The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an ...investigator‐initiated single‐center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS‐free survival in intention‐to‐treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per‐protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy‐proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS‐free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus‐based protocols but also a potentially higher rate of drug‐related serious adverse events.
Everolimus and mycophenolate mofetil have different adverse event profiles when used in de novo lung transplantation.
Increasing worldwide development of antimicrobial resistance and the association of resistance development and antibiotic overuse make it necessary to seek strategies for safely reducing antibiotic ...use and selection pressure. In a first step, in a non-interventional study, the antibiotic prescription rates, initial procalcitonin (PCT) levels and outcome of 702 patients presenting with acute respiratory infection at 45 primary care physicians were observed. The second part was a randomised controlled non-inferiority trial comparing standard care with PCT-guided antimicrobial treatment in 550 patients in the same setting. Antibiotics were recommended at a PCT threshold of 0.25 ng·mL(-1). Clinical overruling was permitted. The primary end-point for non-inferiority was number of days with significant health impairment after 14 days. Antibiotics were prescribed in 30.3% of enrolled patients in the non-interventional study. In the interventional study, 36.7% of patients in the control group received antibiotics as compared to 21.5% in the PCT-guided group (41.6% reduction). In the modified intention-to-treat analysis, the numbers of days with significant health impairment were similar (mean 9.04 versus 9.00 for PCT-guided and control group, respectively; difference 0.04; 95% confidence interval -0.73-0.81). This was also true after adjusting for the most important confounders. In the PCT group, advice was overruled in 36 cases. There was no significant difference in primary end-point when comparing the PCT group treated as advised, the overruled PCT group and the control group (9.008 versus 9.250 versus 9.000 days; p = 0.9605). A simple one-point PCT measurement for guiding decisions on antibiotic treatment is non-inferior to standard treatment in terms of safety, and effectively reduced the antibiotic treatment rate by 41.6%.
Combination therapy may improve outcome in patients with severe pulmonary arterial hypertension (PAH). PAH patients were treated according to a goal-oriented therapeutic strategy. Patients who did ...not reach the treatment goals with monotherapy received combination treatment according to a predefined strategy, including bosentan, sildenafil and inhaled iloprost. Intravenous iloprost and lung transplantation were reserved for treatment failures. End points were overall survival, transplantation-free survival, and survival free from transplantation and intravenous prostanoid treatment. Between January 2002 and December 2004, 123 consecutive patients with PAH were treated according to the novel approach. Survival at 1, 2 and 3 yrs was 93.0, 83.1 and 79.9%, respectively, which was significantly better than the survival of a historical control group, as well as the expected survival. Compared to the historical control group, the use of combination treatment also significantly improved the combined end point of death, lung transplantation and need for intravenous iloprost treatment. In conclusion, a therapeutic approach utilising combinations of bosentan, sildenafil and inhaled iloprost in conjunction with a goal-oriented treatment strategy provides acceptable long-term results in patients with severe pulmonary arterial hypertension, and reduces the need for intravenous prostaglandin treatment and lung transplantation.
Community-acquired pneumonia remains a major cause of mortality in developed countries. There is much discrepancy in the literature regarding factors influencing the outcome in the elderly ...population. Data were derived from a multicentre prospective study initiated by the German Competence Network for Community-Acquired Pneumonia. Patients with community-acquired pneumonia (n = 2,647; 1,298 aged < 65 yrs and 1,349 aged > or = 65 yrs) were evaluated, of whom 72.3% were hospitalised and 27.7% treated in the community. Clinical history, residence status, course of disease and antimicrobial treatment were prospectively documented. Microbiological investigations included cultures and PCR of respiratory samples and blood cultures. Factors related to mortality were included in multivariate analyses. The overall 30-day mortality was 6.3%. Elderly patients exhibited a significantly higher mortality rate that was independently associated with the following: age; residence status; confusion, urea, respiratory frequency and blood pressure (CURB) score; comorbid conditions; and failure of initial therapy. Increasing age remained predictive of death in the elderly. Nursing home residents showed a four-fold increased mortality rate and an increased rate of gram-negative bacillary infections compared with patients dwelling in the community. The CURB score and cerebrovascular disease were confirmed as independent predictors of death in this subgroup. Age and residence status are independent risk factors for mortality after controlling for comorbid conditions and disease severity. Failure of initial therapy was the only modifiable prognostic factor.
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Objective. The study was performed to validate the CURB, CRB and CRB‐65 scores for the prediction of death from community‐acquired pneumonia (CAP) in both the hospital and out‐patient setting.
...Design. Data were derived from a large multi‐centre prospective study initiated by the German competence network for community‐acquired pneumonia (CAPNETZ) which started in March 2003 and were censored for this analysis in October 2004.
