Long COVID is associated with severe cognitive slowing: a multicentre cross-sectional study.

Background: COVID-19 survivors may experience a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing. Methods: To examine cognitive slowing, patients with PCC completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). All patients with PCC completed the study between May 18, 2021 and July 4, 2023 in Jena University Hospital, Jena, Germany and Long COVID clinic, Oxford, UK. Findings: We identified pronounced cognitive slowing in patients with PCC, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-s task measuring simple reaction time (SRT), with patients with PCC responding to stimuli ∼3 standard deviations slower than healthy controls. 53.5% of patients with PCC's response speed was slower than 2 standard deviations from the control mean, indicating a high prevalence of cognitive slowing in PCC. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in patients with PCC. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of patients with PCC on the NVT measure of sustained attention. Interpretation: Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in patients with PCC. Funding: Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890).

Functional Impairment in Small Airways Associated With the Breathlessness Symptoms in Long-Coronavirus Disease.

PURPOSE: This study aimed to determine the association between functional impairment in small airways and symptoms of dyspnea in patients with Long-coronavirus disease (COVID), using imaging and computational modeling analysis. PATIENTS AND METHODS: Thirty-four patients with Long-COVID underwent thoracic computed tomography and hyperpolarized Xenon-129 magnetic resonance imaging (HP Xe MRI) scans. Twenty-two answered dyspnea-12 questionnaires. We used a computed tomography-based full-scale airway network (FAN) flow model to simulate pulmonary ventilation. The ventilation distribution projected on a coronal plane and the percentage lobar ventilation modeled in the FAN model were compared with the HP Xe MRI data. To assess the ventilation heterogeneity in small airways, we calculated the fractal dimensions of the impaired ventilation regions in the HP Xe MRI and FAN models. RESULTS: The ventilation distribution projected on a coronal plane showed an excellent resemblance between HP Xe MRI scans and FAN models (structure similarity index: 0.87 ± 0.04). In both the image and the model, the existence of large clustered ventilation defects was not identifiable regardless of dyspnea severity. The percentage lobar ventilation of the HP Xe MRI and FAN model showed a strong correlation (ρ = 0.63, P < 0.001). The difference in the fractal dimension of impaired ventilation zones between the low and high dyspnea-12 score groups was significant (HP Xe MRI: 1.97 [1.89 to 2.04] and 2.08 [2.06 to 2.14], P = 0.005; FAN: 2.60 [2.59 to 2.64] and 2.64 [2.63 to 2.65], P = 0.056). CONCLUSIONS: This study has identified a potential association of small airway functional impairment with breathlessness in Long-COVID, using fractal analysis of HP Xe MRI scans and FAN models.

Neutrophil levels correlate with quantitative extent and progression of fibrosis in IPF: results of a single-centre cohort study.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with poor prognosis. Clinical studies have demonstrated association between different blood leucocytes and mortality and forced vital capacity (FVC) decline. Here, we question which blood leucocyte levels are specifically associated with progression of fibrosis, measured by accumulation of fibrosis on CT scan using a standardised automated method. METHODS: Using the Computer-Aided Lung Informatics for Pathology Evaluation and Rating CT algorithm, we determined the correlation between different blood leucocytes (<4 months from CT) and total lung fibrosis (TLF) scores, pulmonary vessel volume (PVV), FVC% and transfer factor of lung for carbon monoxide% at baseline (n=171) and with progression of fibrosis (n=71), the latter using multivariate Cox regression. RESULTS: Neutrophils (but not monocyte or lymphocytes) correlated with extent of lung fibrosis (TLF/litre) (r=0.208, p=0.007), PVV (r=0.259, p=0.001), FVC% (r=-0.127, p=0.029) at baseline. For the 71 cases with repeat CT; median interval between CTs was 25.9 (16.8-39.9) months. Neutrophil but not monocyte levels are associated with increase in TLF/litre (HR 2.66, 95% CI 1.35 to 5.25, p=0.005). CONCLUSION: Our study shows that neutrophil rather than monocyte levels correlated with quantifiable increase in fibrosis on imaging of the lungs in IPF, suggesting its relative greater contribution to progression of fibrosis in IPF.

