Incremental peritoneal dialysis: a 10 year single-centre experience

INTRODUCTION: Incremental dialysis consists in prescribing a dialysis dose aimed towards maintaining total solute clearance (renal + dialysis) near the targets set by guidelines. Incremental peritoneal dialysis (incrPD) is defined as one or two dwell-times per day on CAPD, whereas standard peritoneal dialysis (stPD) consists in three-four dwell-times per day. PATIENTS AND METHODS: Single-centre cohort study. Enrollement period: January 2002-December 2007; end of follow up (FU): December 2012. INCLUSION CRITERIA: incident patients with FU ≥6 months, initial residual renal function (RRF) 3-10 ml/min/1.73 sqm BSA, renal indication for PD. RESULTS: Median incrPD duration was 17 months (I-III Q: 10; 30). There were no statistically significant differences between 29 patients on incrPD and 76 on stPD regarding: clinical, demographic and anthropometric characteristics at the beginning of treatment, adequacy indices, peritonitis-free survival (peritonitis incidence: 1/135 months-patients in incrPD vs. 1/52 months-patients in stPD) and patient survival. During the first 6 months, RRF remained stable in incrPD (6.20 ± 2.02 vs. 6.08 ± 1.47 ml/min/1.73 sqm BSA; p = 0.792) whereas it decreased in stPD (4.48 ± 2.12 vs. 5.61 ± 1.49; p < 0.001). Patient survival was affected negatively by ischemic cardiopathy (HR: 4.269; p < 0.001), peripheral and cerebral vascular disease (H2.842; p = 0.006) and cirrhosis (2.982; p = 0.032) and positively by urine output (0.392; p = 0.034). Hospitalization rates were significantly lower in incrPD (p = 0.021). Eight of 29 incrPD patients were transplanted before reaching full dose treatment. CONCLUSIONS: IncrPD is a safe modality to start PD; compared to stPD, it shows similar survival rates, significantly less hospitalization, a trend towards lower peritonitis incidence and slower reduction of renal function

Advances in the neurorehabilitation of severe disorder of consciousness

Introduction. The paper describes the evolution of knowledge concerning severe brain  injury which determines the Vegetative State/Unresponsive Wakefulness Syndrome. Background. The term Vegetative State was proposed by Jennet and Plum in 1972. Later  on, the Intensive Care Units progresses increased the survival of these patients and, contemporary, decreased their characteristic conditions of cachexia and severe dystonia. In  1994, the disease was conceived as a disconnection syndrome of the hemispheres from the  brainstem, mainly due to a temporary or permanent deficit of the functions of the white  matter. From 2005 on, the psychophysiological parameters relative to an emotional consciousness, albeit submerged, were described. Since then, it has been recognized that the  brain of these patients was not only to be considered living but also working.Conclusion. The latest studies that have greatly improved the knowledge of the physi-opathology of this particular state of consciousness. These new insights have led to the  formation of a European Union Task Force, which has proposed in 2009 to change the  name  from  a  Vegetative  State  to  Unresponsive  Wakefulness  Syndrome,  outlining  the  character of syndrome and not that of state, as forms of even late recovery in consciousness levels have been observed and described. 

Maintenance sunitinib or observation in metastatic pancreatic adenocarcinoma: a phase II randomised trial

Background: New strategies to prolong disease control warrant investigation in patients with metastatic pancreatic adenocarcinoma. This open-label, randomised, multi-centre phase II trial explored the role of maintenance sunitinib after first-line chemotherapy in this setting. Methods: Patients with pathologic diagnosis of metastatic pancreatic adenocarcinoma, performance status &gt;50%, no progression after 6 months of chemotherapy were centrally randomised by an independent contract research organisation, which was also responsible for data collection and monitoring, to observation (arm A) or sunitinib at 37.5mg daily until progression or a maximum of 6 months (arm B). The primary outcome measure was the probability of being progression-free at 6 months (PFS-6) from randomisation. Assuming P0 = 10%; P1 = 30%, α .10; β .10, the target accrual was 26 patients per arm. Results: 28 per arm were randomised. One arm B patient had kidney cancer and was excluded. Sunitinib was given for a median of 91 days (7-186). Main grade 3-4 toxicity was thrombocytopenia, neutropenia and hand-foot syndrome (12%), diarrhoea 8%. In arm A versus B, PFS-6 was 3.6% (95% confidence interval (CI): 0-10.6%) and 22.2% (95% CI: 6.2-38.2%; P&lt;0.01); 2 y overall survival was 7.1% (95% CI: 0-16.8%) and 22.9% (95% CI: 5.8-40.0%; P = 0.11), stable disease 21.4% and 51.9% (P = 0.02). Conclusion: This is the first randomised trial on maintenance therapy in metastatic pancreatic adenocarcinoma. The primary end-point was fulfilled and 2 y overall survival was remarkably high, suggesting that maintenance sunitinib is promising and should be further explored in this patient population