Setting. Out‐ and in‐hospital patients in 670 private practices and 10 clinical centres.
Subjects. Analysis was done for n = 1343 patients (n = 208 out‐patients and n = 1135 hospitalized) with all data sets completed for the calculation of CURB and repeated for n = 1967 patients (n = 482 out‐patients and n = 1485 hospitalized) with complete data sets for CRB and CRB‐65.
Intervention. None. 30‐day mortality from CAP was determined by personal contacts or a structured interview.
Results. Overall 30‐day mortality was 4.3% (0.6% in out‐patients and 5.5% in hospitalized patients, P < 0.0001). Overall, the CURB, CRB and CRB‐65 scores provided comparable predictions for death from CAP as determined by receiver–operator‐characteristics (ROC) curves. However, in hospitalized patients, CRB misclassified 26% of deaths as low risk patients. Availability of the CRB‐65 score (90%) was far superior to that of CURB (65%), due to missing blood urea nitrogen values (P < 0.001).
Conclusions. Both the CURB and CRB‐65 scores can be used in the hospital and out‐patients setting to assess pneumonia severity and the risk of death. Given that the CRB‐65 is easier to handle, we favour the use of CRB‐65 where blood urea nitrogen is unavailable.
Background
Addition of assessment of comorbid diseases (‘D’) and oxygen saturation (‘S’) to the CRB‐65 score has been recommended to improve its accuracy for risk stratification in community‐acquired ...pneumonia (CAP). The aim of this study was to validate the resulting DS‐CRB‐65 score in a large cohort of patients with CAP.
Methods
A total of 4432 patients prospectively enrolled in the CAPNETZ cohort were included in this study. Predefined end points were 28‐day mortality, requirement for mechanical ventilation or vasopressors (MV/VS) and requirement for MV/VS or intensive care unit admission (MV/VS/ICU). Receiver operating characteristic curve analysis was used to determine the accuracy of the CRB‐65 score and the addition of D (extra‐pulmonary comorbidities) and S (oxygen saturation <90% or partial pressure of oxygen <8 kPa). Binary logistic regression and the method of Hanley and McNeil were used to compare the criteria.
Results
The mortality rate was 4.0%, and 4.2% of patients required MV/VS and 6.6% required MV/VS/ICU. After multivariate analysis, D and S independently were added to the CRB‐65 criteria for mortality prediction, but only S improved prediction of MV/VS and MV/VS/ICU (P < 0.001 for all). The area under the curve of the CRB‐65 score was significantly improved by adding D and S for all end points (P < 0.02). Amongst patients who died or required MV/VS despite a CRB‐65 score of 0, 64–80% would have been identified by the DS‐CRB‐65 score.
Conclusions
The addition of assessment of oxygenation and comorbidities significantly improved the prognostic accuracy of the CRB‐65 score. Consequently, the DS‐CRB‐65 score may have a useful role in risk stratification algorithms for CAP.
We report on the use of veno‐arterial extracorporeal membrane oxygenation (ECMO) as a bridging strategy to lung transplantation in awake and spontaneously breathing patients. All five patients ...described in this series presented with cardiopulmonary failure due to pulmonary hypertension with or without concomitant lung disease. ECMO insertion was performed under local anesthesia without sedation and resulted in immediate stabilization of hemodynamics and gas exchange as well as recovery from secondary organ dysfunction. Two patients later required endotracheal intubation because of bleeding complications and both of them eventually died. The other three patients remained awake on ECMO support for 18–35 days until the time of transplantation. These patients were able to breathe spontaneously, to eat and drink, and they received passive and active physiotherapy as well as psychological support. All of them made a full recovery after transplantation, which demonstrates the feasibility of using ECMO support in nonintubated patients with cardiopulmonary failure as a bridging strategy to lung transplantation.
The use of ECMO in fully awake patients is a promising bridging strategy for patients with terminal cardiopulmonary failure.
Atrial fibrillation (AF) is common among patients in the intensive care unit (ICU) and can be triggered by severe illness or preexisting conditions. It is debated if AF is an independent predictor of ...poor outcome.
Data derives from a single center retrospective registry including all patients with a stay on the medical ICU for >24 h. The primary endpoint was ICU survival. Secondary endpoints included receiving mechanical support (renal, respiratory or circulatory), hemodynamic parameters during AF, rate and rhythm control strategies, anticoagulation, and documentation.