Psychosocial treatments for nightmares in adults and children: a systematic review.

BACKGROUND: As nightmares may be a risk factor for, or symptom of, multiple psychological disorders, some researchers suggest that nightmares should be screened, diagnosed, and treated. Treatments for nightmares include trauma-focused Cognitive Behavioural Therapy and Image Rehearsal Therapy, and pharmacological interventions such as prazosin and nitrazepam. As recent research has put into question our current understanding of treatment efficacy, there is a need to systematically review findings related to the effectiveness of nightmare treatments to inform best practice. The current review assessed the efficacy of psychosocial treatments of nightmare in all cohorts. METHODS: A systematic search of four databases for peer reviewed journal articles from 2000 onwards produced 69 (35 RCTs, 34 non-RCTs) eligible articles that underwent narrative synthesis. RESULTS: The results provide strong evidence for exposure and image rehearsal treatments for the reduction of nightmare frequency, severity, and distress, in civilian, military, idiopathic, and posttraumatic stress disorder (PTSD) cohorts. There is emerging evidence that self-guided and brief treatment modalities offer efficient and effective treatment options. There is an urgent need for clinical trials of treatment effectiveness in children. CONCLUSIONS: The results suggest that treatments for nightmares are most effective when they facilitate a sense of control or mastery by directly targeting the nightmare content and/or the client's emotional responses to the nightmare content. TRIAL REGISTRATION: A review protocol was registered with PROSPERO (CRD42020204861).

Persistence of inflammatory and vascular mediators 5 months after hospitalization with COVID-19 infection.

Background and aim: In acute severe COVID-19, patients present with lung inflammation and vascular injury, accompanied by an exaggerated cytokine response. In this study, our aim was to describe the inflammatory and vascular mediator profiles in patients who were previously hospitalized with COVID-19 pneumonitis, months after their recovery, and compare them with those in patients recovering from severe sepsis and in healthy controls. Methods: A total of 27 different cytokine, chemokine, vascular endothelial injury and angiogenic mediators were measured in the plasma of forty-nine patients 5.0 ± 1.9 (mean ± SD) months after they were hospitalized with COVID-19 pneumonia, eleven patients 5.4 ± 2.9 months after hospitalization with acute severe sepsis, and 18 healthy controls. Results: Compared with healthy controls, IL-6, TNFα, SAA, CRP, Tie-2, Flt1, and PIGF were significantly increased in the post-COVID group, and IL-7 and bFGF were significantly reduced. While IL-6, PIGF, and CRP were also significantly elevated in post-Sepsis patients compared to controls, the observed differences in TNFα, Tie-2, Flt-1, IL-7 and bFGF were unique to the post-COVID group. TNFα levels significantly correlated with the severity of acute COVID-19 illness (spearman's r = 0.30, p < 0.05). Furthermore, in post-COVID patients, IL-6 and CRP were each strongly negatively correlated with gas transfer factor %predicted (spearman's r = -0.51 and r = -0.57, respectively, p < 0.002) and positively correlated with computed tomography (CT) abnormality scores at recovery (r = 0.28 and r = 0.46, p < 0.05, respectively). Conclusion: A unique inflammatory and vascular endothelial damage mediator signature is found in plasma months following acute COVID-19 infection. Further research is required to determine its pathophysiological and clinical significance.

Increased monocyte level is a risk factor for radiological progression in patients with early fibrotic interstitial lung abnormality.

