Plasma and Cerebrospinal Fluid Population Pharmacokinetics of Vancomycin in Patients with External Ventricular Drain.

Vancomycin is a commonly used antibacterial agent in patients with primary central nervous system (CNS) infection. This study aims to examine predictors of vancomycin penetration into cerebrospinal fluid (CSF) in patients with external ventricular drainage and the feasibility of CSF sampling from the distal drainage port for therapeutic drug monitoring. Fourteen adult patients (9 with primary CNS infection) were treated with vancomycin intravenously. The vancomycin concentrations in blood and CSF (from proximal [CSF_P] and distal [CSF_D] drainage ports) were evaluated by population pharmacokinetics. Model-based simulations were conducted to compare various infusion modes. A three-compartment model with first-order elimination best described the vancomycin data. Estimated parameters included clearance (CL, 4.53 L/h), central compartment volume (Vc, 24.0 L), apparent CSF compartment volume (VCSF, 0.445 L), and clearance between central and CSF compartments (QCSF, 0.00322 L/h and 0.00135 L/h for patients with and without primary CNS infection, respectively). Creatinine clearance was a significant covariate on vancomycin CL. CSF protein was the primary covariate to explain the variability of QCSF. There was no detectable difference between the data for sampling from the proximal and the distal port. Intermittent infusion and continuous infusion with a loading dose reached the CSF target concentration faster than continuous infusion only. All infusion schedules reached similar CSF trough concentrations. Beyond adjusting doses according to renal function, starting treatment with a loading dose in patients with primary CSF infection is recommended. Occasionally, very high and possibly toxic doses would be required to achieve adequate CSF concentrations, which calls for more investigation of direct intraventricular administration of vancomycin. (This study has been registered at ClinicalTrials.gov under registration no. NCT04426383).

Ecological effects of selective oral decontamination on multidrug-resistance bacteria acquired in the intensive care unit: a case-control study over 5 years.

PURPOSE: This case-control study investigated the long-term evolution of multidrug-resistant bacteria (MDRB) over a 5-year period associated with the use of selective oropharyngeal decontamination (SOD) in the intensive care unit (ICU). In addition, effects on health care-associated infections and ICU mortality were analysed. METHODS: We investigated patients undergoing mechanical ventilation > 48 h in 11 adult ICUs located at 3 campuses of a university hospital. Administrative, clinical, and microbiological data which were routinely recorded electronically served as the basis. We analysed differences in the rates and incidence densities (ID, cases per 1000 patient-days) of MDRB associated with SOD use in all patients and stratified by patient origin (outpatient or inpatient). After propensity score matching, health-care infections and ICU mortality were compared. RESULTS: 5034 patients were eligible for the study. 1694 patients were not given SOD. There were no differences in the incidence density of MDRB when SOD was used, except for more vancomycin-resistant Enterococcus faecium (0.72/1000 days vs. 0.31/1000 days, p < 0.01), and fewer ESBL-producing Klebsiella pneumoniae (0.22/1000 days vs. 0.56/1000 days, p < 0.01). After propensity score matching, SOD was associated with lower incidence rates of ventilator-associated pneumonia and death in the ICU but not with ICU-acquired bacteremia or urinary tract infection. CONCLUSIONS: Comparisons of the ICU-acquired MDRB over a 5-year period revealed no differences in incidence density, except for lower rate of ESBL-producing Klebsiella pneumoniae and higher rate of vancomycin-resistant Enterococcus faecium with SOD. Incidence rates of ventilator-associated pneumonia and death in the ICU were lower in patients receiving SOD.

Anthropometric analysis of body habitus and outcomes in critically ill COVID-19 patients.

