well tolerated. The risk factors for death were age >55 years and postoperative Aspergillus detection (P = .011 and P = .015, respectively). Preoperative Aspergillus colonization/disease was not a risk factor for death (P = 1.000). The strongest predictor of death was age >55 years, due to the elder probably being more susceptible to the adverse effects of immunosuppressants. Postoperative detection of Aspergillus still seems to be an indicator of a poorer outcome. Preoperative Aspergillus colonization is not necessarily a threat with prompt institution of antifungal prophylaxis.

Aims: Our aim was to compare hemostatic and inflammatory mechanisms in abdominal aortic aneurysm (AAA) patients after open surgery (OPEN) and endovascular AAA repair (ENDO). Subjects and Methods: From the 32 consecutive AAA patients recruited, 17 represented ENDO and 15 OPEN. The intra-aneurysmal thrombus was removed during OPEN, but stayed intact after ENDO. The pre-operative volume of the intra-aneurysmal thrombus was calculated from computed tomography images. Markers of coagulation and inflammation were studied pre-operatively, at one, two, three, four and seven days and at three months postoperatively. Results: Preoperative upregulation of F 1 + 2, TAT and D-dimer was evident in both groups. The volume of intra-aneurysmal thrombus correlated with CRP (β=0.62, p=0.001), IL-6 (β=0.60, p=0.001) and PAI-1 ag (β=0.51, p=0.007). Surgery further enhanced inflammation, coagulation and fibrinolysis. IL-6 increased in both groups, but the increases of CRP and PIIINP were higher in the OPEN group. Postoperative CRP correlated with the intra-aneurysmal thrombus volume in the ENDO group. At three months D-dimer (p<0.05) was higher than pre-operatively in the ENDO, in contrast to the OPEN group. Conclusion: Preoperatively both prothrombotic and fibrinolytic mechanisms are activated in patients with AAA. Intraluminal thrombus induces prothrombotic and inflammatory interactions, which persist after endovascular aortic aneurysm repair.

Invasive aspergillosis (IA) is relatively common in allogeneic stem cell transplant (SCT) recipients. Although lungs are the most common site, central nervous system (CNS) involvement is also observed in this setting. We have retrospectively studied 14 cases of CNS aspergillosis found in a cohort of 455 allogeneic SCT recipients (incidence 3%). All patients, except one, had experienced acute graft-versus-host disease treated with high-dose methylprednisolone, and eight patients (57%) had also received ATG. The median time to the diagnosis of CNS aspergillosis was 124 days (range 49-347 days) from SCT. Pulmonary aspergillosis had been diagnosed earlier in four patients (29%). The most common initial symptoms of CNS aspergillosis were convulsions, hemiparesis, and mental alteration. Neuroradiological studies revealed single (two patients) or multiple (seven patients) focal lesions of 0.2-9cm in diameter. Despite clinical suspicion in many patients, a confirmed diagnosis of CNS aspergillosis was made during life in only one patient. A total of 12 patients (86%) received amphotericin B. Despite therapy, all patients died 0-27 days (median seven days) after the initial CNS symptoms. CNS aspergillosis is not uncommon in allogeneic SCT recipients. Clinical manifestations are usually dramatic and progress quickly. Earlier and more effective treatment of IA is needed to prevent dissemination of infection into the CNS.

Lung problems are common in allogeneic stem cell transplant (SCT) recipients. To evaluate the feasibility and diagnostic yield of radiologically guided fine needle lung biopsy (FNLB) in allogeneic SCT recipients with focal pulmonary lesions, a retrospective analysis was carried out. Between 1989 and 1998, radiologists performed a total of 30 FNLBs in 21 allogeneic SCT recipients, guided either by ultrasound (n = 17) or computed tomography (n = 13). The median time from SCT to the first FNLB was 131 days (20-343 days). Prophylactic platelet transfusions were given in 19 procedures (66%). The complications of FNLB included clinically insignificant pneumothorax in four procedures (13%) and self-limiting haemoptysis in one case (3%). The first FNLB was suggestive of invasive pulmonary aspergillosis (IPA) in five patients (24%). Additional clinically useful findings of FNLB included Pseudomonas (two patients) and Nocardia (one patient). The final diagnosis of pulmonary lesions was IPA in 14 patients, immunological lung problems in four patients and other in three patients. Radiologically guided FNLB is feasible in allogeneic SCT recipients and has a low complication rate. The diagnostic yield is high especially for IPA.

