Colony stimulating factor-1 receptor drives glomerular parietal epithelial cell activation in focal segmental glomerulosclerosis.

Parietal epithelial cells (PECs) are kidney progenitor cells with similarities to a bone marrow stem cell niche. In focal segmental glomerulosclerosis (FSGS) PECs become activated and contribute to extracellular matrix deposition. Colony stimulating factor-1 (CSF-1), a hematopoietic growth factor, acts via its specific receptor, CSF-1R, and has been implicated in several glomerular diseases, although its role on PEC activation is unknown. Here, we found that CSF-1R was upregulated in PECs and podocytes in biopsies from patients with FSGS. Through in vitro studies, PECs were found to constitutively express CSF-1R. Incubation with CSF-1 induced CSF-1R upregulation and significant transcriptional regulation of genes involved in pathways associated with PEC activation. Specifically, CSF-1/CSF-1R activated the ERK1/2 signaling pathway and upregulated CD44 in PECs, while both ERK and CSF-1R inhibitors reduced CD44 expression. Functional studies showed that CSF-1 induced PEC proliferation and migration, while reducing the differentiation of PECs into podocytes. These results were validated in the Adriamycin-induced FSGS experimental mouse model. Importantly, treatment with either the CSF-1R-specific inhibitor GW2580 or Ki20227 provided a robust therapeutic effect. Thus, we provide evidence of the role of the CSF-1/CSF-1R pathway in PEC activation in FSGS, paving the way for future clinical studies investigating the therapeutic effect of CSF-1R inhibitors on patients with FSGS.

Therapeutic approach to dysphagia in post-COVID patients in a rehabilitation unit: a descriptive longitudinal study.

BACKGROUND: A high rate of hospitalized patients for COVID-19 had dysphagia, frequently underdiagnosed, and not treated, inducing a prolonged dysphagia with protracted recovery. Specific treatments and protocols have not been well described yet. AIM: Given the potential benefits of respiratory muscle training (IEMT) and neuromuscular stimulation (NMES) in dysphagia treatment, this study aimed to assess the feasibility of the protocol used for treating dysphagia in patients who experienced prolonged hospitalization for COVID-19. DESIGN: Observational, descriptive, prospective study. SETTING: Department of Physical Medicine and Rehabilitation of a tertiary University hospital. POPULATION: Fifty-eight COVID-19 patients were admitted for intensive rehabilitation (March 2020 to October 2021) were prospectively studied. METHODS: Dysphagia was diagnosed using videofluoroscopy and treated with a 3-week protocol adapted from neuromuscular stimulation (NMES) in a motor threshold and inspiratory/expiratory muscle strength training (IEMST), five sets of five repetitions three times daily for 3 weeks. Feasibility was assessed with adherence, outcomes achieved, and occurrence of adverse/unexpected events. Respiratory function (peak cough flow, maximal inspiratory/expiratory pressures) and swallow function (Penetration-Aspiration Scale and Bolus Residue Scale measured by videofluoroscopy) were recorded descriptive statistics, Student's t test for numerical data, and Wilcoxon Test for ordinal variables were applied. SPPSS vs28 and STATA version 15.1 (StataCorp, College Station, TX, USA) were used for statistical analysis. P values 0.05 were considered significant. RESULTS: Dysphagia was highly prevalent in severe COVID-19 patients (86.6%); all respiratory and swallow parameters improved after a 3-week intervention and 12 of 18 patients dependent on tube feeding resumed a normal diet (66.7%; McNemar P=0.03), and 84.09% attended a no restriction diet at discharge. Adherence to treatment was 85%. No significant adverse events were detected. CONCLUSIONS: We conclude that a structured swallowing-exercise training intervention based on IEMT and NMES is feasible and safe in prolonged hospitalization post-COVID patients. CLINICAL REHABILITATION IMPACT: To describe rehabilitation protocols used to treat dysphagia in post-COVID patients will help us to optimize the available techniques in each center and to induce a faster recovery avoiding potential complications.

Sound-based cough peak flow estimation in patients with neuromuscular disorders.