AIMS: This study aimed to determine whether anthropometric markers of thoracic skeletal muscle and abdominal visceral fat tissue correlate with outcome parameters in critically ill COVID-19 patients. METHODS: We retrospectively analysed thoracic CT-scans of 67 patients in four ICUs at a university hospital. Thoracic skeletal muscle (total cross-sectional area (CSA); pectoralis muscle area (PMA)) and abdominal visceral fat tissue (VAT) were quantified using a semi-automated method. Point-biserial-correlation-coefficient, Spearman-correlation-coefficient, Wilcoxon rank-sum test and logistic regression were used to assess the correlation and test for differences between anthropometric parameters and death, ventilator- and ICU-free days and initial inflammatory laboratory values. RESULTS: Deceased patients had lower CSA and PMA values, but higher VAT values (p < 0.001). Male patients with higher CSA values had more ventilator-free days (p = 0.047) and ICU-free days (p = 0.017). Higher VAT/CSA and VAT/PMA values were associated with higher mortality (p < 0.001), but were negatively correlated with ICU length of stay in female patients only (p < 0.016). There was no association between anthropometric parameters and initial inflammatory biomarker levels. Logistic regression revealed no significant independent predictor for death. CONCLUSION: Our study suggests that pathologic body composition assessed by planimetric measurements using thoracic CT-scans is associated with worse outcome in critically ill COVID-19 patients.

A Model-Based Approach to Assess Unstable Creatinine Clearance in Critically Ill Patients.

Creatinine clearance is an important tool to describe the renal elimination of drugs in pharmacokinetic (PK) evaluations and clinical practice. In critically ill patients, unstable kidney function invalidates the steady-state assumption underlying equations, such as Cockcroft-Gault. Although measured creatinine clearance (mCrCL) is often used in nonsteady-state situations, it assumes that observed data are error-free, neglecting frequently occurring errors in urine collection. In contrast, compartmental nonlinear mixed effects models of creatinine allow to describe dynamic changes in kidney function while explicitly accounting for a residual error associated with observations. Based on 530 serum and 373 urine creatinine observations from 138 critically ill patients, a one-compartment creatinine model with zero-order creatinine generation rate (CGR) and first-order CrCL was evaluated. An autoregressive approach for interoccasion variability provided a distinct model improvement compared to a classical approach (Δ Akaike information criterion (AIC) -49.0). Fat-free mass, plasma urea concentration, age, and liver transplantation were significantly related to CrCL, whereas weight and sex were linked to CGR. The model-based CrCL estimates were superior to standard approaches to estimate CrCL (or glomerular filtration rate) including Cockcroft-Gault, mCrCL, four-variable modification of diet in renal disease (MDRD), six-variable MDRD, and chronic kidney disease epidemiology collaboration as a covariate to describe cefepime and meropenem PKs in terms of objective function value. In conclusion, a dynamic model of creatinine kinetics provides the means to estimate actual CrCL despite dynamic changes in kidney function, and it can easily be incorporated into population PK evaluations.

Impact of pathologic body composition assessed by CT-based anthropometric measurements in adult patients with multiple trauma: a retrospective analysis.

PURPOSE: In recent years, there has been mounting evidence on the clinical importance of body composition, particularly obesity and sarcopenia, in various patient populations. However, the relevance of these pathologic conditions remains controversial, especially in the field of traumatology. Computed tomography-based measurements allow clinicians to gain a prompt and thorough assessment of fat and muscle compartments in trauma patients. Our aim was to investigate whether CT-based anthropometric parameters of fat and muscle tissues show correlations with key elements of pre-hospital and clinical care in an adult population with multiple trauma. METHODS: In this retrospective analysis we searched our institutional records of the German Trauma Registry (TraumaRegister DGU®) from January 2008 to May 2014. Included were 297 adult trauma patients with multiple trauma who underwent a whole-body CT-scan on admission and were treated in an ICU. We measured anthropometric determinants of abdominal core muscle and adipose tissue using the digital imaging software OsiriX™. Multivariate linear and logistic regression analyses were conducted to unveil potential correlations. RESULTS: None of the obesity-linked anthropometric parameters were associated with longer pre-hospital or initial ED treatment times. Obese patients were less frequently intubated at the site of the accident. Patients with increased abdominal fat tissue received on average lower volumes during fluid resuscitation in the pre-hospital phase but were not more often in shock on admission. During ED treatment, fluid resuscitation and transfusion volumes were not affected by abdominal fat tissue, although transfusion rates were higher in the obese. Furthermore, damage control surgeries took place less frequently in patients with increased abdominal fat tissue markers. Obesity parameters did not affect the prevalence of sepsis, although increased abdominal fat was associated with higher white blood cell counts on admission. Finally, there was no statistically significant correlation between sarcopenia or obesity markers and duration of mechanical ventilation, ICU length of stay or neurologic outcome. CONCLUSION: CT-based assessment of abdominal fat and muscle mass is a simple method in revealing pathologic body composition in trauma patients. Our study suggests that obesity influences pre-hospital and ED treatment and early immune response in multiple trauma. Nevertheless, we could not demonstrate any significant effect of abdominal fat and muscle tissue parameters on the course of treatment, in particular the duration of mechanical ventilation, ICU length of stay and neurologic outcome.