Care and Neurorehabilitation in the Disorder of Consciousness: A Model in Progress

The operational model and strategies developed at the Institute S. Anna-RAN to be applied in the care and neurorehabilitation of subjects with disorders of consciousness (DOC) are described. The institute units are sequentially organized to guarantee appropriate care and provide rehabilitation programs adapted to the patients’ clinical condition and individual’s needs at each phase of evolution during treatment in a fast turnover rate. Patients eligible of home care are monitored remotely. Transferring advanced technology to a stage of regular operation is the main mission. Responsiveness and the time windows characterized by better residual responsiveness are identified and the spontaneous/induced changes in the autonomic system functional state and biological parameters are monitored both in dedicated sessions and by means of an ambient intelligence platform acquiring large databases from traditional and innovative sensors and interfaced with knowledge management and knowledge discovery systems. Diagnosis of vegetative state/unresponsive wakefulness syndrome or minimal conscious state and early prognosis are in accordance with the current criteria. Over one thousand patients with DOC have been admitted and treated in the years 1998–2013. The model application has progressively shortened the time of hospitalization and reduced costs at unchanged quality of services

Association of Mild Anemia with Cognitive, Functional, Mood and Quality of Life Outcomes in the Elderly: The “Health and Anemia” Study

BACKGROUND: In the elderly persons, hemoglobin concentrations slightly below the lower limit of normal are common, but scant evidence is available on their relationship with significant health indicators. The objective of the present study was to cross-sectionally investigate the association of mild grade anemia with cognitive, functional, mood, and quality of life (QoL) variables in community-dwelling elderly persons. METHODS: Among the 4,068 eligible individuals aged 65-84 years, all persons with mild anemia (n = 170) and a randomly selected sample of non-anemic controls (n = 547) were included in the study. Anemia was defined according to World Health Organization (WHO) criteria and mild grade anemia was defined as a hemoglobin concentration between 10.0 and 11.9 g/dL in women and between 10.0 and 12.9 g/dL in men. Cognition and functional status were assessed using measures of selective attention, episodic memory, cognitive flexibility and instrumental and basic activities of daily living. Mood and QoL were evaluated by means of the Geriatric Depression Scale-10, the Short-Form health survey (SF-12), and the Functional Assessment of Cancer Therapy-Anemia. RESULTS: In univariate analyses, mild anemic elderly persons had significantly worse results on almost all cognitive, functional, mood, and QoL measures. In multivariable logistic regressions, after adjustment for a large number of demographic and clinical confounders, mild anemia remained significantly associated with measures of selective attention and disease-specific QoL (all fully adjusted p<.046). When the lower limit of normal hemoglobin concentration according to WHO criteria was raised to define anemia (+0.2 g/dL), differences between mild anemic and non anemic elderly persons tended to increase on almost every variable. CONCLUSIONS: Cross-sectionally, mild grade anemia was independently associated with worse selective attention performance and disease-specific QoL ratings

Management of respiratory tract exacerbations in people with cystic fibrosis: Focus on imaging