INTRODUCTION/AIMS: Cough impairment is common in individuals with neuromuscular disorders and is associated with respiratory infections and shorter survival. Cough strength is assessed by measuring cough peak flow (CPF) using a flow meter, but this method requires a complex device setup and trained staff. The aim of the study is to evaluate the reliability of a smartphone app to estimate CPF based on cough sounds in a cohort of individuals with neuromuscular disorders. METHODS: Individuals with neuromuscular disorders underwent CPF measurement with a flow meter and a smartphone app. A CPF <270 L/min was considered abnormal. RESULTS: Of the 50 patients studied, 26 had amyotrophic lateral sclerosis (52%), 15 had hereditary myopathies (30%), and 9 had myasthenia gravis (18%). The intraclass correlation coefficient (ICC) between the CPF measured with a flow meter and CPF estimated with cough sounds was 0.774 (p < .001) even if the patients had orofacial weakness (ICC = 0.806, p < .001). The smartphone app had 94.4% sensitivity and 100% specificity to detect patients with CPF of less than 270 L/min. DISCUSSION: Our findings suggest that sounds measured with a smartphone app provide a reliable estimate of CPF in patients with neuromuscular disorders, even in the presence of with orofacial weakness. This may be a convenient way to monitor respiratory involvement in patients with neuromuscular disorders, but larger studies of more diverse patient cohorts are needed.

Accuracy of the volume-viscosity swallow test for clinical screening of dysphagia in post COVID-19 patients.

BACKGROUND & AIMS: Up to 30% of patients hospitalized for COVID-19 had oropharyngeal dysphagia, particularly those in the ICU. Many cases remained underdiagnosed due to difficulties in conducting instrumental evaluations during the pandemic. Consequently, screening tests were mandatory during this period. OBJECTIVES: To evaluate the accuracy of the volume-viscosity swallow test (V-VST), compared to gold standard videofluoroscopy, for screening dysphagia in a post-COVID cohort of patients. MATERIAL AND METHODS: We conducted a prospective single-center study involving 58 post-COVID adult patients with no previous history of dysphagia. Blinded raters performed the index V-VST upon admission and a standardized videofluoroscopy (VFSS, the reference test) within 72 h of patient intake. Oropharyngeal residue was considered a sign of impaired efficacy. Cough, decreased oxygen saturation, and voice changes were noted as signs of impaired safety. Accuracy, sensitivity, specificity, positive, and negative predictive values, and likelihood ratios were calculated for V-VST results and compared to the gold standard. RESULTS: Patients (aged 59.98 (SD11.53) years) spent a mean of 46.98 (SD 28.43) days in ICU, 33.76 (SD34.88) days with tracheostomy, and 19.46 (SD13.26) days in the NeuroRehabilitation Unit. The V-VST showed the following properties, compared to VFSS: sensitivity 55.6%, specificity 62.9%, positive predictive value 44.5%, negative predictive value 37.1%, and accuracy 61.5%. CONCLUSION: The V-VST showed mild accuracy, sensitivity, and specificity, compared to VFSS. Therefore, it should not be used as a stand-alone test for screening dysphagia in patients with a history of COVID.

The effect of a motor relearning on balance and postural control in patients after stroke: An open-label randomized controlled trial.

INTRODUCTION: Balance and postural control impairments are common in stroke patients, increasing fall risk and limiting their daily and social activities. Current research lacks comprehensive studies evaluating the efficacy and long-term effects of task-specific training on balance and postural control among stroke patients, especially when considering biomechanical and posturographic assessments. PATIENTS AND METHODS: A randomized controlled trial included 63 subacute stroke patients recruited from the outpatient rehabilitation department. Participants were randomly assigned to the MRP group (n=32), receiving task-specific training based on MRP, or the CPT group (n=31), receiving conventional physical therapy. Both groups completed an 8-week intervention (3 sessions/week; 1 h./session). Balance and postural control were assessed at baseline, post-intervention, and 3-month follow-up using the Berg Balance Scale (BBS) and posturography. RESULTS: The MRP group exhibited significantly larger improvements than the CPT group in both BBS scores (p=0.001, d=2.98, 95% CI [2.25, 3.70]) and Balance Index scores (p=0.001, d=2.83, 95% CI [2.12, 3.53]) after the intervention. These improvements were sustained at 3-month follow-up. DISCUSSION: The findings suggest that task-specific training based on MRP is more effective than CPT for improving balance and postural control. The MRP intervention may enhance the motor learning and neural plasticity of the patients, leading to better functional outcomes. However, the study's open-label design represents a limitation, and further research with adequate blinding is needed. CONCLUSION: Task-specific training based on MRP was superior to CPT for improving balance and postural control in subacute stroke patients. Participants undergoing MRP exhibited significant and clinically relevant improvements that were sustained at follow-up.