Background: Interstitial lung abnormalities (ILA) are specific spatial patterns on computed tomography (CT) scan potentially compatible with early interstitial lung disease. A proportion will progress; management involves risk stratification and surveillance. Elevated blood monocyte levels have been shown to associate with progression of idiopathic pulmonary fibrosis. The aims of the present study were: 1) to estimate the proportion of "early fibrotic" (EF)-ILAs (reticular±ground-glass opacities, excluding traction bronchiectasis and honeycombing) on CT scans of patients attending all-indications thoracic CTs, and proportion demonstrating radiological progression; and 2) to explore association between peripheral blood leukocyte levels and ILA progression. Methods: We analysed all thoracic CT reports in individuals aged 45-75 years performed between January 2015 and December 2020 in one large teaching hospital (Oxford, UK) to identify patient CT reports consistent with EF-ILA. CT-contemporaneous blood leukocyte counts were examined to explore contribution to progression and all-cause mortality, using multivariate Cox regression. Results: 40 711 patients underwent thoracic CT imaging during this period. 1259 (3.1%) demonstrated the EF-ILA pattern (mean±sd age 65.4±7.32 years; 735 (47.8%) male). EF-ILA was significantly associated with all-cause mortality (hazard ratio 1.87, 95% CI 1.25-2.78; p=0.002). 362 cases underwent at least one follow-on CT. Radiological progression was observed in 157 (43.4%) cases: increase in reticulation n=51, new traction bronchiectasis n=84, honeycombing n=22. Monocyte count, neutrophil count, monocyte:lymphocyte ratio, neutrophil:lymphocyte ratio and "systemic inflammatory response index" were significantly associated with radiological progression. Conclusion: 3.1% of subjects requiring thoracic CT during a 6-year period demonstrated EF-ILA. Monocyte levels and blood leukocyte-derived indexes were associated with radiological progression and could indicate which patients may require closer follow-up.

Lung Abnormalities Detected with Hyperpolarized 129Xe MRI in Patients with Long COVID.

Background Post-COVID-19 condition encompasses symptoms following COVID-19 infection that linger at least 4 weeks after the end of active infection. Symptoms are wide ranging, but breathlessness is common. Purpose To determine if the previously described lung abnormalities seen on hyperpolarized (HP) pulmonary xenon 129 (129Xe) MRI scans in participants with post-COVID-19 condition who were hospitalized are also present in participants with post-COVID-19 condition who were not hospitalized. Materials and Methods In this prospective study, nonhospitalized participants with post-COVID-19 condition (NHLC) and posthospitalized participants with post-COVID-19 condition (PHC) were enrolled from June 2020 to August 2021. Participants underwent chest CT, HP 129Xe MRI, pulmonary function testing, and the 1-minute sit-to-stand test and completed breathlessness questionnaires. Control subjects underwent HP 129Xe MRI only. CT scans were analyzed for post-COVID-19 interstitial lung disease severity using a previously published scoring system and full-scale airway network (FAN) modeling. Analysis used group and pairwise comparisons between participants and control subjects and correlations between participant clinical and imaging data. Results A total of 11 NHLC participants (four men, seven women; mean age, 44 years ± 11 [SD]; 95% CI: 37, 50) and 12 PHC participants (10 men, two women; mean age, 58 years ±10; 95% CI: 52, 64) were included, with a significant difference in age between groups (P = .05). Mean time from infection was 287 days ± 79 (95% CI: 240, 334) and 143 days ± 72 (95% CI: 105, 190) in NHLC and PHC participants, respectively. NHLC and PHC participants had normal or near normal CT scans (mean, 0.3/25 ± 0.6 [95% CI: 0, 0.63] and 7/25 ± 5 [95% CI: 4, 10], respectively). Gas transfer (Dlco) was different between NHLC and PHC participants (mean Dlco, 76% ± 8 [95% CI: 73, 83] vs 86% ± 8 [95% CI: 80, 91], respectively; P = .04), but there was no evidence of other differences in lung function. Mean red blood cell-to-tissue plasma ratio was different between volunteers (mean, 0.45 ± 0.07; 95% CI: 0.43, 0.47]) and PHC participants (mean, 0.31 ± 0.10; 95% CI: 0.24, 0.37; P = .02) and between volunteers and NHLC participants (mean, 0.37 ± 0.10; 95% CI: 0.31, 0.44; P = .03) but not between NHLC and PHC participants (P = .26). FAN results did not correlate with Dlco) or HP 129Xe MRI results. Conclusion Nonhospitalized participants with post-COVID-19 condition (NHLC) and posthospitalized participants with post-COVID-19 condition (PHC) showed hyperpolarized pulmonary xenon 129 MRI and red blood cell-to-tissue plasma abnormalities, with NHLC participants demonstrating lower gas transfer than PHC participants despite having normal CT findings. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Parraga and Matheson in this issue.