Respiratory tract exacerbations play a crucial role in progressive lung damage of people with cystic fibrosis, representing a major determinant in the loss of functional lung tissue, quality of life and patient survival. Detection and monitoring of respiratory tract exacerbations are challenging for clinicians, since under- and over-treatment convey several risks for the patient. Although various diagnostic and monitoring tools are available, their implementation is hampered by the current definition of respiratory tract exacerbation, which lacks objective “cut-offs” for clinical and lung function parameters. In particular, the latter shows a large variability, making the current 10% change in spirometry outcomes an unreliable threshold to detect exacerbation. Moreover, spirometry cannot be reliably performed in preschool children and new emerging tools, such as the forced oscillation technique, are still complementary and need more validation. Therefore, lung imaging is a key in providing respiratory tract exacerbation-related structural and functional information. However, imaging encompasses several diagnostic options, each with different advantages and limitations; for instance, conventional chest radiography, the most used radiological technique, may lack sensitivity and specificity in respiratory tract exacerbations diagnosis. Other methods, including computed tomography, positron emission tomography and magnetic resonance imaging, are limited by either radiation safety issues or the need for anesthesia in uncooperative patients. Finally, lung ultrasound has been proposed as a safe bedside option but it is highly operator-dependent and there is no strong evidence of its possible use during respiratory tract exacerbation. This review summarizes the clinical challenges of respiratory tract exacerbations in patients with cystic fibrosis with a special focus on imaging. Firstly, the definition of respiratory tract exacerbation is examined, while diagnostic and monitoring tools are briefly described to set the scene. This is followed by advantages and disadvantages of each imaging technique, concluding with a diagnostic imaging algorithm for disease monitoring during respiratory tract exacerbation in the cystic fibrosis patient

High Risk of Secondary Infections Following Thrombotic Complications in Patients With COVID-19

Background. This study’s primary aim was to evaluate the impact of thrombotic complications on the development of secondary infections. The secondary aim was to compare the etiology of secondary infections in patients with and without thrombotic complications. Methods. This was a cohort study (NCT04318366) of coronavirus disease 2019 (COVID-19) patients hospitalized at IRCCS San Raffaele Hospital between February 25 and June 30, 2020. Incidence rates (IRs) were calculated by univariable Poisson regression as the number of cases per 1000 person-days of follow-up (PDFU) with 95% confidence intervals. The cumulative incidence functions of secondary infections according to thrombotic complications were compared with Gray’s method accounting for competing risk of death. A multivariable Fine-Gray model was applied to assess factors associated with risk of secondary infections. Results. Overall, 109/904 patients had 176 secondary infections (IR, 10.0; 95% CI, 8.8–11.5; per 1000-PDFU). The IRs of secondary infections among patients with or without thrombotic complications were 15.0 (95% CI, 10.7–21.0) and 9.3 (95% CI, 7.9–11.0) per 1000-PDFU, respectively (P = .017). At multivariable analysis, thrombotic complications were associated with the development of secondary infections (subdistribution hazard ratio, 1.788; 95% CI, 1.018–3.140; P = .043). The etiology of secondary infections was similar in patients with and without thrombotic complications. Conclusions. In patients with COVID-19, thrombotic complications were associated with a high risk of secondary infections

Predittori di danno polmonare in fibrosi cistica: indagine su infezione e infiammazione