Iron accumulation drives fibrosis, senescence and the senescence-associated secretory phenotype.

Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). Here, we report that cellular senescence, and multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries are efficient in triggering iron accumulation, which in turn can cause senescence and promote fibrosis. Notably, we find that senescent cells persistently accumulate iron, even when the surge of extracellular iron has subdued. Indeed, under normal conditions of extracellular iron, cells exposed to different types of senescence-inducing insults accumulate abundant ferritin-bound iron, mostly within lysosomes, and present high levels of labile iron, which fuels the generation of reactive oxygen species and the SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging might allow non-invasive assessment of fibrotic burden in the kidneys of mice and in patients with renal fibrosis. Our findings suggest that iron accumulation plays a central role in senescence and fibrosis, even when the initiating events may be independent of iron, and identify iron metabolism as a potential therapeutic target for senescence-associated diseases.

Ultrasonographic and manometric study of the tongue as biomarkers of dysphagia in patients with amyotrophic lateral sclerosis.

BACKGROUND: The possibility of having methods to assess dysphagia in amyotrophic lateral sclerosis (ALS) patients in a minimally invasive manner could facilitate follow-up and allow performing of therapeutic interventions at earlier stages of the disease. The aim of the study was to analyze the role of tongue strength and thickness in ALS patients and their correlation with dysphagia and bulbar function. METHODS: A sample of outpatients with ALS was evaluated for demographic and clinical features. Tongue thickness and strength have been measured for each patient, and quantitative and qualitative data of the videofluoroscopy swallow study have been analyzed. RESULTS: Of the 38 ALS patients studied, 47.4% were women, and 26.3% had bulbar onset. The median time between symptom onset and the study was 24 months (IQR 11.5-48), and 55.3% of the patients were carriers of non-invasive mechanical ventilation. Tongue strength identified patients with impaired oral and pharyngeal transit and those with bolus residue scale (BRS) > 1 or penetration-aspiration scale (PAS) ≥ 3. In contrast, tongue thickness is only associated with impaired oral transit. Finally, anterior tongue strength ≤ 34 kPa and posterior tongue strength ≤ 34.5 kPa detected ALS penetrators/aspirators (PAS ≥ 3) and patients with ALS with post-swallow residue (BRS > 1). CONCLUSIONS: Our results suggest that measures that assess the functionality (strength) of the tongue are more valuable than morphological measurements (thickness) for the follow-up of patients with ALS. Alterations of the anterior and posterior lingual strength correlate with the presence of bronchoaspiration and post-swallowing residue (BRS > 1).

Dysphagia in hospitalized patients: Prevalence, related factors and impact on aspiration pneumonia and mortality.

BACKGROUND: Oropharyngeal dysphagia can be highly concerning in hospitalized patients, increasing morbidity and mortality, making its early identification essential. We aimed to characterize dysphagia and its association with aspiration pneumonia and mortality in a tertiary hospital in Barcelona, Spain. METHODS: Using data from all hospital discharges during the period 2018-2021, we identified the characteristics of patients with dysphagia and their distribution among hospital departments through the minimum data set, which codifies patients' diagnoses according to the International Classification of Diseases 10th Revision (ICD-10). We used logistic regression models to assess the association between dysphagia, aspiration pneumonia and mortality. RESULTS: Dysphagia was present in 2.4% of all hospital discharges and was more frequent in older patients and in men. The diagnoses most frequently associated with dysphagia were aspiration pneumonia (48.2%) and stroke (14%). Higher prevalence of dysphagia was found in the acute geriatric unit (10.3%), neurology (7.6%) and internal medicine (7.5%) wards. Dysphagia was associated with aspiration pneumonia, aOR = 8.04 (95%CI, 6.31-10.25), and independently increased the odds of death among hospitalized patients, aOR = 1.43 (95%CI, 1.19-1.73). CONCLUSIONS: We conclude that dysphagia is a prevalent and transversal condition, increasing the risk of mortality in all patients, and efforts should be intensified to increase its early detection and correct management.

Citizen-science reveals changes in the oral microbiome in Spain through age and lifestyle factors.