Longitudinal lung function measurements in single lung transplant recipients with chronic lung allograft dysfunction.

BACKGROUND: Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) recipients is challenging. The aim of this study was to assess the diagnostic and prognostic value of longitudinal lung function tests in SLTX recipients with CLAD. METHODS: A total of 295 SLTX recipients were analyzed and stratified according to native lung physiology. In addition to spirometry, measurements of static lung volumes and lung capacities were used to phenotype patients and to assess their prognostic value. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n = 71). RESULTS: Of 224 lung transplant recipients, 105 (46.9%) developed CLAD. Time to CLAD onset (hazard ratio [HR]: 0.82, 95% CI: 0.74-0.90; p < 0.001), severity of CLAD at onset (HR: 0.97, 95% CI: 0.94-0.99; p = 0.009), and progression after onset of CLAD (HR: 1.03, 95% CI: 1.00-1.05; p = 0.023) were associated with outcome. Phenotypes at onset were bronchiolitis obliterans syndrome (BOS) (59.1%), restrictive allograft syndrome (RAS) (12.4%), mixed phenotype (6.7%), and undefined phenotype (21.9%). Survival estimates differed significantly between phenotypes (p = 0.004), with RAS and mixed phenotype being associated with the worst survival, followed by BOS and undefined phenotype. Finally, a higher hazard for mortality was noticed for RAS (HR: 2.34, 95% CI: 0.99-5.52; p = 0.054) and mixed phenotype (HR: 3.30, 95% CI: 1.20-9.11; p = 0.021) while controlling for time to CLAD onset and severity of CLAD at onset. CONCLUSIONS: Phenotyping CLAD in SLTX remains challenging with a high number of patients with an undefined phenotype despite comprehensive lung function testing. However, phenotyping is of prognostic value. Furthermore, early, severe, and progressive CLADs are associated with worse survival.

Safety and Efficacy of Steroid Pulse Therapy for Acute Loss of FEV1 in Lung Transplant Recipients After Exclusion of Acute Cellular Rejection.

BACKGROUND: The standard treatment of acute cellular rejection after lung transplantation (LTx) is a high-dose steroid pulse therapy. In our center, this therapy is also the standard of care for LTx recipients with acute loss of forced expiratory volume in 1 second (FEV1), after excluding specific causes such as acute rejection on biopsy. The aim of this retrospective study was to evaluate the safety and efficacy of steroid pulse therapy. METHODS: From 2015 to 2018, 33 consecutive patients (17 male patients, mean age ± SD, 50.5 ± 12.5 years) were included. All patients underwent routine examinations to exclude acute cellular rejection and other specific causes. FEV1 was routinely measured after 5 days, and 1, 3, and 6 months. Positive response to steroid pulse therapy was defined by increase of FEV1 > 10%. RESULTS: The mean decrease ± SD from baseline in FEV1 at the start of steroid pulse therapy was 380 ± 630 mL (P = .02). FEV1 changed after 5 days by 170 ± 180 mL (P = .0007), and after 1 month by 140 ± 230 mL (P = .70), 3 months by -60 ± 240 mL (P = .15), and 6 months by -80 ± 290 mL (P = .73). A positive response was observed in 21% of patients after 3 months and 12% after 6 months. High bronchoalveolar lavage (BAL) eosinophil count correlated with a higher FEV1 after steroid pulse therapy. Serious complications were observed in 4 out of 33 patients (12%) with 1 fatal event (pneumonia). CONCLUSIONS: Only a minority of patients after LTx with loss of FEV1 after exclusion of acute cellular rejection benefit from steroid pulse therapy. Patients with BAL eosinophilia are more likely to respond. However, severe complications were observed.