Weight loss during ambulatory tube weaning: don't put the feeds back up.

OBJECTIVE: To describe the prevalence of weight loss during tube weaning and its impact on wean duration and growth. SETTING: Tertiary feeding clinic, UK. PATIENTS: All children seen for weaning from long-term enteral feeding between 2008 and 2016. INTERVENTIONS: Outpatient withdrawal of enteral feeding. DESIGN: Case series of children being weaned from tube feeding, documenting clinical details, periods of weight loss and timing of feed changes, as well as height and weight at baseline and within 1 year after feed cessation. MAIN OUTCOME MEASURES: Amount and frequency of weight loss, wean duration, change in body mass index (BMI) and height SD z score. RESULTS: Weaning was attempted in 58 children, median age 2.7 years, and 90% had stopped feeds after median (range) 5.9 (1-40) months. Weight loss was seen in 51 (88%) children and was more common and severe in children with initially higher BMI. Time to feed cessation reduced by median 4.9 months between 2008-2011 and 2012-2016, while having feeds increased prolonged the wean duration, by median 13 months. After feed cessation, mean (95% CI) BMI had dropped by 0.84 (0.5 to 1.2) z scores, but neither change in BMI, nor the amount and frequency of weight loss, related to growth. CONCLUSIONS: Short-term weight loss is to be expected during tube weaning and is not associated with compromised growth. It is important to avoid overfeeding enterally fed children and not to increase feeds again in response to weight loss.

Hyperpolarized 129Xe MRI Abnormalities in Dyspneic Patients 3 Months after COVID-19 Pneumonia: Preliminary Results.

Background SARS-CoV-2 targets angiotensin-converting enzyme 2-expressing cells in the respiratory tract. There are reports of breathlessness in patients many months after infection. Purpose To determine whether hyperpolarized xenon 129 MRI (XeMRI) imaging could be used to identify the possible cause of breathlessness in patients at 3 months after hospital discharge following COVID-19 infection. Materials and Methods This prospective study was undertaken between August and December of 2020, with patients and healthy control volunteers being enrolled. All patients underwent lung function tests; ventilation and dissolved-phase XeMRI, with the mean red blood cell (RBC) to tissue or plasma (TP) ratio being calculated; and a low-dose chest CT, with scans being scored for the degree of abnormalities after COVID-19. Healthy control volunteers underwent XeMRI. The intraclass correlation coefficient was calculated for volunteer and patient scans to assess repeatability. A Wilcoxon rank sum test and Cohen effect size calculation were performed to assess differences in the RBC/TP ratio between patients and control volunteers. Results Nine patients (mean age, 57 years ± 7 [standard deviation]; six male patients) and five volunteers (mean age, 29 years ± 3; five female volunteers) were enrolled. The mean time from hospital discharge for patients was 169 days (range, 116-254 days). There was a difference in the RBC/TP ratio between patients and control volunteers (0.3 ± 0.1 vs 0.5 ± 0.1, respectively; P = .001; effect size, 1.36). There was significant difference between the RBC and gas phase spectral full width at half maximum between volunteers and patients (median ± range, 567 ± 1 vs 507 ± 81 [P = .002] and 104 ± 2 vs 122 ± 17 [P = .004], respectively). Results were reproducible, with intraclass correlation coefficients of 0.82 and 0.88 being demonstrated for patients and volunteers, respectively. Participants had normal or nearly normal CT scans (mean, seven of 25; range, zero of 25 to 10 of 25). Conclusion Hyperpolarized xenon 129 MRI results showed alveolar capillary diffusion limitation in all nine patients after COVID-19 pneumonia, despite normal or nearly normal results at CT. © RSNA, 2021 See also the editorial by Dietrich in this issue.

Multi-Modal Characterization of Monocytes in Idiopathic Pulmonary Fibrosis Reveals a Primed Type I Interferon Immune Phenotype.