The relevance of the human oral microbiome to our understanding of human health has grown in recent years as microbiome studies continue to develop. Given the links of the oral cavity with the digestive, respiratory and circulatory systems, the composition of the oral microbiome is relevant beyond just oral health, impacting systemic processes across the body. However, we still have a very limited understanding about intrinsic and extrinsic factors that shape the composition of the healthy oral microbiome. Here, we followed a citizen-science approach to assess the relative impact on the oral microbiome of selected biological, social, and lifestyle factors in 1648 Spanish individuals. We found that the oral microbiome changes across age, with middle ages showing a more homogeneous composition, and older ages showing more diverse microbiomes with increased representation of typically low abundance taxa. By measuring differences within and between groups of individuals sharing a given parameter, we were able to assess the relative impact of different factors in driving specific microbial compositions. Chronic health disorders present in the analyzed population were the most impactful factors, followed by smoking and the presence of yeasts in the oral cavity. Finally, we corroborate findings in the literature that relatives tend to have more similar oral microbiomes, and show for the first time a similar effect for classmates. Multiple intrinsic and extrinsic factors jointly shape the oral microbiome. Comparative analysis of metabarcoding data from a large sample set allows us to disentangle the individual effects.

Epigenetic Modulation of Gremlin-1/NOTCH Pathway in Experimental Crescentic Immune-Mediated Glomerulonephritis.

Crescentic glomerulonephritis is a devastating autoimmune disease that without early and properly treatment may rapidly progress to end-stage renal disease and death. Current immunosuppressive treatment provides limited efficacy and an important burden of adverse events. Epigenetic drugs are a source of novel therapeutic tools. Among them, bromodomain and extraterminal domain (BET) inhibitors (iBETs) block the interaction between bromodomains and acetylated proteins, including histones and transcription factors. iBETs have demonstrated protective effects on malignancy, inflammatory disorders and experimental kidney disease. Recently, Gremlin-1 was proposed as a urinary biomarker of disease progression in human anti-neutrophil cytoplasmic antibody (ANCA)-associated crescentic glomerulonephritis. We have now evaluated whether iBETs could regulate Gremlin-1 in experimental anti-glomerular basement membrane nephritis induced by nephrotoxic serum (NTS) in mice, a model resembling human crescentic glomerulonephritis. In NTS-injected mice, the iBET JQ1 inhibited renal Gremlin-1 overexpression and diminished glomerular damage, restoring podocyte numbers. Chromatin immunoprecipitation assay demonstrated BRD4 enrichment of the Grem-1 gene promoter in injured kidneys, consistent with Gremlin-1 epigenetic regulation. Moreover, JQ1 blocked BRD4 binding and inhibited Grem-1 gene transcription. The beneficial effect of iBETs was also mediated by modulation of NOTCH pathway. JQ1 inhibited the gene expression of the NOTCH effectors Hes-1 and Hey-1 in NTS-injured kidneys. Our results further support the role for epigenetic drugs, such as iBETs, in the treatment of rapidly progressive crescentic glomerulonephritis.

Mitochondrial Transplantation Enhances Phagocytic Function and Decreases Lipid Accumulation in Foam Cell Macrophages.

Macrophages have mechanisms for eliminating cholesterol from cells. If excess cholesterol is not eliminated from the macrophages, then transformation into a foam cell may occur. Foam cells are a hallmark of the atherosclerotic lesions that contribute to the development and rupture of atherosclerotic plaques. Several in vitro and in vivo studies have shown changes in the macrophage phenotype and improved phagocytosis after the acquisition of functional mitochondria. However, the effect of mitochondrial transplantation on promoting phagocytosis and phenotypic changes in lipid-loaded macrophages leading to foam cells has not been studied. We aimed to prove that the transplantation of healthy mitochondria to highly cholesterol-loaded macrophages induces macrophage phagocytosis and reduces the macrophage shift towards foam cells. For this purpose, using a murine macrophage cell line, RAW264.7, we determined if mitochondria transplantation to 7-ketocholesterol (7-KC)-loaded macrophages reduced lipid accumulation and modified their phagocytic function. We evidenced that mitochondrial transplantation to 7-KC-loaded macrophages reestablished phagocytosis and reduced lipid content. In addition, CPT1a expression and anti-inflammatory cytokines were restored after mitochondrial transplantation. We have developed a potential therapeutic approach to restore foam cell functionality.

Molecular Mechanisms of Kidney Injury and Repair.