Fournier´s Gangrene Under Sodium-Glucose Cotransporter 2 Inhibitor Therapy as a Life-Threatening Adverse Event: A Case Report and Review of the Literature.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a relatively new class of oral antidiabetic drugs. The US FDA has recently published a new warning about the safety of SGLT2 inhibitor administration in type 2 diabetes mellitus patients. There is an emerging evidence of an increased risk for developing Fournier´s gangrene (FG; a life-threatening complication) while under SGLT2 therapy. However, there are only three case reports and a total of 55 patients reported by the FDA to date. Therefore, there is a lack of evidence-based treatment algorithms for clinicians. We present the case of a 39-year-old male patient with diabetes on oral dapagliflozin, metformin, and sitagliptin therapy who was admitted with FG to our hospital. Following emergency scrotal surgery, he had to be transferred to the intensive care unit due to respiratory and circulatory insufficiency. After a prolonged 27-day hospital stay with delirium, blood glucose imbalance, and five further surgical interventions, the patient was stabilized and discharged. Dapagliflozin was discontinued permanently. This case demonstrates the risks of SGLT2 inhibitor therapy and the importance of early discontinuation after the occurrence of severe adverse events such as FG. According to the evidence in the literature, deranged glucose levels before admission are a common risk factor. However, further studies are required to identify patients at risks for FG and to investigate a direct connection with SGLT2 inhibitors.

Lung transplantation in patients with severe pulmonary hypertension-Focus on right ventricular remodelling.

OBJECTIVE: This study was meant to analyse the centre experience of the Munich Lung Transplant Group in lung transplantation of patients with severe pulmonary hypertension. Outcome data focus on survival and right heart remodelling. METHODS: All patients receiving a lung transplant between 10/2010 and 08/2016 were retrospectively analysed (n = 343). Patients were categorised into individuals with or without severe pre-operative pulmonary hypertension (PH; mPAP ≥ 35 mm Hg or mPAP ≥ 25 mm Hg with cardiac index < 2.0 L/min/m2 ). Among those, patients with severe PH secondary to lung disease (Nice Class III) were compared with patients with severe PH due to idiopathic PH (IPAH; Nice Class I). All surviving patients with severe PH were electively followed up by echocardiography. RESULTS: Kaplan-Meier survival probabilities after lung transplantation of each group according to pre-operative mPAP values showed no statistically significant difference (P = 0.14 by log-rank test). Lung transplantation in severe PH patients led to marked right ventricular remodelling as indicated by significantly increased tricuspid annular plane systolic excursion (TAPSE) (P = 0.002), decreased right ventricular end-diastolic dimensions (P = 0.001) and overall reduction in tricuspid valvular regurgitation, when compared to pre-operative assessments. CONCLUSION: Sequential bilateral lung transplantation (BLTx) in patients with severe pulmonary hypertension is a feasible treatment option in this high-risk group in experienced high-volume centres. Lung transplantation allows for resolution of secondary right heart failure in these patients.

Pirfenidone exerts beneficial effects in patients with IPF undergoing single lung transplantation.