Background: Inflammation and infection are cornerstones in Cystic fibrosis (CF) lung disease. The research about a biomarker related to disease progression, tracking respiratory exacerbations and effectiveness of antibiotic therapy, is fervent. Aim: this PhD work aimed to investigate: -if plasma and exhaled breath condensate (EBC) levels of Asymmetric dimethilarginine (ADMA) and related metabolites, reportedly related to inflammation in asthma, could associate to disease history, especially respiratory exacerbation onset and effectiveness of treatment; -if lung MRI sequence diffusion weighted imaging (DWI), known to depict tissue inflammation, could discriminate between stable disease and exacerbation, and highlight treatment effectiveness; and if morphological MRI may be influenced by chronic colonization of the airways by P. aeruginosa; -if chronic colonization of the airways by P. aeruginosa may be characterized by an evolution in antibiotic resistance, especially in pediatric CF population; Methods: 4 studies were elaborated -a perspective study on pediatric CF patients, divided into stable and exacerbated patients; clinical data, EBC and plasma were collected in stable group at enrollment, and in exacerbated group before and after antibiotic treatment; ADMA and related metabolites were measured in plasma and EBC through Ultra performance liquidi cromatography, coupled with tandem mass spectrometry, and compared to healthy controls; -a perspective study on pediatric CF patients, in which EBC and clinical data were collected every month for 6 month or till exacerbation; ADMA and related metabolites were measured and correlation with clinical data was tested; -a perspective study on patients divided into stable and exacerbated; spirometry and RMN were performed in exacerbated patients before and after antibiotic treatment and in stable patients at enrollment and after 2 weeks; -a retrospective study about a 4-year period, based upon extraction of clinical and microbiologic data about antibiotic sensitivity of P.aeruginosa in CF patients chronically colonized by P.aeruginosa. Results: -an univocal marker of inflammation could not be identified in EBC; given the absence of differences in ADMA levels among patient groups and healthy controls, and the increase of Citrullin levels in CF compared with controls, a dysregulation of ADMA metabolism was suspected; -various metabolites were higher in plasma of CF patients than in controls; ADMA was increased in exacerbated patients before antibiotic treatment and decreased to levels similar to stable patients after antibiotic treatment; Aginine was increased in all groups, with a further increase after antibiotic treatment; -DWI tracked respiratory exacerbation and effectiveness of treatment; a good correlation to clinical and spirometric parameters was proved; inter and intra-observer agreement were very good; morphologic MRI showed correlation with spirometry and colonization of the airways by P. aeruginosa; -the prevalence of antibiotic sensitivity of P. aeruginosa showed an evolution during the 4-year study period; a decrease in sensitivity especially to fluoroquinolones was proved; sensitivity diminished to a greater extent in pediatic population; increased minimum inhibitory concentrations were found in pediatric patients who underwent more antibiotic courses per year. Conclusions: CF has great phenotipic variability among patients and many factors may influence airways conditions, so a marker can hardly describe this complexity. Moreover, inflammatory pathways alterations are still not completely understood, and deserve futher investigations, given our findings in EBC. Findings on plasma highlighted ADMA role and depicted systemic alterations of the disease. A novel method as metabolomics could enlighten different aspects of the disease in future and help in the stratification of patients. Thoracic MRI with DWI sequence has shown a promising role in inflammation localization and quantification and surely deserves further detailed studies as clinical and research outcome measure.Presupposti: L’infiammazione e l’infezione sono eventi fondamentali alla base della malattia polmonare in Fibrosi cistica (FC) e ne condizionano la progressione. La ricerca di un marker legato alla progressione della malattia e capace di discriminare la necessità di antibiotico-terapia e la risposta a quest’ultima è fervente. Scopo: il lavoro di questo dottorato