Chronic kidney disease (CKD) will become the fifth global cause of death by 2040, thus emphasizing the need to better understand the molecular mechanisms of damage and regeneration in the kidney. CKD predisposes to acute kidney injury (AKI) which, in turn, promotes CKD progression. This implies that CKD or the AKI-to-CKD transition are associated with dysfunctional kidney repair mechanisms. Current therapeutic options slow CKD progression but fail to treat or accelerate recovery from AKI and are unable to promote kidney regeneration. Unraveling the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of this process, may provide novel biomarkers and therapeutic tools. We now review the contribution of different molecular and cellular events to the AKI-to-CKD transition, focusing on the role of macrophages in kidney injury, the different forms of regulated cell death and necroinflammation, cellular senescence and the senescence-associated secretory phenotype (SAPS), polyploidization, and podocyte injury and activation of parietal epithelial cells. Next, we discuss key contributors to repair of kidney injury and opportunities for their therapeutic manipulation, with a focus on resident renal progenitor cells, stem cells and their reparative secretome, certain macrophage subphenotypes within the M2 phenotype and senescent cell clearance.

Intensive rehabilitation programme for patients with subacute stroke in an inpatient rehabilitation facility: describing a protocol of a prospective cohort study.

INTRODUCTION: Rehabilitation is recognised as a cornerstone of multidisciplinary stroke care. Intensity of therapy is related to functional recovery although there is high variability on the amount of time and techniques applied in therapy sessions. There is a need to better describe stroke rehabilitation protocols to develop a better understanding of current practice increasing the internal validity and generalisation of clinical trial results. The aim of this study is to describe an intensive rehabilitation programme for patients with stroke in an inpatient rehabilitation facility, measuring the amount and type of therapies (physical, occupational and speech therapy) provided and reporting functional outcomes. METHODS AND ANALYSIS: This will be a prospective observational cohort study of patients with subacute stroke admitted to our inpatient rehabilitation facility during 2 years. A therapy recording tool was developed in order to describe the rehabilitation interventions performed in our unit. This tool was designed using the Delphi method, literature search and collaboration with senior clinicians. Therapists will record the time spent on different activities available in our unit during specific therapy sessions. Afterwards, the total time spent in each activity, and the total rehabilitation time for all activities, will be averaged for all patients. Outcome variables were divided into three different domains: body structure and function outcomes, activity outcomes and participation outcomes and will be assessed at baseline (admission at the rehabilitation unit), at discharge from the rehabilitation unit and at 3 and 6 months after stroke. ETHICS AND DISSEMINATION: This study was approved by the Medical Research Committee at Hospital del Mar Research Institute (Project ID: 34/C/2017). The results of this study will be presented at national and international congress and submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04191109.

Chronic Kidney Allograft Disease: New Concepts and Opportunities.

Chronic kidney disease (CKD) is increasing in most countries and kidney transplantation is the best option for those patients requiring renal replacement therapy. Therefore, there is a significant number of patients living with a functioning kidney allograft. However, progressive kidney allograft functional deterioration remains unchanged despite of major advances in the field. After the first post-transplant year, it has been estimated that this chronic allograft damage may cause a 5% graft loss per year. Most studies focused on mechanisms of kidney graft damage, especially on ischemia-reperfusion injury, alloimmunity, nephrotoxicity, infection and disease recurrence. Thus, therapeutic interventions focus on those modifiable factors associated with chronic kidney allograft disease (CKaD). There are strategies to reduce ischemia-reperfusion injury, to improve the immunologic risk stratification and monitoring, to reduce calcineurin-inhibitor exposure and to identify recurrence of primary renal disease early. On the other hand, control of risk factors for chronic disease progression are particularly relevant as kidney transplantation is inherently associated with renal mass reduction. However, despite progress in pathophysiology and interventions, clinical advances in terms of long-term kidney allograft survival have been subtle. New approaches are needed and probably a holistic view can help. Chronic kidney allograft deterioration is probably the consequence of damage from various etiologies but can be attenuated by kidney repair mechanisms. Thus, besides immunological and other mechanisms of damage, the intrinsic repair kidney graft capacity should be considered to generate new hypothesis and potential therapeutic targets. In this review, the critical risk factors that define CKaD will be discussed but also how the renal mechanisms of regeneration could contribute to a change chronic kidney allograft disease paradigm.

Infusion of Phagocytic Macrophages Overexpressing CPT1a Ameliorates Kidney Fibrosis in the UUO Model.

