Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage ...lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 ± 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 ± 16 years) were enrolled in a case-control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients.
The role and relationship between pro- and anti-inflammatory cytokines represents one of the least studied aspects of the pathogenesis of community-acquired pneumonia (CAP). The aim of the present ...study was to evaluate pro- and anti-inflammatory cytokines at both local (lung) and systemic (blood) levels and their relationship with the severity of the disease on admission and time for a patient to reach clinical stability during hospitalisation.
This was an observational, prospective, cohort study of hospitalised patients with a diagnosis of CAP at the IRCCS Policlinico Hospital, Milan, Italy, between April 2010 and January 2012. Ten pro-inflammatory cytokines (interleukin IL-1, IL-1α, IL-1β, IL-2, IL-6, IL-8, tumor necrosis factor TNFα and interferon IFNγ) and anti-inflammatory cytokines (IL-4 and IL-10) were measured in both serum and exhaled breath condensate within 24 h after hospital admission.
A total of 74 patients (median age: 76 years; gender: 61 % male) were enrolled. The anti- to pro-inflammatory cytokine ratio was reduced in patients with severe disease on admission and prolonged time to reach clinical stability. This was due to lower levels of anti-inflammatory cytokines in the exhaled breath condensate and higher levels of pro-inflammatory cytokines in serum.
Dis-regulation between pro- and anti-inflammatory pathways might be a part of the pathogenic mechanisms that lead to severe infection and worse early clinical outcomes in CAP patients.
Abstract
Background and Aims
Acute kidney Injury (AKI) occurs in more than 50% of patients after lung transplantation (LTx). Our aim was to describe the incidence, risk factors and outcomes ...associated with AKI after LTx in a retrospective monocentric cohort study.
Method
We studied all recipients of LTx (> 16 years of age) occurring at Ospedale Maggiore Policlinico Milano between Jan 1st 2015 and Dec 31st 2017. AKI was defined according to KDIGO classification, eGFR was calculated according to CKD (Chronic Kidney Disease) Epidemiology Collaboration formula and CKD was defined by an eGFR< 60 ml/min per 1.73 m2. Chi square, Fisher exact test, t.-test and logistic regression were used to define risk factors for AKI in the early post-surgical period and for CKD at 1 and 2 years after LTx. AKI-related survival was estimated using Kaplan Meyer model.
Results
Of 78 LTx patients enrolled in our Center, 50% of patients was affected by cystic fibrosis. Median age at transplant was 43 years (27-55); median follow- up was 31 months (20-40). Survival rate was 80.77% at 1 year, 69.23% at 2 years and 66.67% on Dec 31st 2019 (last follow-up).
AKI occurred in 42 (53.85%) patients within the first week after LTx, respectively grade I and II in 12 each (15.38%) and grade III in 18 (23.08%) patients.
Pre-transplant low albumin levels and hypertension were independently associated with AKI at univariate and multivariate (p= 0.0018 and 0.0004 respectively) analysis. Pre-transplant low albumin levels, pre-transplant ECMO-use, hypertension, ECMO-use during transplant surgery were associated with severe AKI in univariate analysis but only pre-transplant hypertension and ECMO-use during transplant surgery were independently associated in the multivariate one (p=0.0266 and 0.0463 respectively).
Survival was significantly reduced in patients affected by AKI (p=0.035); this observation became strongly significant when only mild and moderate (grade I and II) AKI was considered (p=0.0071).
CKD was diagnosed in 38.09% of patients at 1 year and 35.18% at 2 years.
While numerous risk factors were related to the occurrence of CKD at 1 and 2 years after LTx at univariate analysis, only grade III AKI remained independently associated with CKD at multivariate analysis (p= 0.0081 for 1 year-CKD, p=0.0154 for 2 year-CKD).
Conclusions
In our population, AKI after LTx occurred in about half of the patients and was predicted by history of hypertension, low albumin levels and hemodynamic instability during the surgery. Mild-moderate AKI, often clinically underestimated, was strongly associated with reduced survival. Severe forms of AKI were predictive of occurrence of CKD.
Figure: Kaplan Meyer survival curves stratified by presence and grade of AKI.
Lung transplantation is a key therapeutic option for several end-stage lung diseases.
Interventional pulmonology techniques, mostly bronchoscopy, play a key role throughout the whole path of lung ...transplantation, from donor evaluation to diagnosis and management of post-transplant complications.
We carried out a non-systematic, narrative literature review aimed at describing the main indications, contraindications, performance characteristics and safety profile of interventional pulmonology techniques in the context of lung transplantation.
We highlighted the role of bronchoscopy during donor evaluation and described the debated role of surveillance bronchoscopy (with bronchoalveolar lavage and transbronchial biopsy) to detect early rejection, infections and airways complications.