OBJECTIVES:The aim of this study was to assess the efficacy and morbidity of radiofrequency thermal ablation of the soft palate in subjects with sleep-disordered breathing.STUDY DESIGN:Prospective, nonrandomized study. Outpatient treatment and an extended follow-up time of 12 months.METHODS:Twenty-one healthy men who were 18 to 60 years of age (median age, 44 y) with sleep-disordered breathing were enrolled to the study. All the patients had habitual snoring for at least 1 year that was associated with excessive daytime sleepiness interfering with social or professional activities. Radiofrequency energy was delivered to the soft palate in two treatment sessions separated by 1 week at 460 +/- 1 kHz with an energy delivery of 600 and 300 J. Snoring Score, Epworth Sleepiness Scale, and cephalometric analysis were measured preoperatively and postoperatively. Certain inflammatory laboratory parameters and visual analogue scale scores of symptoms were measured related to the procedure.RESULTS:The changes in Snoring Score and Epworth Sleepiness Scale scores were statistically significant. The change in the length of the soft palate was statistically significant, whereas the change in palatal width was not. There were no notable changes in the laboratory parameters. The symptom visual analogue scores were low and transient, resolving within days.CONCLUSIONS:The radiofrequency thermal ablation of the soft palate in patients with sleep-disordered breathing seems to be effective. It is safe and associated with only a low morbidity. The promising results must be confirmed in a placebo-controlled study with a larger sample size and a long-term follow-up.

ABSTRACT Mycobacterium triplex, a recently described slowly growing nontuberculous mycobacterium, was isolated from a Finnish patient with pulmonary mycobacteriosis. The disease was successfully treated with antimycobacterial drugs. The strain isolated, which was similar to the type strain but differed slightly from the species description, was regarded as a variant of M. triplex sensu stricto. According to present knowledge this variant of the species has never been isolated before.

Metastases into the temporal bone are uncommon and typically present with trivial otological symptoms. We report a rare case of pulsatile audible tinnitus caused by metastatic breast carcinoma of the temporal bone.

High‐resolution computed tomography (HRCT) has been shown to accurately visualise parenchymal infiltrates of sarcoidosis. The aim of this study was to compare the diagnostic yield (DY) of HRCT with that of endobronchial (EBB) and transbronchial (TBB) biopsies in establishing the diagnosis of sarcoidosis. Forty‐five patients referred to Helsinki University Central Hospital with a presumptive diagnosis of sarcoidosis underwent fiberoptic bronchoscopy (FOB) with bronchoalveolar lavage (BAL), EBB, TBB and HRCT. Thirty‐seven of the patients were diagnosed as having sarcoidosis, 34 of whom showed a parenchymal infiltrate in HRCT. One of the three patients with no parenchymal findings, had positive findings in TBB, and all had lymphocytosis in BAL. The DY for sarcoidosis by EBB and TBB was 24.3% and 50.0%, respectively. The addition of EBB to TBB improved the DY by 8.3%, whereas adding TBB to EBB improved the DY by 30.6%. There were no major complications after the FOB, which was always performed under fluoroscopic control. In conclusion, HRCT is a valuable tool in diagnosing sarcoidosis. However, the HRCT findings cannot be seen in all patients with positive findings in lung biopsy, nor is the parenchymal infiltrate specific for sarcoidosis. Attempting biopsy‐proven diagnosis of sarcoidosis is still recommended. Fiberoptic bronchoscopy with EBB and TBB under fluoroscopic control is a safe and well‐tolerated procedure.

It has been postulated that in severely ill patients splanchnic hypoperfusion may cause endotoxin release from the gut, and this leakage of endotoxin into the circulation can trigger the cascade of inflammatory cytokines. We tested this hypothesis in 9 patients with acute severe pancreatitis by monitoring gastric intramucosal pH (pHi) as measure of splanchnic hypoperfusion at 12-h intervals trying to correlate it to endotoxin and cytokine release. Only 3 of 59 samples, obtained from 3 patients contained circulating endotoxin. Thirteen of 15 plasma samples drawn at pHi <7.20 did not contain endotoxin. The pHi was significantly lower in patients who subsequently developed 3 or more organ failures (P = 0.0017, analysis of variance). Although endotoxemia was only occasionally found, most patients had measurable interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) in their plasma. Concentrations of IL-6, IL-8, and IL-10 on admission correlated to degree of organ dysfunction as measured by the multiple organ system failure score (P = 0.035, r = 0.74; P = 0.010, r = 0.91; P = 0.021, r = 0.82, respectively). In conclusion, patients with acute, severe pancreatitis often have splanchnic hypoperfusion and produce a wide array of cytokines despite a rare occurrence of endotoxemia.

