A virtual crossmatch-based strategy for perioperative desensitisation in lung transplant recipients with pre-formed donor-specific antibodies: 3-year outcome.

BACKGROUND: Pre-formed donor-specific antibodies (DSAs) are associated with worse outcome after lung transplantation (LTx) and might limit access to LTx. A virtual crossmatch-based strategy for perioperative desensitisation protocol has been used for immunised LTx candidates since 2012 at Foch Hospital (Suresnes, France). We compared the outcome of desensitised LTx candidates with high DSA mean fluorescence intensity and those with low or no pre-formed DSAs, not desensitised. METHODS: For all consecutive LTx recipients (January 2012 to March 2018), freedom from chronic lung allograft dysfunction (CLAD) and graft survival were assessed using Kaplan-Meier analysis and Cox multivariate analysis. RESULTS: We compared outcomes for desensitised patients with high pre-formed DSAs (n=39) and those with no (n=216) or low pre-formed DSAs (n=66). The desensitisation protocol decreased the level of immunodominant DSA (class I/II) at 1, 3 and 6 months post-LTx (p<0.001, p<0.01 and p<0.001, respectively). Freedom from CLAD and graft survival at 3 years was similar in the desensitised group as a whole and other groups. Nevertheless, incidence of CLAD was higher with persistent high-level DSAs than cleared high-level (p=0.044) or no DSAs (p=0.014). Conversely, graft survival was better with cleared high DSAs than persistent high-level, low-level and no pre-formed DSAs (p=0.019, p=0.025 and p=0.044, respectively). On multivariate analysis, graft survival was associated with cleared high DSAs (hazard ratio 0.12, 95% CI 0.02-0.85 versus no DSAs; p=0.035) and CLAD with persistent DSAs (3.04, 1.02-9.17 versus no pre-formed DSAs; p=0.048). CONCLUSION: The desensitisation protocol in LTx recipients with high pre-formed DSAs was associated with satisfactory outcome, with cleared high pre-formed DSAs after desensitisation identified as an independent predictor of graft survival.

High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post-transplant mortality.

Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, "High Emergency Lung Transplantation" (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non-HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post-LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.

Procalcitonin for diagnosis of bacterial pneumonia in critically ill patients during 2009 H1N1 influenza pandemic: a prospective cohort study, systematic review and individual patient data meta-analysis.

INTRODUCTION: Procalcitonin (PCT) is helpful for diagnosing bacterial infections. The diagnostic utility of PCT has not been examined thoroughly in critically ill patients with suspected H1N1 influenza. METHODS: Clinical characteristics and PCT were prospectively assessed in 46 patients with pneumonia admitted to medical ICUs during the 2009 and 2010 influenza seasons. An individual patient data meta-analysis was performed by combining our data with data from five other studies on the diagnostic utility of PCT in ICU patients with suspected 2009 pandemic influenza A(H1N1) virus infection identified by performing a systematic literature search. RESULTS: PCT levels, measured within 24 hours of ICU admission, were significantly elevated in patients with bacterial pneumonia (isolated or coinfection with H1N1; n = 77) (median = 6.2 µg/L, interquartile range (IQR) = 0.9 to 20) than in patients with isolated H1N1 influenza pneumonia (n = 84; median = 0.56 µg/L, IQR = 0.18 to 3.33). The area under the curve of the receiver operating characteristic curve of PCT was 0.72 (95% confidence interval (CI) = 0.64 to 0.80; P < 0.0001) for diagnosis of bacterial pneumonia, but increased to 0.76 (95% CI = 0.68 to 0.85; P < 0.0001) when patients with hospital-acquired pneumonia and immune-compromising disorders were excluded. PCT at a cut-off of 0.5 µg/L had a sensitivity (95% CI) and a negative predictive value of 80.5% (69.9 to 88.7) and 73.2% (59.7 to 84.2) for diagnosis of bacterial pneumonia, respectively, which increased to 85.5% (73.3 to 93.5) and 82.2% (68.0 to 92.0) in patients without hospital acquired pneumonia or immune-compromising disorder. CONCLUSIONS: In critically ill patients with pneumonia during the influenza season, PCT is a reasonably accurate marker for detection of bacterial pneumonia, particularly in patients with community-acquired disease and without immune-compromising disorders, but it might not be sufficient as a stand-alone marker for withholding antibiotic treatment.