Pirfenidone demonstrated pleiotropic antiinflammatory effects in various experimental and clinical settings. The aim of this study was to assess the impact of previous treatment with pirfenidone on short-term outcomes after single lung transplantation (SLTx). Therefore, patients with idiopathic pulmonary fibrosis (IPF) who were undergoing SLTx were screened retrospectively for previous use of pirfenidone and compared to respective controls. Baseline parameters and short-term outcomes were recorded and analyzed. In total, 17 patients with pirfenidone were compared with 26 patients without antifibrotic treatment. Baseline characteristics and severity of disease did not differ between groups. Use of pirfenidone did not increase blood loss, wound-healing, or anastomotic complications. Severity of primary graft dysfunction at 72 hours was less (0.3 ± 0.6 vs 1.4 ± 1.3, P = .002), and length of mechanical ventilation (37.5 ± 34.8 vs 118.5 ± 151.0 hours, P = .016) and intensive care unit (ICU) stay (6.6 ± 7.1 vs 15.6 ± 20.3, P = .089) were shorter in patients with pirfenidone treatment. An independent beneficial effect of pirfenidone was confirmed by regression analysis while controlling for confounding variables (P = .016). Finally, incidence of acute cellular rejections within the first 30 days after SLTx was lower in patients with previous pirfenidone treatment (0.0% vs 19.2%; P = .040). Our data suggest a beneficial role of previous use of pirfenidone in patients with IPF who were undergoing SLTx.

Effect of Intraoperative Single-Shot Application of Vancomycin in Liver Transplant Recipients on Postoperative Infections With Enterococcus faecium and Enterococcus faecalis.

OBJECTIVES: Infections are major causes of morbidity and mortality in the early postoperative period after liver transplant. We observed a high rate of enterococcal infections at our center. Therefore, we added an intraoperative single shot of vancomycin to the standard regimen of meropenem given over 5 days. The aim of this study was to determine the prevalence of both Enterococcus faecium and Enterococcus faecalis infections during the first 28 days after surgery depending on the type of antibiotic prophylaxis and their implications on mortality and morbidity. MATERIALS AND METHODS: Our retrospective cohort analysis included 179 patients: 93 patients received meropenem only and 86 patients were treated with meropenem plus vancomycin. RESULTS: During the first 28 days after transplant, microbiological tests showed that 51 patients (28.5%) were positive for Enterococcus faecium and 25 patients (14.0%) were positive for Enterococcus faecalis. Enterococcus faecium infections appeared significantly more often in patients without vancomycin (P = .013). In the second week after transplant, there was a significant reduction in Enterococcus faecium infections in the meropenem plus vancomycin group (P = .015). Enterococcus faecalis infections occurred more often in the patients receiving meropenem alone, but results were not statistically significant (P = .194). There was a trend toward more frequent renal replacement therapy in the meropenem plus vancomycin group. We found no differences between the groups regarding survival after 1 and 2 years, length of hospital stay, or duration in the intensive care unit. Overall 1-year survival was 78.8% (141/179 patients). CONCLUSIONS: Although postoperative Enterococcus species infections can be reduced after liver transplant by adding vancomycin to the intraoperative antibiotic regimen, it does not improve the long-term outcomes.

Quantification of Adipose Tissue and Muscle Mass Based on Computed Tomography Scans: Comparison of Eight Planimetric and Diametric Techniques Including a Step-By-Step Guide.