The conventional (transbronchial forceps biopsy) and the new techniques (i.e. cryobiopsy, biopsy molecular assessment, probe-based confocal laser endomicroscopy) can detect and grade rejection. Several endoscopic techniques (e.g. balloon dilations, stent placement, ablative techniques) are employed in the management of airways complications (ischemia and necrosis, dehiscence, stenosis and malacia).
First line pleural interventions (i.e. thoracentesis, chest tube insertion, indwelling pleural catheters) may be useful in the context of early and late pleural complications occurring after lung transplantation.
High quality studies are advocated to define endoscopic standard protocols and thus help improving long-term prognostic outcomes of lung transplant recipients.
•Bronchoscopy plays a key role throughout the path of lung transplantation.•Cryobiopsy and pCLE are new techniques to detect and grade rejection.•The optimal endoscopic management of airways complications is still debated.•First line pleural interventions help manage transplant pleural complications.•High quality studies are needed to define endoscopic standard protocols.
Introduction
The postoperative hemodynamic management after lung transplant (LUTX) is guided by limited evidence. We aimed to describe and evaluate risk factors and outcomes of postoperative ...vasoactive support of LUTX recipients.
Methods
In a single‐center retrospective analysis of consecutive adult LUTX, two cohorts were identified: (1) patients needing prolonged vasoactive support (>12 h from ICU admission) (VASO+); (2) or not (VASO−). Postoperative hemodynamic characteristics were thoroughly analyzed. Risk factors and outcomes of VASO+ versus VASO− cohorts were assessed by multivariate logistic regression and propensity score matching.
Results
One hundred and thirty‐eight patients were included (86 (62%) VASO+ versus 52 (38%) VASO−). Vasopressors (epinephrine, norepinephrine, dopamine) were used in the first postoperative days (vasoactive inotropic score at 12 h: 6 4–12), while inodilators (dobutamine, levosimendan) later. Length of vasoactive support was 3 2–4 days. Independent predictors of vasoactive use were: LUTX indication different from cystic fibrosis (p = .003), higher Oto score (p = .020), longer cold ischemia time (p = .031), but not preoperative cardiac catheterization. VASO+ patients showed concomitant hemodynamic and graft impairment, with longer mechanical ventilation (p = .010), higher primary graft dysfunction (PGD) grade at 72 h (PGD grade > 0 65% vs. 31%, p = .004, OR 4.2 1.54–11.2), longer ICU (p < .001) and hospital stay (p = .013). Levosimendan as a second‐line inodilator appeared safe.
Conclusions
Vasoactive support is frequently necessary after LUTX, especially in recipients of grafts of lesser quality. Postoperative hemodynamic dysfunction requiring vasopressor support and graft dysfunction may represent a clinical continuum with immediate and long‐term consequences. Further studies may elucidate if this represents a possible treatable condition.
•Lower right ventricle ejection fraction and BSA, O2 needs, diabetes are associated with ECMO.•ECMO patients had fivefold transfusions and had PGD grade >0 at 72 h more frequently.•ECMO patients had ...longer mechanical ventilation, ICU and hospital LOS.
Predictors and outcomes of intraoperative extracorporeal membrane oxygenation (ECMO) during lung transplantation (LUTX) for cystic fibrosis (CF) are unknown.
We retrospectively collected the clinical data at enlistment of the CF patients who underwent double LUTX from January 2013 to December 2018 at an Italian tertiary referral center. We compared blood transfusions, incidence of primary graft dysfunction (PGD), duration of mechanical ventilation, intensive care unit (ICU) length of stay (LOS), hospital LOS and survival of ECMO and non-ECMO patients. Chi-square, Kruskal-Wallis, and log-rank tests were used.
Twenty-eight (40%) of the 70 included patients needed intraoperative central veno-arterial ECMO with postoperative veno-venous prolongation in 6 subjects. Lower right ventricle ejection fraction (p = 0.013, OR 0.92(0.86–0.98)), higher oxygen requirement (p = 0.026, OR 1.39(1.01–1.90)), lower body surface area (p = 0.044, OR 0.05(0.00–1.03)), and CF-related diabetes (p = 0.044, OR 2.81(1.03–7.66)) were associated with intraoperative ECMO. Compared to non-ECMO patients, ECMO patients needed almost fivefold intraoperative transfusion (2227 mL vs. 570 mL, p<0.001) and had PGD grade > 0 at 72 h more frequently (16/57% vs. 12/28%, p = 0.017, OR 3.33(1.22–9.09)). Mechanical ventilation, ICU LOS and hospital LOS were significantly longer in ECMO patients. Survival at follow-up (651(326–1277) days) of ECMO and non-ECMO patients was 78% vs. 83%, respectively (OR 0.73 (0.21–2.46), p = 0.616, log-rank test p = 0.498).