Phagocytosis is an inherent function of tissue macrophages for the removal of apoptotic cells and cellular debris during acute and chronic injury; however, the dynamics of this event during fibrosis development is unknown. We aim to prove that during the development of kidney fibrosis in the unilateral ureteral obstruction (UUO) model, there are some populations of macrophage with a reduced ability to phagocytose, and whether the infusion of a population of phagocytic macrophages could reduce fibrosis in the murine model UUO. For this purpose, we have identified the macrophage populations during the development of fibrosis and have characterized their phagocytic ability and their expression of CPT1a. Furthermore, we have evaluated the therapeutic effect of macrophages overexpressing CPT1a with high phagocytic skills. We evidenced that the macrophage population which exhibits high phagocytic ability (F4/80low-CD11b) in fibrotic animals decreases during the progression of fibrosis while the macrophage population with lower phagocytic ability (F4/80high-CD11b) in fibrotic conditions, conversely, increases and CPT1a macrophage cell therapy with a strengthening phagocytic ability is associated with a therapeutic effect on kidney fibrosis. We have developed a therapeutic approach to reduce fibrosis in the UUO model by enrichment of the kidney resident macrophage population with a higher proportion of exogenous phagocytic macrophages overexpressing CPT1a.

Citizen-science based study of the oral microbiome in Cystic fibrosis and matched controls reveals major differences in diversity and abundance of bacterial and fungal species.

Introduction: Cystic fibrosis (CF) is an autosomal genetic disease, associated with the production of excessively thick mucosa and with life-threatening chronic lung infections. The microbiota of the oral cavity can act as a reservoir or as a barrier for infectious microorganisms that can colonize the lungs. However, the specific composition of the oral microbiome in CF is poorly understood.Methods: In collaboration with CF associations in Spain, we collected oral rinse samples from 31 CF persons (age range 7-47) and matched controls, and then performed 16S rRNA metabarcoding and high-throughput sequencing, combined with culture and proteomics-based identification of fungi to survey the bacterial and fungal oral microbiome.Results: We found that CF is associated with less diverse oral microbiomes, which were characterized by higher prevalence of Candida albicans and differential abundances of a number of bacterial taxa that have implications in both the connection to lung infections in CF, as well as potential oral health concerns, particularly periodontitis and dental caries.Conclusion: Overall, our study provides a first global snapshot of the oral microbiome in CF. Future studies are required to establish the relationships between the composition of the oral and lung microbiomes in CF.

Malnutrition According to GLIM Criteria Is Associated with Mortality and Hospitalizations in Rehabilitation Patients with Stable Chronic Obstructive Pulmonary Disease.

Malnutrition has a negative impact on patients with chronic pulmonary obstructive disease (COPD). The purpose of this study was to assess the prevalence of malnutrition, defined by the Global Leadership Initiative for Malnutrition (GLIM), in stable COPD patients referred to pulmonary rehabilitation, and to explore potential associations of malnutrition according to GLIM, and its components, with increased risk of mortality and hospitalizations in 2 years. In a post-hoc analysis of a prospective cohort of 200 rehabilitation patients with stable COPD, main outcome variables were hospital admissions, length of stay, and mortality during a 2-year follow-up. Covariates were malnutrition according to GLIM and its phenotypic criteria: unintentional weight loss, low body mass index (BMI), and low fat-free mass (FFM). Univariate and multivariate analysis were performed using logistic and proportional hazard Cox regression. Malnutrition according to GLIM showed 45% prevalence and was associated with increased mortality risk. Low age-related BMI and FFM were independently associated with mortality, which persisted after adjustment for age and lung function. Malnutrition and low BMI were also associated with increased risk of hospitalization. Malnutrition according to GLIM criteria was highly prevalent in rehabilitation patients with COPD and was associated with nearly 3 times greater mortality and hospitalization risk.

Is EAT-10 Useful to Assess Swallowing during the Chemo-Radiotherapy Phase in Patients with Head and Neck Cancer? A Pilot Study.