ha mirato ad indagare -se i livelli plasmatici e nel condensato dell’esalato (EBC) di markers di infiammazione emergenti, finora studiati principalmente nell’asma e nell’infiammazione allergica, come Dimetilarginina asimmetrica (ADMA) e i metaboliti correlati, riflettano l’andamento della malattia in FC, in particolare l’esacerbazione respiratoria e la risposta al trattamento antibiotico; -se la sequenza della RMN diffusion weighted imaging (DWI), nota per un’associazione con l’infiammazione tissutale, applicata al torace, possa distinguere l’esacerbazione respiratoria dalla malattia stabile, ed evidenziare la risposta al trattamento antibiotico e se la RMN toracica sia influenzata dalla colonizzazione cronica da P. aeruginosa; -se la colonizzazione cronica da P. aeruginosa comporti nel tempo un’evoluzione delle resistenze antibiotiche di P. aeruginosa nei pazienti FC, in particolare nella popolazione in età evolutiva. Metodi: sono stati svolti quattro lavori -uno studio prospettico su pazienti pediatrici, suddivisi in stabili ed esacerbati; sono stati raccolti dati clinici, EBC, e plasma negli stabili all’arruolamento e, negli esacerbati, sia prima che dopo terapia antibiotica. ADMA e i metaboliti correlati sono stati misurati nel plasma e nell’EBC tramite cromatografia Ultra performance abbinata a spetrrometria di massa tandem (UPLC-MS/MS) e confrontati con una popolazione di controlli sani; -uno studio prospettico su pazienti pediatrici stabili, con raccolta di EBC ogni 30 giorni, per 6 mesi o fino ad esordio di esacerbazione; ADMA e i metaboliti correlati sono stati dosati e correlati alla funzionalità respiratoria; -uno studio prospettico su pazienti suddivisi in stabili ed esacerbati; dati clinici, spirometria e RMN torace sono state eseguite negli esacerbati prima e dopo terapia antibiotica di 2 settimane, e negli stabili all’arruolamento e dopo due settimane; -uno studio retrospettivo osservazionale di 4 anni basato sull’estrazione di dati clinici e microbiologici relativi alla sensibilità antibiotica di P. aeruginosa in una popolazione di pazienti con colonizzazione cronica da P. aeruginosa. Risultati: -nell’EBC non si è identificato un marker univoco di infiammazione; in considerazione dell’assenza di differenze di ADMA tra i gruppi di pazienti, e rispetto ai controlli sani, e dell’aumento di Citrullina in FC rispetto ai controlli, è stata posta in discussione la disregolazione del metabolismo di ADMA; -nel plasma diversi metaboliti studiati sono risultati più alti in FC che nei controlli; ADMA è risultato aumentato nei pazienti esacerbati, mostrando una riduzione a un livello non distinguibile dai pazienti stabili in seguito a terapia antibiotica; Arginina è risultata auementata in tutti i gruppi, ed in particolare dopo antibioticoterapia; -la DWI ha permesso di distinguere pazienti stabili da esacerbati prima del trattamento, andando incontro a miglioramento dopo terapia antibiotica; ha mostrato buona correlazione con i parametri clinici e spirometrici; la concordanza intra e inter osservatore sono risultate molto buone; la RMN torace ha mostrato correlazione con la funzionalità respiratoria cronica e con la colonizzazione da P. aeruginosa; -le sensibilità antibiotiche di P. aeruginosa hanno subito un’evoluzione nel corso dei 4 anni osservati, con una riduzione marcata in particolare per i fluorochinoloni ed in particolare nella popolazione pediatrica; all’interno della popolazione pediatrica è stato mostrato un peggioramento delle minime concentrazioni inibenti nel gruppo sottoposto a più cicli antibiotici all’anno. Conclusioni: la FC per la sua variabilità fenotipica, per le differenze inter-paziente e per le molteplici fonti di variabilità all’interno delle vie aeree, risulta di difficile descrizione da parte di un singolo marker. Inoltre le alterazioni dei pathway infiammatori non sono ancora completamente noti e compresi e, alla luce di quanto trovato nell’EBC, meritano ulteriore approfondimento. I dati su plasma evidenziano il ruolo di ADMA e rispecchiano le alterazioni sistemiche in corso di malattia. Un approccio innovativo come la metabolomica potrebbe in futuro chiarire diversi aspetti e consentire una migliore stratificazione dei pazienti. La RMN torace con l’utilizzo della sequenza DWI sembra avere un promettente ruolo nella localizzazione e quantificazione dell’infiammazione e meriterà un approfondimento per l’utilizzo come outcome clinico e di ricerca