A total of 616 patients (male gender 62.3%, median age 75 years) were included in our analysis. New-onset AF was diagnosed in 87 patients (14.1%), 136 (22.1%) presented with preexisting AF, and 393 (63.8%) did not develop AF. Initial episodes of new-onset AF exhibited higher hemodynamic instability than episodes in preexisting cases, with elevated heart rates and increased catecholamine doses (both p < 0.001). ICU survival in new-onset AF was 80.5% (70/87) compared to 92.4% (363/393) in patients without AF (OR 0.340, CI 0.182–0.658, p < 0.001). Likewise, ICU survival in preexisting AF was 86.8% (118/136) was significantly lower compared to no AF (OR 0.542, CI 0.290–0.986, p = 0.050*). Independent predictors of ICU survival for patients were atrial fibrillation (p = 0.016), resuscitation before or during ICU stay (p < 0.001), and receiving acute dialysis on ICU (p = 0.002).
ICU survival is noticeably lower in patients with new-onset or preexisting atrial fibrillation compared to those without. Patients who develop new-onset AF during their ICU stay warrant special attention for both short-term and long-term care strategies.
•Parents on the intensive care unit frequently suffer from atrial fibrillation.•Studies on this subject often focus on new onset atrial fibrillation. Data on preexisting atrial fibrillation is limited.•We present our registry including >600 parents on new and preexisting atrial fibrillation in the ICU setting.•New onset atrial fibrillation differs from preexisting atrial fibrillation .Both are predictors of survival.•Not all diagnoses of atrial fibrillation are communicated at discharge.
Background. High functional antibody responses, establishment of immunologic memory, and unambiguous efficacy in infants suggest that an initial dose of conjugated pneumococcal polysaccharide (PnC) ...vaccine may be of value in a comprehensive adult immunization strategy. Methods. We compared the immunogenicity and safety of 7-valent PnC vaccine (7vPnC) with that of 23-valent pneumococcal polysaccharide vaccine (PPV) in adults ⩾ 70 years of age who had not been previously vaccinated with a pneumococcal vaccine. One year later, 7vPnC recipients received a booster dose of either 7vPnC (the 7vPnC/7vPnC group) or PPV (the 7vPnC/PPV group), and PPV recipients received a booster dose of 7vPnC (the PPV/7vPnC group). Immune responses were compared for each of the 7 serotypes common to both vaccines. Results. Antipolysaccharide enzyme-linked immunosorbent assay antibody concentrations and opsonophagocytic assay titers to the initial dose of 7vPnC were significantly greater than those to the initial dose of PPV for 6 and 5 of 7 serotypes, respectively (P<.01 and P<.05, respectively). 7vPnC/7vPnC induced antibody responses that were similar to those after the first 7vPnC inoculation, and 7vPnC/PPV induced antibody responses that were similar to or greater than antibody responses after administration of PPV alone; PPV/7vPnC induced significantly lower antibacterial responses, compared with those induced by 7vPnC alone, for all serotypes (Pt;.05). Conclusion. In adults, an initial dose of 7vPnC is likely to elicit higher and potentially more effective levels of antipneumococcal antibodies than is PPV. In contrast with PPV, for which the induction of hyporesponsiveness was observed when used as a priming dose, 7vPnC elicits an immunological state that permits subsequent administration of 7vPnC or PPV to maintain functional antipolysaccharide antibody levels.
Graft failure represents a leading cause of mortality after organ transplantation. Acute late‐onset graft failure has not been widely reported. The authors describe the demographics, CT ...imaging–pathology findings, and treatment of patients presenting with the latter. A retrospective review was performed of lung transplant recipients at two large‐volume centers. Acute late‐onset graft failure was defined as sudden onset of bilateral infiltrates with an oxygenation index <200 without identifiable cause or concurrent extrapulmonary organ failure. Laboratory, bronchoalveolar lavage (BAL), radiology, and histology results were assessed. Between 2005 and 2016, 21 patients were identified. Median survival was 19 (IQR 13–36) days post onset. Twelve patients (57%) required intensive care support at onset, 12 (57%) required mechanical ventilation, and 6 (29%) were placed on extracorporeal life support. Blood and BAL analysis revealed elevated neutrophilia, with CT demonstrating diffuse ground‐glass opacities. Transbronchial biopsy samples revealed acute fibrinoid organizing pneumonia (AFOP), organizing pneumonia, and diffuse alveolar damage (DAD). Assessment of explanted lungs confirmed AFOP and DAD but also identified obliterative bronchiolitis. Patients surviving to discharge without redo transplantation (n = 2) subsequently developed restrictive allograft syndrome. This study describes acute late‐onset graft failure in lung allograft recipients, without known cause, which is associated with a dismal prognosis.
This multicenter study describes epidemiology, pathology, radiology, and treatment of acute late onset graft failure following lung transplantation.
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