Immune diffuse alveolar hemorrhage: a retrospective assessment of a diagnostic scale.

BACKGROUND: Initiating early steroid treatment in patients with immune diffuse alveolar hemorrhage (DAH) is a key aspect of early management. However, steroid initiation is often delayed until the results of immunological markers and/or tissue biopsy have been obtained, which could contribute to poor outcomes. We previously developed a clinical score allowing for the early diagnosis of DAH of immune causes. However, this score has not been validated in an independent cohort of patients. The aim of this study was to assess the validity of this diagnostic score using an independent cohort of patients admitted for DAH of immune and nonimmune causes. METHODS: We conducted a retrospective cohort study of patients admitted between January 2002 and December 2009 for DAH of immune and nonimmune causes. RESULTS: Forty-six patients were included in the study, with 12 patients having immune DAH and 34 patients with nonimmune DAH. Application of our previously validated clinical scale of immune DAH to this independent population of patients yielded an area under the ROC curve of 0.95 [0.90-1.01]. A score ≥4/10 was associated with the best performances of this scale: sensitivity = 1.00 [0.73-1.00], specificity = 0.88 [0.72-0.97], positive predictive value = 0.75 [0.48-0.93], and negative predictive value = 1.00 [0.88-1.00]. CONCLUSION: While immunological tests and tissue biopsy results are pending, deciding whether to initiate an immunosuppressive treatment is challenging. The initiation of early corticosteroid treatment is warranted in patients with immune DAH and could improve outcomes. This study confirms that this score allows for a good discrimination between patients with immune and nonimmune DAH. Because this series has several limitations, including its single-center and retrospective nature, the small number of patients included, and the lack of therapeutic intervention, a prospective evaluation of this score is warranted to ascertain whether it can improve the adequacy of early treatment strategies and thus improve the outcomes of DAH patients.

Heated and humidified high-flow oxygen therapy reduces discomfort during hypoxemic respiratory failure.

BACKGROUND: Non-intubated critically ill patients are often treated by high-flow oxygen for acute respiratory failure. There is no current recommendation for humidification of oxygen devices. METHODS: We conducted a prospective randomized trial with a final crossover period to compare nasal airway caliber and respiratory comfort in patients with acute hypoxemic respiratory failure receiving either standard oxygen therapy with no humidification or heated and humidified high-flow oxygen therapy (HHFO2) in a medical ICU. Nasal airway caliber was measured using acoustic rhinometry at baseline, after 4 and 24 hours (H4 and H24), and 4 hours after crossover (H28). Dryness of the nose, mouth, and throat was auto-evaluated and assessed blindly by an otorhinolaryngologist. After the crossover, the subjects were asked which system they preferred. RESULTS: Thirty subjects completed the protocol and were analyzed. Baseline median oxygen flow was 9 and 12 L/min in the standard and HHFO2 groups, respectively (P = .21). Acoustic rhinometry measurements showed no difference between the 2 systems. The dryness score was significantly lower in the HHFO2 group at H4 (2 vs 6, P = .007) and H24 (0 vs 8, P = .004). During the crossover period, dryness increased promptly after switching to standard oxygen and decreased after switching to HHFO2 (P = .008). Sixteen subjects (53%) preferred HHFO2 (P = .01), especially those who required the highest flow of oxygen at admission (P = .05). CONCLUSIONS: Upper airway caliber was not significantly modified by HHFO2, compared to standard oxygen therapy, but HHFO2 significantly reduced discomfort in critically ill patients with respiratory failure. The system is usually preferred over standard oxygen therapy.