To investigate diagnostic aspects of invasive aspergillosis (IA) in allogeneic BMT recipients, the charts of 22 consecutive patients with IA transplanted in 1989–1995 were reviewed. IA was diagnosed 69–466 days (median 131 days) post BMT. In 16 patients (73%), a definite or probable diagnosis of IA was made during life. Respiratory symptoms were the presenting feature in half of the patients followed by neurological symptoms (27%). Chest X-ray revealed single or multiple nodular lesions in 10 patients; cavitation was observed in five patients. Tissue biopsy was the most common method of diagnosis (nine patients: lungs 6, liver 1, subcutaneous tissue 1, brain 1). Five IA cases were detected by nine guided fine needle lung biopsies in eight patients and without complications. Bronchoalveolar lavage was performed in 14 patients with findings suggestive of invasive pulmonary aspergillosis in eight cases. Lungs were the most common organ affected (90%) followed by central nervous system (41%). The diagnosis of IA is still difficult, and a large number of patients have advanced infection at diagnosis. Methods for early diagnosis are needed. Patients with a clinical suspicion of IA should be treated vigorously with antifungal agents during the diagnostic work-up. Bone Marrow Transplantation (2000) 25, 867–871.

The outcome of invasive aspergillosis (IA) has been considered poor in allogeneic BMT recipients. We analyzed retrospectively the treatment and outcome of IA diagnosed during life in a recent cohort of 20 allogeneic BMT recipients. All patients were initially treated with amphotericin B (AmB) (conventional 16, liposomal 4). Due to toxicity, conventional AmB was changed to a liposomal preparation in 10 patients. Five patients also received itraconazole and three underwent surgery. Of 19 evaluable patients, two patients achieved a complete response and a partial response was observed in five patients (response rate 37%). The median survival was 37 days after the diagnosis. Only two patients (10%) were cured. The prognosis of allogeneic BMT recipients with IA has remained poor. Although treatment responses are common, immunosuppression aggravated by GVHD and its treatment, as well as the commonly disseminated presentation of IA, seem to be major obstacles to the success of therapy. Bone Marrow Transplantation (2000) 26, 759–762.

The aim of this study was to determine whether either natural or recombinant interferon (IFN)-alpha can improve the response to radiotherapy (RT) in patients with small cell lung cancer (SCLC), and to assess the role of IFN in radiation-induced lung injury. All patients had previously participated in a randomised trial of chemotherapy alone or in combination with IFN-alpha in three arms (arm O: no IFN, arm I: natural IFN-alpha, arm II: recombinant IFN-alpha). Patients with locally progressive disease in the lungs following chemotherapy were treated with RT and they continued with their concomitant IFN-alpha. The RT dose was 50 Gy. Radiation-induced lung injury was assessed by lung function tests, computed tomography and bronchoalveolar lavage fluid (BALF) analysis which included cell findings, Interleukin (IL)-1 alpha/-1 beta expression by alveolar macrophages and surfactant components. Seventeen patients were entered in the study, 16 of whom were evaluable. Response rates in Arms O, I and II were 50, 67 and 50%, respectively. Median survival was 18.5, 7 and 23 months respectively, and 1-year survival was 67, 29 and 75% respectively. Long-term survival as assessed by 2- and 3-year survival rates was 29% in patients receiving natural IFN-alpha as compared to 17% in patients not receiving IFN (not statistically significant findings). Every patient had abnormal results when assessed for radiation-induced lung injury. No statistically significant difference was found in toxicity between the treatment arms. A high surfactant protein (SP)-A/phospholipid ratio and a high level of SP-A in BALF before RT was associated with a high degree of radiation-induced lung injury measured by lung function tests and computed tomography in all arms of the study. Thus, we could not show that the combination of IFN-alpha and RT induced more lung toxicity than RT alone as we did in our previous study. The role of high SP-A/phospholipid ratios and high SP-A levels in BALF before RT as predictors of the development of lung injury after RT needs to be determined in the future.