BACKGROUND: Recent scientific work proved that knowledge about body composition beyond the body mass index is essential. Both adipose tissue and muscular status are determining risk factors of morbidity and mortality. Analysis of single cross-sectional computed tomography (CT) images, acquired during routine care only to prevent additional radiation exposure, provide a detailed insight into the body composition of chronically and critically ill patients. METHODS: This retrospective study included 490 trauma patients of whom a whole-body multiple detector CT scan was acquired at admission. From a single cross-sectional CT, we compared eight diametric and planimetric techniques for the assessment of core muscle mass as well as visceral and subcutaneous adipose tissue. Furthermore, we derived formulas for converting the measurement results of various techniques into each other. RESULTS: For intra- and interobserver reliability, we obtained intraclass correlation coefficients (ICCs) ranging from 0.947 to 0.997 (intraobserver reliability) and from 0.850 to 0.998 (interobserver reliability) for planimetric measurements. Diametric techniques conferred lower ICCs with 0.851-0.995 and 0.833-0.971, respectively. Overall, area-based measurements of abdominal adipose tissue yielded highly correlated results with diametric measures of obesity. For example, the Pearson correlation of visceral adipose tissue and sagittal abdominal diameter was 0.87 for male and 0.82 for female patients. Planimetric and diametric muscle measurements correlated best for lean psoas area and bilateral diametric measurement of the psoas with a Pearson correlation of 0.90 and 0.93 for male and female patients, respectively. CONCLUSION: Planimetric measurements should remain the gold standard to describe fat and muscle compartments. Diametric measurements could however serve as a surrogate if planimetric techniques are not readily available or feasible as for example in large registries.

Intraoperative Anesthetic Management of Lung Transplantation: Center-Specific Practices and Geographic and Centers Size Differences.

OBJECTIVE: Although increasing evidence in lung transplantation (LTx) suggests that intraoperative management could influence outcomes, there are no guidelines available regarding intraoperative management of LTx. The overall goal of the study was to assess geographic and center volume-specific clinical practices in perioperative management. DESIGN: Prospective data analysis. SETTING: Online survey from a single-center university hospital. PARTICIPANTS: European and non-European LTx centers. INTERVENTIONS: An online survey was sent to 176 centers currently performing LTx procedures. It covered organizational data, general anesthesia considerations, fluid therapy and coagulation, antioxidant and anti-inflammatory therapies, and ventilation strategies. MEASUREMENTS AND MAIN RESULTS: The response rates were 57.5% (n = 42) from European and 32% (n = 33) from non-European countries. Significant differences between European and non-European countries were use of volatile hypnotics (p = 0.016), use of sufentanil (p < 0.001), inotropic agents (p = 0.001) and colloid infusion (p < 0.001), use of calibrated pulse contour analysis (p = 0.004), use of intraoperative traditional laboratory-based coagulation tests (p = 0.001) and platelet function analysis (p = 0.005), and use of higher peak inspiratory pressure (p = 0.009). Center volume-specific differences were use of fentanyl (p = 0.03) and the use of higher peak inspiratory pressure (p = 0.005) for ventilation. Induction of anesthesia and use of advanced hemodynamic monitoring, therapy for pulmonary hypertension, antioxidant and anti-inflammatory therapies, and ventilation strategies were not different among the centers. CONCLUSIONS: This survey demonstrated for the first time statistically significant differences among European and non-European centers and among low- versus high-volume centers regarding intraoperative management during LTx. These observations will be of some guidance for the LTx community and may trigger more extensive studies.

Temporary Intra-Operative Portocaval Shunts, Post-Operative Infections, and Mid-Term Survival after Cava-Sparing Liver Transplantation.

BACKGROUND: Temporary intra-operative portocaval shunts (TPCS) are believed to improve outcomes after cava-sparing liver transplantation. We hypothesize that decompression of the portal venous system via a TPCS reduces gut congestion, thereby decreasing bacterial translocation. Thus, we sought to clarify whether transplantation with a TPCS alters rates of post-operative infections and survival. PATIENTS AND METHODS: Patients undergoing liver transplantation (n = 189) were stratified by usage of a TPCS and the type of intra-operative antibiotic prophylaxis. Rates of post-operative infections were analyzed using the χ2 test. The log-rank test was used to compare 120-d survival. RESULTS: The analysis of patients transplanted with a TPCS and meropenem revealed increased infection rates with gut-specific pathogens (Escherichia coli, Escherichia faecalis, Escherichia faecium; p = 0.04) and equal 120-d survival in comparison with patients transplanted without a TPCS. When vancomycin was added to meropenem infection rates did not differ and patients transplanted with a TPCS had better survival in comparison with patients transplanted without a TPCS (p = 0.02). Within the TPCS group, the administration of meropenem and vancomycin was associated with improved survival in comparison with meropenem only (p = 0.03). CONCLUSION: Survival of patients may be improved by usage of a TPCS when gut-specific pathogens are covered by intra-operative antibiotic prophylaxis.