Trans-arterial embolization for hemoptysis in lung transplant recipients.

INTRODUCTION: Hemoptysis isn't rare in lung transplant recipients (LTR). Yet, trans-arterial embolization (TAE) in LTR has been rarely reported in the literature. The aim of the study was to present the feasibility and outcomes of TAE for hemoptysis in LTR. MATERIALS AND METHODS: Retrospective study of all LTR who underwent TAE for hemoptysis in our single institution between 2005 and 2020. RESULTS: A total of 787 patients underwent lung transplantation between 2005 and 2020. Fifteen LTR underwent 21 TAE for hemoptysis in a median delay of 42 days after LT. TAE was performed within a year after LT in 13 patients (86.7%) with 12 of those patients having concomitant severe ischemic airway injury with necrosis and anastomotic dehiscence. Bronchoscopy confirmed bronchial anastomoses has being the source of the bleeding in 11 LTR (84.6%). Restoration of bronchial vascularization was highlighted in 13 patients (87%). Despite TAE, bronchial anastomosis healing was observed in all surviving patients with anastomotic dehiscence in a median delay of 43 days. CONCLUSION: In our experience, hemoptysis requiring TAE in LTR was rare, frequently occurring in the first weeks after LT, and seemed associated with anastomotic ischemia and dehiscence. Bleeding mainly originated from ischemic bronchial anastomosis through the restoration of the bronchial artery circulation. Our results suggest that bronchial arteriography should be routinely proposed in such patients in the event of hemoptysis.

Procalcitonin to Reduce Antibiotic Exposure during Acute Chest Syndrome in Adult Patients with Sickle-Cell Disease.

Acute chest syndrome (ACS) is a major complication of sickle-cell disease. Bacterial infection is one cause of ACS, so current guidelines recommend the routine use of antibiotics. We performed a prospective before-after study in medical wards and an intensive-care unit (ICU). During the control phase, clinicians were blinded to procalcitonin concentration results. We built an algorithm using the obtained measurements to hasten antibiotic cessation after three days of treatment if bacterial infection was not documented, and procalcitonin concentrations were all <0.5 µg/L. During the intervention period, the procalcitonin algorithm was suggested to physicians as a guide for antibiotic therapy. The primary endpoint was the number of days alive without antibiotics at Day 21. One-hundred patients were analyzed (103 ACS episodes, 60 in intervention phase). Possible or proven lung infection was diagnosed during 13% of all ACS episodes. The number of days alive without antibiotics at Day 21 was higher during the intervention phase: 15 [14-18] vs. 13 [13,14] days (p = 0.001). More patients had a short (≤3 days) antibiotic course during intervention phase: 31% vs 9% (p = 0.01). There was neither infection relapse nor pulmonary superinfection in the entire cohort. A procalcitonin-guided strategy to prescribe antibiotics in patients with ACS may reduce antibiotic exposure with no apparent adverse outcomes.

Characteristics of Donor-Specific Antibodies Associated With Antibody-Mediated Rejection in Lung Transplantation.

Although donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) are frequently found in recipients after lung transplantation (LT), the characteristics of DSA which influence antibody-mediated rejection (AMR) in LT are not fully defined. We retrospectively analyzed 206 consecutive LT patients of our center (2010-2013). DSAs were detected by using luminex single antigen beads assay and mean fluorescence intensity was assessed. Within the study population, 105 patients had positive DSA. Patients with and without AMR (AMRPos, n = 22, and AMRNeg, n = 83, respectively) were compared. AMRPos patients had significantly greater frequencies of anti-HLA DQ DSA (DQ DSA) than AMRNeg patients (95 vs 58%, respectively, p < 0.0001). Compared to AMRNeg patients, AMRPos patients had higher DQ DSA sum MFI [7,332 (2,067-10,213) vs 681 (0-1,887), p < 0.0001]. DQ DSA when associated with AMR, had more frequent graft loss and chronic lung allograft dysfunction (CLAD). These data suggest (i) that DSA characteristics clearly differ between AMRPos and AMRNeg patients and (ii) the deleterious impact of DQ DSA on clinical outcome.