Idiopathic pulmonary fibrosis (IPF) is the most severe form of chronic lung fibrosis. Circulating monocytes have been implicated in immune pathology in IPF but their phenotype is unknown. In this work, we determined the immune phenotype of monocytes in IPF using multi-colour flow cytometry, RNA sequencing and corresponding serum factors, and mapped the main findings to amount of lung fibrosis and single cell transcriptomic landscape of myeloid cells in IPF lungs. We show that monocytes from IPF patients displayed increased expression of CD64 (FcγR1) which correlated with amount of lung fibrosis, and an amplified type I IFN response ex vivo. These were accompanied by markedly raised CSF-1 levels, IL-6, and CCL-2 in serum of IPF patients. Interrogation of single cell transcriptomic data from human IPF lungs revealed increased proportion of CD64hi monocytes and "transitional macrophages" with higher expression of CCL-2 and type I IFN genes. Our study shows that monocytes in IPF patients are phenotypically distinct from age-matched controls, with a primed type I IFN pathway that may contribute to driving chronic inflammation and fibrosis. These findings strengthen the potential role of monocytes in the pathogenesis of IPF.

Successful awake proning is associated with improved clinical outcomes in patients with COVID-19: single-centre high-dependency unit experience.

The SARS-CoV-2 can lead to severe illness with COVID-19. Outcomes of patients requiring mechanical ventilation are poor. Awake proning in COVID-19 improves oxygenation, but on data clinical outcomes is limited. This single-centre retrospective study aimed to assess whether successful awake proning of patients with COVID-19, requiring respiratory support (continuous positive airways pressure (CPAP) or high-flow nasal oxygen (HFNO)) on a respiratory high-dependency unit (HDU), is associated with improved outcomes. HDU care included awake proning by respiratory physiotherapists. Of 565 patients admitted with COVID-19, 71 (12.6%) were managed on the respiratory HDU, with 48 of these (67.6%) requiring respiratory support. Patients managed with CPAP alone 22/48 (45.8%) were significantly less likely to die than patients who required transfer onto HFNO 26/48 (54.2%): CPAP mortality 36.4%; HFNO mortality 69.2%, (p=0.023); however, multivariate analysis demonstrated that increasing age and the inability to awake prone were the only independent predictors of COVID-19 mortality. The mortality of patients with COVID-19 requiring respiratory support is considerable. Data from our cohort managed on HDU show that CPAP and awake proning are possible in a selected population of COVID-19, and may be useful. Further prospective studies are required.

Readily accessible CT scoring method to quantify fibrosis in IPF.

INTRODUCTION: There is currently no readily accessible measure to specifically quantify the amount of fibrosis in idiopathic pulmonary fibrosis (IPF). Such a measure could isolate contribution of fibrosis from other comorbidities to lung function abnormality and deterioration of disease, and potentially help determine if there has been response to antifibrotic treatment. METHODS: In a pilot study of 39 IPF patients, we used a CT-based visual scoring method to examine the correlation between the sum of all fibrotic features (all traction bronchiectasis, ground glass with traction bronchiectasis, honeycombing and reticulation; referred to as Total Fibrosis Score, TFS) or the individual fibrotic features, with lung function, Composite Physiologic Index (CPI) and time to death in the 5 years following CT measurement. RESULTS: TFS measurements were highly reproducible (r=0.982; p<0.001) and correlated significantly with TLCO, FVC and CPI. Traction bronchiectasis score was superior to others in its correlation to lung function and CPI, and as good as TFS. TFS and traction bronchiectasis score were also the best correlates (individually) to time to death (r=0.60 for both, and p=0.002 and p=0.004, respectively). CONCLUSION: We suggest that TFS and our 6-slices method of quantifying traction bronchiectasis on CT scans could be readily accessible and simple methods of quantifying lung fibrosis in IPF. These scores could assist in determining if clinical deterioration is due to worsening fibrosis, for correlation of research findings to amount of lung fibrosis, and to stratify patients for established drug treatment and clinical trials. Our findings also provide a basis for larger studies to validate these findings and determine if the scores could measure change in fibrosis.