Outcome of lung transplantation in idiopathic pulmonary fibrosis with previous anti-fibrotic therapy.

BACKGROUND: Anti-fibrotic drugs may interfere with wound-healing after major surgery, theoretically preventing sufficient bronchial anastomosis formation after lung transplantation (LTx). The aim of this study was to assess the impact of previous treatment with pirfenidone and nintedanib on outcomes after LTx in patients with idiopathic pulmonary fibrosis (IPF). METHODS: All patients with IPF undergoing LTx at the University of Munich between January 2012 and November 2016 were retrospectively screened for previous use of anti-fibrotics. Post-transplant outcome and survival of patients with and without anti-fibrotic treatment were analyzed. RESULTS: A total of 62 patients with IPF were transplanted (lung allocation score [mean ± SD] 53.1 ± 16.1). Of these, 23 (37.1%) received pirfenidone and 7 (11.3%) received nintedanib before LTx; the remaining 32 (51.6%) did not receive any anti-fibrotic drug (control group). Patients receiving anti-fibrotics were significantly older (p = 0.004) and their carbon monoxide diffusion capacity was significantly higher (p = 0.008) than in controls. Previous anti-fibrotic treatment did not increase blood product utilization, wound-healing or anastomotic complications after LTx. Post-transplant surgical revisions due to bleeding and/or impaired wound-healing were necessary in 18 (29.0%) patients (pirfenidone 30.4%, nintedanib 14.3%, control 31.3%; p = 0.66). Anastomosis insufficiency occurred in 2 (3.2%) patients, both in the control group. No patient died within the first 30 days post-LTx, and no significant differences regarding survival were seen during the follow-up (12-month survival: pirfenidone 77.0%, nintedanib 100%, control 90.6%; p = 0.29). CONCLUSION: Our data show that previous use of anti-fibrotic therapy does not increase surgical complications or post-operative mortality after LTx.

Lung volumes predict survival in patients with chronic lung allograft dysfunction.

Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD.A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI 1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes.Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration.

Extracorporeal Circulation During Lung Transplantation Procedures: A Meta-Analysis.

Extracorporeal circulation (ECC) is an invaluable tool in lung transplantation (lutx). More than the past years, an increasing number of centers changed their standard for intraoperative ECC from cardiopulmonary bypass (CPB) to extracorporeal membrane oxygenation (ECMO) - with differing results. This meta-analysis reviews the existing evidence. An online literature research on Medline, Embase, and PubMed has been performed. Two persons independently judged the papers using the ACROBAT-NRSI tool of the Cochrane collaboration. Meta-analyses and meta-regressions were used to determine whether veno-arterial ECMO (VA-ECMO) resulted in better outcomes compared with CPB. Six papers - all observational studies without randomization - were included in the analysis. All were considered to have serious bias caused by heparinization as co-intervention. Forest plots showed a beneficial trend of ECMO regarding blood transfusions (packed red blood cells (RBCs) with an average mean difference of -0.46 units [95% CI = -3.72, 2.80], fresh-frozen plasma with an average mean difference of -0.65 units [95% CI = -1.56, 0.25], platelets with an average mean difference of -1.72 units [95% CI = -3.67, 0.23]). Duration of ventilator support with an average mean difference of -2.86 days [95% CI = -11.43, 5.71] and intensive care unit (ICU) length of stay with an average mean difference of -4.79 days [95% CI = -8.17, -1.41] were shorter in ECMO patients. Extracorporeal membrane oxygenation treatment tended to be superior regarding 3 month mortality (odds ratio = 0.46, 95% CI = 0.21-1.02) and 1 year mortality (odds ratio = 0.65, 95% CI = 0.37-1.13). However, only the ICU length of stay reached statistical significance. Meta-regression analyses showed that heterogeneity across studies (sex, year of ECMO implementation, and underlying disease) influenced differences. These data indicate a benefit of the intraoperative use of ECMO as compared with CPB during lung transplant procedures regarding short-term outcome (ICU stay). There was no statistically significant effect regarding blood transfusion needs or long-term outcome. The superiority of ECMO in lutx patients remains to be determined in larger multi-center randomized trials.