OBJECTIVE/HYPOTHESIS: The 10-item Eating-Assessment Tool (EAT-10) is a dysphagia screening test. In HNC patients, screening and diagnosis of dysphagia are not well-established. To determine the metrological properties of the EAT-10 compared with videofluoroscopy in non-surgical HNC-patients and to assess the relationship between EAT-10 scores and patients' self-reported symptoms. STUDY DESIGN: Prospective cohort study. METHODS: Forty-six HNC-patients recently diagnosed and referred to chemoradiotherapy (CRT). Main outcome was evidence of dysphagia according to EAT-10 score, self-perception on a Visual Analog Scale (VAS) of impaired swallowing, severity on the Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale (FOIS). Patients were assessed at baseline, before-CRT, after-CRT, and at 3-month follow-up. RESULTS: A strong baseline correlation between EAT-10, VAS, and FOIS was observed. All 3 values decreased in weeks 6 to 9 after CRT initiation; a poor correlation of EAT-10 with VAS was observed at 3-month follow-up. A receiver operating characteristic curve determined new cut-off points (sensitivity/specificity) for safe swallowing: baseline 3 (86%, 77%); post-CRT, 15 (62.5%, 80%); and 3-month follow-up, 4 (83%, 75%). CONCLUSIONS: New safe-swallow EAT-10-points are suggested for this population during screening and the oncological follow-up. A poor correlation between EAT10-score and patient self-reported symptoms was observed at the end-RT and at 3-month follow-up, highlighting the need for an objective evaluation instrument.

Cerebral infarct site and affected vascular territory as factors in breathing weakness in patients with subacute stroke.

OBJECTIVE: A better understanding of factors influencing breathing weakness in stroke survivors would help in planning rehabilitation therapies. The main objective of this study was to determine whether the location of cerebral infarct is associated with breathing weakness in patients with subacute stroke. DESIGN: Cross-sectional analysis of a prospective cohort. PATIENTS: Consecutive patients admitted to a neurology rehabilitation unit with first-time ischaemic stroke (n?=?170). METHODS: Breathing weakness was defined as >?70% reduction in maximal inspiratory and expiratory pressures (PImax and PEmax, respectively) compared with reference values. Computed tomography and magnetic resonance imaging were used to locate stroke lesions, which were classified as cortical, subcortical, cortico-subcortical, brainstem, or cerebellum. The affected cerebrovascular territory was identified to classify stroke subtype. The association between maximal respiratory pressure and affected brain area was studied using median regression analysis. RESULTS: Breathing weakness was detected in 151 (88.8%) patients. Those with cortical and cortico-subcortical stroke location had the lowest PImax and PEmax values (median 33 cmH2O). This value differed significantly from maximal respiratory pressures of patients with strokes located in the brainstem and the cerebellum, with PImax median differences (?) of 16 cmH2O (95% confidence interval (95% CI) 4.127.9) and 27 cmH2O (95% CI 7.846.2), respectively, and PEmax median differences of 27 cmH2O (95% CI 11.442.7) and 49 cmH2O (95% CI 23.774.3), respectively, both of which remained significant after adjustments. CONCLUSION: The prevalence of breathing weakness was very high in stroke patients admitted to a neurorehabilitation ward, being more severe in cortical or cortico-subcortical stroke.

Macrophage-Derived Iron-Bound Lipocalin-2 Correlates with Renal Recovery Markers Following Sepsis-Induced Kidney Damage.

During the course of sepsis in critically ill patients, kidney dysfunction and damage are among the first events of a complex scenario toward multi-organ failure and patient death. Acute kidney injury triggers the release of lipocalin-2 (Lcn-2), which is involved in both renal injury and recovery. Taking into account that Lcn-2 binds and transports iron with high affinity, we aimed at clarifying if Lcn-2 fulfills different biological functions according to its iron-loading status and its cellular source during sepsis-induced kidney failure. We assessed Lcn-2 levels both in serum and in the supernatant of short-term cultured renal macrophages (MΦ) as well as renal tubular epithelial cells (TEC) isolated from either Sham-operated or cecal ligation and puncture (CLP)-treated septic mice. Total kidney iron content was analyzed by Perls' staining, while Lcn-2-bound iron in the supernatants of short-term cultured cells was determined by atomic absorption spectroscopy. Lcn-2 protein in serum was rapidly up-regulated at 6 h after sepsis induction and subsequently increased up to 48 h. Lcn-2-levels in the supernatant of TEC peaked at 24 h and were low at 48 h with no change in its iron-loading. In contrast, in renal MΦ Lcn-2 was low at 24 h, but increased at 48 h, where it mainly appeared in its iron-bound form. Whereas TEC-secreted, iron-free Lcn-2 was associated with renal injury, increased MΦ-released iron-bound Lcn-2 was linked to renal recovery. Therefore, we hypothesized that both the cellular source of Lcn-2 as well as its iron-load crucially adds to its biological function during sepsis-induced renal injury.