Predittori di danno polmonare in fibrosi cistica: indagine su infezione e infiammazione

Background: Inflammation and infection are cornerstones in Cystic fibrosis (CF) lung disease. The research about a biomarker related to disease progression, tracking respiratory exacerbations and effectiveness of antibiotic therapy, is fervent. Aim: this PhD work aimed to investigate: -if plasma and exhaled breath condensate (EBC) levels of Asymmetric dimethilarginine (ADMA) and related metabolites, reportedly related to inflammation in asthma, could associate to disease history, especially respiratory exacerbation onset and effectiveness of treatment; -if lung MRI sequence diffusion weighted imaging (DWI), known to depict tissue inflammation, could discriminate between stable disease and exacerbation, and highlight treatment effectiveness; and if morphological MRI may be influenced by chronic colonization of the airways by P. aeruginosa; -if chronic colonization of the airways by P. aeruginosa may be characterized by an evolution in antibiotic resistance, especially in pediatric CF population; Methods: 4 studies were elaborated -a perspective study on pediatric CF patients, divided into stable and exacerbated patients; clinical data, EBC and plasma were collected in stable group at enrollment, and in exacerbated group before and after antibiotic treatment; ADMA and related metabolites were measured in plasma and EBC through Ultra performance liquidi cromatography, coupled with tandem mass spectrometry, and compared to healthy controls; -a perspective study on pediatric CF patients, in which EBC and clinical data were collected every month for 6 month or till exacerbation; ADMA and related metabolites were measured and correlation with clinical data was tested; -a perspective study on patients divided into stable and exacerbated; spirometry and RMN were performed in exacerbated patients before and after antibiotic treatment and in stable patients at enrollment and after 2 weeks; -a retrospective study about a 4-year period, based upon extraction of clinical and microbiologic data about antibiotic sensitivity of P.aeruginosa in CF patients chronically colonized by P.aeruginosa. Results: -an univocal marker of inflammation could not be identified in EBC; given the absence of differences in ADMA levels among patient groups and healthy controls, and the increase of Citrullin levels in CF compared with controls, a dysregulation of ADMA metabolism was suspected; -various metabolites were higher in plasma of CF patients than in controls; ADMA was increased in exacerbated patients before antibiotic treatment and decreased to levels similar to stable patients after antibiotic treatment; Aginine was increased in all groups, with a further increase after antibiotic treatment; -DWI tracked respiratory exacerbation and effectiveness of treatment; a good correlation to clinical and spirometric parameters was proved; inter and intra-observer agreement were very good; morphologic MRI showed correlation with spirometry and colonization of the airways by P. aeruginosa; -the prevalence of antibiotic sensitivity of P. aeruginosa showed an evolution during the 4-year study period; a decrease in sensitivity especially to fluoroquinolones was proved; sensitivity diminished to a greater extent in pediatic population; increased minimum inhibitory concentrations were found in pediatric patients who underwent more antibiotic courses per year. Conclusions: CF has great phenotipic variability among patients and many factors may influence airways conditions, so a marker can hardly describe this complexity. Moreover, inflammatory pathways alterations are still not completely understood, and deserve futher investigations, given our findings in EBC. Findings on plasma highlighted ADMA role and depicted systemic alterations of the disease. A novel method as metabolomics could enlighten different aspects of the disease in future and help in the stratification of patients. Thoracic MRI with DWI sequence has shown a promising role in inflammation localization and quantification and surely deserves further detailed studies as clinical and research outcome measure.Presupposti: L’infiammazione e l’infezione sono eventi fondamentali alla base della malattia polmonare in Fibrosi cistica (FC) e ne condizionano la progressione. La ricerca di un marker legato alla progressione della malattia e capace di discriminare la necessità di antibiotico-terapia e la risposta a quest’ultima è fervente. Scopo: il lavoro di questo dottorato ha mirato ad indagare -se i livelli plasmatici e nel condensato dell’esalato (EBC) di markers di infiammazione emergenti, finora studiati principalmente nell’asma e nell’infiammazione allergica, come Dimetilarginina asimmetrica (ADMA) e i metaboliti correlati, riflettano l’andamento della malattia in FC, in particolare l’esacerbazione respiratoria e la risposta al trattamento antibiotico; -se la sequenza della RMN diffusion weighted imaging (DWI), nota per un’associazione con l’infiammazione tissutale, applicata al torace, possa distinguere l’esacerbazione respiratoria dalla malattia stabile, ed evidenziare la risposta al trattamento