Long-term Results of Arthroscopic Arthrolysis for Arthrofibrosis After Anterior Cruciate Ligament Reconstruction.

PURPOSE: The current study was conducted to evaluate the long-term clinical and radiological outcomes after arthroscopic arthrolysis for arthrofibrosis after anterior cruciate ligament reconstruction (ACLR). METHODS: All patients treated with arthrolysis between 1990 and 1998 were included. Indication was arthrofibrosis in at least one knee compartment or a cyclops syndrome limiting range of motion (ROM) by > 5° of extension deficit and 15° of flexion deficit. International Knee Documentation Committee (IKDC) 2000 subjective and objective, Lysholm score, and x-ray evaluation were documented. Statistical analysis and power calculation were performed (P < .05). RESULTS: One hundred forty-one patients (follow-up, 71%) were examined at a mean of 18.7 ± 2.6 years after arthroscopic arthrolysis. Mean IKDC 2000 score was 79.49 ± 14.32. IKDC objective was normal in 0%, nearly normal in 6%, abnormal in 56%, and severely abnormal in 38%. One hundred percent of patients showed more than grade II osteoarthritis. ROM improvement after arthrolysis did not change significantly compared with midterm results (t = 4.5 years). Patients with persisting motion deficits (P = .02) and after medial meniscus resection (P < .001) at time of ACLR showed significantly greater progression of osteoarthritis in comparison with patients without these additional disorders. In case of arthrolysis later than 1 year after ACLR, a more severe osteoarthritis grade (4% vs 20% grade III; P = .038) and a lower jump distance (IKDC: 61% A, 25% B vs 39% A, 41% B; P = .028) were obvious compared with patients who underwent arthrolysis within the first year after ACLR. CONCLUSIONS: Long-term motion improvement can be achieved by arthrolysis. Persistent loss of motion resulted in a higher degree of osteoarthritis in the study population. Early intervention seems advisable as patients with arthrolysis later than 1 year after index surgery reached worse IKDC objective grading. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Core Muscle Size Predicts Postoperative Outcome in Lung Transplant Candidates.

BACKGROUND: Careful patient selection is the prerequisite to raise transplant benefit. In lung transplant (LT) candidates, the effect of body mass index (BMI) on postoperative outcome remains controversial, possibly due to the inaccuracy of BMI in discriminating between fat and muscle mass. We therefore hypothesized that assessment of body composition by muscle mass measures is more accurate than by BMI regarding postoperative outcome. METHODS: All LT recipients from 2011 to 2014 were included and retrospectively analyzed. Lean psoas area (LPA) was assessed from pretransplant computed tomography scans, and associations with postoperative outcomes were investigated. RESULTS: Included were 103 consecutive LT recipients with a mean pre-LT BMI of 22.0 ± 4.0 kg/m(2) and a mean LPA of 22.3 ± 8.3 cm(2). LPA was inversely associated with length of mechanical ventilation (p = 0.03), requirement of tracheostomy (p = 0.035), and length of stay in the intensive care unit (p = 0.02), while controlling for underlying disease, BMI, sex, age, and procedure; in contrast, BMI was not (p = 0.25, p = 0.54, and p = 0.42, respectively.). Multiple regression analysis revealed that the 6-minute walk distance at the end of pulmonary rehabilitation was significantly associated with LPA (p = 0.02). CONCLUSIONS: LPA can easily be assessed in LT candidates as part of pretransplant evaluation and was significantly associated with short-term outcome, whereas BMI was not. Assessment of LPA may provide additional information on body composition beyond BMI. However, the clinical utility has to be further evaluated.