Bedside Lung Ultrasound During Acute Chest Syndrome in Sickle Cell Disease.

Lung ultrasound (LU) is increasingly used to assess pleural and lung disease in intensive care unit (ICU) and emergency unit at the bedside. We assessed the performance of bedside chest radiograph (CR) and LU during severe acute chest syndrome (ACS), using computed tomography (CT) as the reference standard. We prospectively explored 44 ACS episodes (in 41 patients) admitted to the medical ICU. Three imaging findings were evaluated (consolidation, ground-glass opacities, and pleural effusion). A score was used to quantify and compare loss of lung aeration with each technique and assess its association with outcome. A total number of 496, 507, and 519 lung regions could be assessed by CT scan, bedside CR, and bedside LU, respectively. Consolidations were the most common pattern and prevailed in lung bases (especially postero-inferior regions). The agreement with CT scan patterns was significantly higher for LU as compared to CR (κ coefficients of 0.45 ±â€Š0.03 vs 0.30 ±â€Š0.03, P < 0.01 for the parenchyma, and 0.73 ±â€Š0.08 vs 0.06 ±â€Š0.09, P < 0.001 for pleural effusion). The Bland and Altman analysis showed a nonfixed bias of -1.0 (P = 0.12) between LU score and CT score whereas CR score underestimated CT score with a fixed bias of -5.8 (P < 0.001). The specificity for the detection of consolidated regions or pleural effusion (using CT scan as the reference standard) was high for LU and CR, whereas the sensitivity was high for LU but low for CR. As compared to others, ACS patients with an LU score above the median value of 11 had a larger volume of transfused and exsanguinated blood, greater oxygen requirements, more need for mechanical ventilation, and a longer ICU length of stay. LU outperformed CR for the diagnosis of consolidations and pleural effusion during ACS. Higher values of LU score identified patients at risk of worse outcome.

Diffuse alveolar hemorrhage in immunocompetent patients: etiologies and prognosis revisited.

BACKGROUND: Diffuse alveolar hemorrhage (DAH) represents a diagnostic challenge of acute respiratory failure. Prompt identification of the underlying cause of DAH and initiation of appropriate treatment are required in order to prevent acute respiratory failure and irreversible loss of renal function. More than 100 causes of DAH have been reported. However, the relative frequency and the differential presentation of those causes have been poorly documented, as well as their respective prognosis. METHODS: We retrospectively reviewed the charts of 112 consecutive patients hospitalized for DAH in a tertiary referral center over a 30-year period. RESULTS: Twenty-four causes of DAH were classified into four etiologic groups: immune (n = 39), congestive heart failure (CHF; n = 33), miscellaneous (n = 26), and idiopathic DAH (n = 14). Based on this classification, clinical and laboratory features of DAH differed on hospital admission. Patients with immune DAH had more frequent pulmonary-renal syndrome (p < 0.001), extra-pulmonary symptoms (p < 0.01), and lower blood hemoglobin level than others (p < 0.001). Patients with CHF-related DAH were older and received more anticoagulant treatments than others (p < 0.05). Those with miscellaneous causes of DAH exhibited a shorter prodromal phase (p < 0.001) and had more frequent hemoptysis >200 mL (p < 0.05). Patients with idiopathic DAH had more bronchoalveolar lavage siderophages (p < 0.01). In-hospital mortality was 24.1%, ranging from 7.1% in patients with idiopathic DAH to 36.4% in those with CHF. CONCLUSIONS: Arbitrary classification of DAH in four etiologic groups gives the opportunity to underline distinct presentations and outcomes of various causes of DAH.