PURPOSE:This prospective clinical study was designed to compare interleukin 1 receptor antagonist (IL-1ra) and E-selectin concentrations in patients with severe acute pancreatitis to those with severe sepsis.MATERIALS AND METHODS:Nine consecutive patients with severe acute pancreatitis and 11 consecutive patients with severe sepsis admitted to a medical/surgical intensive care unit were included in the study. Plasma concentrations of IL-1ra and E-selectin were serially measured daily for 7 days or throughout their stay in the intensive care unit if shorter.RESULTS:The concentrations of IL-1ra were significantly higher on admission in patients with severe sepsis compared with the patients with severe pancreatitis (median levels 10,500 and 2,600 pg/mL, respectively, P = .007). When the data from the first 3 days were analyzed using analysis of variance (ANOVA), the levels of IL-1ra and E-selectin were similar in both groups. The concentrations of IL-1ra and E-selectin correlated to the development of multiorgan dysfunction as assessed by sequential organ failure assessment (SOFA) score (P = .032 and .043, respectively).CONCLUSION:This study shows that IL-1ra and E-selectin are released in acute severe pancreatitis, and the levels seem to be comparable to those in patients with severe sepsis. Concentrations of IL-1ra and E-selectin correlate to the development of multiorgan failure as indicated by high SOFA scores during the first week of disease.

OBJECTIVE:Our aim was to evaluate the development of changes on high-resolution CT (HRCT) associated with chronic pulmonary rejection.MATERIALS AND METHODS:Repeated HRCT examinations were performed 140 times on 13 consecutive lung transplant recipients during a mean observation period of 26 months. The postoperative time interval to the first detection of each chronic change on CT was calculated and compared with the onset of chronic rejection. Bronchiolitis obliterans syndrome (BOS) or the histologic diagnosis of obliterative bronchiolitis was assessed by the published criteria of the International Society for Heart and Lung Transplantation.RESULTS:BOS developed in eight patients, on an average, within 11.6 (+/-5.0) months. Histologic diagnosis was available from five patients. On HRCT, among the first identifiable chronic changes were volume contraction, decreased peripheral vascular and bronchial markings, and thickening of septal lines, all of which appeared between 7 (+/-5.0) and 11 (+/-6.8) months postoperatively. The mean interval for appearance of bronchodilatation was 12.5 (+/-8.7) months. Hyperlucency and mosaic phenomenon were identified, on an average, 16 (+/-6.3) and 21 (+/-7.3) months after transplantation.CONCLUSION:On radiologic monitoring of lung recipients with HRCT, in addition to bronchodilatation. a special attention should be paid to the early chronic changes, including diminution of peripheral bronchovascular markings, thickening of septal lines, and volume reduction, which usually precede the establishment of the diagnosis of chronic rejection, whereas hyperlucency and mosaic phenomenon usually appear during more advanced BOS.

PURPOSE:The plasma levels of prekallikrein, alpha-2-macroglobulin and C1-esterase inhibitor (C1 INH) in patients with previous urticarial reaction to contrast media (CM) were compared to those of a group of nonreacting age- and sex-matched controls. This study evaluated the value of these laboratory variables in predicting acute and delayed urticarial-type reactions.MATERIAL AND METHODS:The study comprised 44 patients (reactors) with acute (n = 29) or delayed (n = 15) urticaria after administration of CM, and a group of age- and sex-matched controls.RESULTS:In the reactors, the levels of prekallikrein and alpha-2-macroglobulin were higher (p < 0.0001) and the level of C1 INH lower (p < 0.0001) than those of the controls. The level of prekallikrein decreased with increasing age (p = 0.02) and women had higher values than men (p = 0.0054). The level of alpha-2-macroglobulin was age-dependent (p = 0.006).CONCLUSION:Although high plasma prekallikrein activity, high plasma alpha-2-macroglobulin activity, and low plasma C1 INH activity are associated with urticaria-type reaction to CM, their value in predicting urticarial reaction is limited because prekallikrein is age- and sex-dependent, and alpha-2-macroglobulin is age-dependent.