: Pre-operative risk assessment and clinical planning should be done according to the predictors above. While undeniably useful as a life-saving procedure, ECMO during LUTX for CF is associated with worsened short-term outcomes. ECMO should be implemented weighing its risk and benefits.
Introduction
The clinical trajectory of post-operative acute kidney injury (AKI) following lung transplantation for cystic fibrosis is unknown.
Methods
Incidence and risk factors for post-operative ...AKI, acute kidney disease (AKD) and chronic kidney disease (CKD) were retrospectively analyzed in cystic fibrosis patients undergoing lung transplantation. Logistic regressions, Chi-square, Cuzick rank tests, and Cox-proportional hazard models were used.
Results
Eighty-three patients were included. Creatinine peaked 32–4 days after transplantation, with 15(18%), 15(18%), and 20(24%) patients having post-operative AKI stages 1, 2, and 3, while 15(18%), 19(23%) and 10(12%) developed AKD stage 1, stage 2 and 3, respectively. Higher AKI stage was associated with worsening AKD (
p
= 0.009) and CKD (
p
= 0.015) stages. Of the 50 patients with AKI, 32(66%) transitioned to AKD stage > 0, and then 27 (56%) to CKD stage > 1. Female sex, extracorporeal membrane oxygenation support as a bridge to lung transplant and at the end of the surgery, the use of intraoperative blood components, and cold-ischemia time were associated with increased risk of post-operative AKI and AKD. Higher AKI stage prolonged invasive mechanical ventilation (
p
= 0.0001), ICU stay (
p
= 0.0001), and hospital stay (
p
= 0.0001), and increased the incidence of primary graft dysfunction (
p
= 0.035). Both AKI and AKD stages > 2 worsened long-term survival with risk ratios of 3.71 (1.34–10.2),
p
= 0.0131 and 2.65(1.02–6.87),
p
= 0.0443, respectively.
Discussion
AKI is frequent in cystic fibrosis patients undergoing lung transplantation, it often evolves to AKD and to chronic kidney disease, thereby worsening short- and long-term outcomes.
Graphical abstract
Donation after cardiac death (DCD) donors are still subject of studies. In this prospective cohort trial, we compared outcomes after lung transplantation (LT) of subjects receiving lungs from DCD ...donors with those of subjects receiving lungs from donation after brain death (DBD) donors (ClinicalTrial.gov: NCT02061462). Lungs from DCD donors were preserved
through normothermic ventilation, as per our protocol. We enrolled candidates for bilateral LT ≥14 years. Candidates for multi-organ or re-LT, donors aged ≥65 years, DCD category I or IV donors were excluded. We recorded clinical data on donors and recipients. Primary endpoint was 30-day mortality. Secondary endpoints were: duration of mechanical ventilation (MV), intensive care unit (ICU) length of stay, severe primary graft dysfunction (PGD3) and chronic lung allograft dysfunction (CLAD). 121 patients (110 DBD Group, 11 DCD Group) were enrolled. 30-day mortality and CLAD prevalence were nil in the DCD Group. DCD Group patients required longer MV (DCD Group: 2 days, DBD Group: 1 day,
= 0.011). ICU length of stay and PGD3 rate were higher in DCD Group but did not significantly differ. LT with DCD grafts procured with our protocols appears safe, despite prolonged ischemia times.
The American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA) suggested two sets of criteria in 2001 and 2007 to define clinical stability in community-acquired pneumonia ...(CAP). The present study aimed to evaluate the level of agreement between these two sets of criteria and how well they can predict clinical outcomes. A retrospective cohort study was carried out of 487 consecutive patients hospitalised with CAP. Level of agreement was tested using a survival curve analysis, while prediction of outcomes at 30-day follow-up was evaluated through receiver operating characteristic (ROC) analysis. A discrepancy between ATS 2001 and ATS/IDSA 2007 criteria in identifying clinical stability was detected in 62% of the patients. The median (interquartile range) time to clinical stability was 2 (1-4) days based on ATS 2001 and 3 (2-5) days based on ATS/IDSA 2007 criteria (p = 0.012). The daily distribution of patients who reached clinical stability evaluated with both sets was different (p = 0.002). The ROC analysis showed an area under the curve of 0.705 for the ATS 2001 criteria and 0.714 for ATS/IDSA 2007 criteria (p = 0.645). ATS 2001 and ATS/IDSA 2007 criteria for clinical stability in hospitalised patients with CAP are clinically equivalent and both can be used in clinical practice as well as in clinical research.
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