antibiotico e se la RMN toracica sia influenzata dalla colonizzazione cronica da P. aeruginosa; -se la colonizzazione cronica da P. aeruginosa comporti nel tempo un’evoluzione delle resistenze antibiotiche di P. aeruginosa nei pazienti FC, in particolare nella popolazione in età evolutiva. Metodi: sono stati svolti quattro lavori -uno studio prospettico su pazienti pediatrici, suddivisi in stabili ed esacerbati; sono stati raccolti dati clinici, EBC, e plasma negli stabili all’arruolamento e, negli esacerbati, sia prima che dopo terapia antibiotica. ADMA e i metaboliti correlati sono stati misurati nel plasma e nell’EBC tramite cromatografia Ultra performance abbinata a spetrrometria di massa tandem (UPLC-MS/MS) e confrontati con una popolazione di controlli sani; -uno studio prospettico su pazienti pediatrici stabili, con raccolta di EBC ogni 30 giorni, per 6 mesi o fino ad esordio di esacerbazione; ADMA e i metaboliti correlati sono stati dosati e correlati alla funzionalità respiratoria; -uno studio prospettico su pazienti suddivisi in stabili ed esacerbati; dati clinici, spirometria e RMN torace sono state eseguite negli esacerbati prima e dopo terapia antibiotica di 2 settimane, e negli stabili all’arruolamento e dopo due settimane; -uno studio retrospettivo osservazionale di 4 anni basato sull’estrazione di dati clinici e microbiologici relativi alla sensibilità antibiotica di P. aeruginosa in una popolazione di pazienti con colonizzazione cronica da P. aeruginosa. Risultati: -nell’EBC non si è identificato un marker univoco di infiammazione; in considerazione dell’assenza di differenze di ADMA tra i gruppi di pazienti, e rispetto ai controlli sani, e dell’aumento di Citrullina in FC rispetto ai controlli, è stata posta in discussione la disregolazione del metabolismo di ADMA; -nel plasma diversi metaboliti studiati sono risultati più alti in FC che nei controlli; ADMA è risultato aumentato nei pazienti esacerbati, mostrando una riduzione a un livello non distinguibile dai pazienti stabili in seguito a terapia antibiotica; Arginina è risultata auementata in tutti i gruppi, ed in particolare dopo antibioticoterapia; -la DWI ha permesso di distinguere pazienti stabili da esacerbati prima del trattamento, andando incontro a miglioramento dopo terapia antibiotica; ha mostrato buona correlazione con i parametri clinici e spirometrici; la concordanza intra e inter osservatore sono risultate molto buone; la RMN torace ha mostrato correlazione con la funzionalità respiratoria cronica e con la colonizzazione da P. aeruginosa; -le sensibilità antibiotiche di P. aeruginosa hanno subito un’evoluzione nel corso dei 4 anni osservati, con una riduzione marcata in particolare per i fluorochinoloni ed in particolare nella popolazione pediatrica; all’interno della popolazione pediatrica è stato mostrato un peggioramento delle minime concentrazioni inibenti nel gruppo sottoposto a più cicli antibiotici all’anno. Conclusioni: la FC per la sua variabilità fenotipica, per le differenze inter-paziente e per le molteplici fonti di variabilità all’interno delle vie aeree, risulta di difficile descrizione da parte di un singolo marker. Inoltre le alterazioni dei pathway infiammatori non sono ancora completamente noti e compresi e, alla luce di quanto trovato nell’EBC, meritano ulteriore approfondimento. I dati su plasma evidenziano il ruolo di ADMA e rispecchiano le alterazioni sistemiche in corso di malattia. Un approccio innovativo come la metabolomica potrebbe in futuro chiarire diversi aspetti e consentire una migliore stratificazione dei pazienti. La RMN torace con l’utilizzo della sequenza DWI sembra avere un promettente ruolo nella localizzazione e quantificazione dell’infiammazione e meriterà un approfondimento per l’utilizzo come outcome clinico e di ricerca

Factors Influencing Burden in Spouse-Caregivers of Patients with Chronic-Acquired Brain Injury

In this cross-sectional study, we assess associated factors of burden in spouse-caregivers of patients with acquired brain injury (ABI) in the chronic phase. 35 spouse-caregivers (71% female, mean age±SD: 55.7±11.1y) of patients with mild/moderate ABI (29% female, mean age±SD: 57.5±10.7y), admitted to the intensive rehabilitation unit of the Institute S. Anna (Crotone, Italy) between January 2013 and December 2017, were contacted 2 years postinjury and asked to complete a series of questionnaires. The outcome measure was the Caregiver Burden Inventory (CBI) test, while several demographical and clinical data were considered as predictive factors. Two years after injury, a high level of burden was reported in 34.2% of spouse-caregivers. Stepwise multiple linear regression analyses revealed that caring for a patient with more severe disability (as measured by the Barthel Index scale) and the family life cycle (from the initial phase of engagement to marriage with adult children) explain the vast majority of variance for higher caregiver burden. The functional clinical status and the stages through which a family may pass over time were identified as areas in which the spouse-caregiver of ABI patients experienced high levels of burden in the chronic phase