Perceived Caretaker Malevolence During Childhood Reported by Borderline Patients and Personality-Disordered Comparison Subjects: Description and Prediction.

This study has two purposes. The first is to assess the rates of childhood malevolence by caretakers reported by a well-defined sample of inpatients with borderline personality disorder (BPD) and comparison subjects with other personality disorders. The second purpose is to determine the relationship between reported malevolence of caretakers and possible risk factors for this experience. Two reliable interviews were administered to 290 borderline inpatients and 72 personality-disordered comparison subjects to address these aims. Malevolence was reported by a significantly higher percentage of borderline patients than comparison subjects (58% vs. 33%). In multivariate analyses, severity of other forms of abuse, severity of neglect, and a family history of a dramatic cluster personality disorder were found to significantly predict perceived malevolence. Taken together, the results of this study suggest that experiencing malevolence is common and distinguishing for BPD, and that the risk factors for reported childhood malevolence are multifactorial in nature.

Malnutrition risk of older people across district health board community, hospital and residential care settings in New Zealand.

OBJECTIVE: To determine the prevalence of malnutrition risk in older people across three settings. METHODS: Older people living in the community or newly admitted to hospital or residential care were assessed for malnutrition risk using the validated Mini-Nutritional Assessment - Short Form and dysphagia risk using the Eating Assessment Tool-10. Demographic, physical and health data were collected. RESULTS: Of 167 participants, 23% were malnourished and 35% were at high risk of malnutrition. Those recently admitted to residential care versus a hospital or living in the community had a higher prevalence of malnourishment (47% vs 23% and 2%) (P < 0.001). Risk of dysphagia differed with settings (P < 0.001) with highest risk in residential care. Hospitalised and residential care participants were significantly more likely to have ≥4 comorbidities, take ≥5 medications and have below normal cognition compared to community participants. CONCLUSION: Choice of nutrition intervention is setting dependent.

Therapeutic advances in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive accumulation of scar tissue in the lung and is associated with a median life expectancy of 2-4 years. Until recently, treatment options were limited, focusing on ineffective anti-inflammatory therapy, palliation, transplant or trial recruitment. Significant recent advances in the field have led to two novel anti-fibrotic agents, pirfenidone and nintedanib, which have been shown to significantly slow disease progression in IPF. This article outlines the approach to management of IPF, the role of specialist centres and specialist interstitial lung disease multidisciplinary review, and explores both the trial evidence and practical considerations in the use of these anti-fibrotic agents.

Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study.

BACKGROUND: Information on demographics and survival of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this study was to describe the incidence, characteristics, causes of death and survival rates of RRT for ESRD due to MM or LCDD in the ERA-EDTA Registry. METHODS: Thirteen national registries providing data on patients who started RRT from 1986-2005 to the ERA-EDTA Registry participated. Incidence per million population (pmp) of RRT for ESRD due to MM or LCDD and other causes (non-MM) was observed overtime. Patient survival on RRT was examined, unadjusted and adjusted for age and gender. RESULTS: Of the 159 637 patients on RRT, 2453 (1.54%) had MM or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and gender, increased from 0.70 pmp in 1986-1990 to 2.52 pmp in 2001-2005. MM and LCDD patients compared to non-MM patients were older and a higher percentage was on haemodialysis at day 91 after the start of RRT. The most common causes of death in MM and LCDD patients were malignancy (36.1%), cardiovascular causes (17.2%) and infection (14.7%). MM and LCDD patients had a 2.77 (95% CI, 2.65-2.90) higher risk of death compared to non-MM patients. The unadjusted median survival on RRT was 0.91 years in MM and LCDD patients and 4.46 years in non-MM patients. During follow-up, 35 patients were transplanted and their mean survival was 9.6 years. CONCLUSION: The incidence of RRT for ESRD due to MM or LCDD has increased over the past 20 years in Europe. The median patient survival on RRT for MM and LCDD patients was 0.91 years, compared to 4.46 years for non-MM patients. These results suggest that dialysis, and in selected cases even transplantation, should be offered to MM and LCDD patients.