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).

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.

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.

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.

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.

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.

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.

Evaluation of Short-Term Outcome after Lung Transplantation in the Lung Allocation Score Era.

BACKGROUND: In December 2011, the Eurotransplant Foundation (Leiden, The Netherlands) changed the allocation system for donor lungs from a model based on urgency and waiting time to the lung allocation score (LAS). OBJECTIVE: The aim of the study was to investigate the effects of the LAS implementation on the early outcome after lung transplantation in Germany. METHODS: We therefore retrospectively studied the outcome of the last 50 patients transplanted before and the first 50 patients transplanted after LAS implementation. RESULTS: Both patient groups were comparable in baseline characteristics at the time of transplantation. Postoperative hospital stays were comparable between the groups, that is, 40.3 ± 26.8 and 40.3 ± 31.3 days (p = 0.992). Also, survival rates on intensive care, during entire hospital stay, at 90 days, 6 month, and 1 year after transplant were comparable between the groups. The retrospectively calculated LASs of the patients transplanted under the old allocation system were not statistically significantly different from those after LAS implementation, that is, 46.5 ± 14.2 and 51.2 ± 17.4 (p = 0.139). CONCLUSION: We demonstrate, for the first time, that implementation of the LAS in Germany had no negative effect on the early outcome after lung transplantation. Our data indicate that patients transplanted before implementation of the LAS had a similar prospective transplant benefit.

Longitudinal mode competition and mode clustering in (Al,In)GaN laser diodes.

Longitudinal mode competition in (Al,In)GaN laser diodes at λ = 445nm and 515 nm with mode competition frequencies from 10 MHz to 150 MHz is observed. Up to two dozen lasing modes oscillate with the lasing mode rolling from the short wavelength edge to the long wavelength edge of the gain profile. The experimental results can be described very well with a set of multi-mode rate equations including self-, symmetric and asymmetric cross gain saturation. By tuning essential parameters of the gain saturation terms, mode competition disappears and single mode operation as well as mode clustering is found. This proves that the mechanisms of gain saturation have not only a profound impact on the complex temporal-spectral behavior but also explains mode clustering in (Al,In)GaN laser diodes, both in pulsed and continuous wave (cw) operation as a natural nonlinear effect without the necessity to add noise.

Variability of linezolid concentrations after standard dosing in critically ill patients: a prospective observational study.

INTRODUCTION: Severe infections in intensive care patients show high morbidity and mortality rates. Linezolid is an antimicrobial drug frequently used in critically ill patients. Recent data indicates that there might be high variability of linezolid serum concentrations in intensive care patients receiving standard doses. This study was aimed to evaluate whether standard dosing of linezolid leads to therapeutic serum concentrations in critically ill patients. METHODS: In this prospective observational study, 30 critically ill adult patients with suspected infections received standard dosing of 600 mg linezolid intravenously twice a day. Over 4 days, multiple serum samples were obtained from each patient, in order to determine the linezolid concentrations by liquid chromatography tandem mass spectrometry. RESULTS: A high variability of serum linezolid concentrations was observed (range of area under the linezolid concentration time curve over 24 hours (AUC24) 50.1 to 453.9 mg/L, median 143.3 mg*h/L; range of trough concentrations (Cmin) < 0.13 to 14.49 mg/L, median 2.06 mg/L). Furthermore, potentially subtherapeutic linezolid concentrations over 24 hours and at single time points (defined according to the literature as AUC24 < 200 mg*h/L and Cmin < 2 mg/L) were observed for 63% and 50% of the patients, respectively. Finally, potentially toxic levels (defined as AUC24 > 400 mg*h/L and Cmin > 10 mg/L) were observed for 7 of the patients. CONCLUSIONS: A high variability of linezolid serum concentrations with a substantial percentage of potentially subtherapeutic levels was observed in intensive care patients. The findings suggest that therapeutic drug monitoring of linezolid might be helpful for adequate dosing of linezolid in critically ill patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT01793012. Registered 24 January 2013.

Munich lung transplant group: waiting list during the first 9 months of the lung allocation score era.

OBJECTIVE AND METHODS: The Eurotransplant Foundation introduced the lung allocation score (LAS) in Germany on December 10, 2011. We analyzed characteristics of the Munich Lung Transplant Group (MLTG) waiting list during the first 9 months after the introduction of the LAS. RESULTS: A mean number of 39 ± 1 patients were constantly listed for lung transplantation and 60 transplants were performed by the MLTG during the observation period. While the majority (42 ± 0%) of patients waiting for transplant comprised chronic obstructive pulmonary disease (COPD)/emphysema patients, only 26% of transplanted patients suffered from COPD/emphysema. Instead, the majority (42%) of transplanted patients suffered from interstitial lung disease. Waiting times did not markedly change in the LAS era. Notably, patients with interstitial lung disease had shorter waiting times when compared with patients suffering from COPD/emphysema and cystic fibrosis, both on the waiting list and at the time of transplant. CONCLUSION: The MLTG lung transplant waiting list has not markedly changed during the first 9 months after the introduction of the LAS. Our data indicate that the LAS accommodates disease-specific patient statuses well. Although patients with interstitial lung disease are preferably transplanted, the LAS system provides a very reasonable basis to also list and transplant COPD/emphysema patients.

Parameters associated with short- and midterm survival in bridging to lung transplantation with extracorporeal membrane oxygenation.

Patients with terminal lung failure may be bridged to lung transplantation (LTX) by extracorporeal membrane oxygenation (ECMO). With the present shortage of donor organs and the high level of invasiveness of ECMO treatment, appropriate selection criteria for bridge to transplant need to be defined. We report retrospective data from 26 patients on ECMO listed for LTX. Seven patients were successfully transplanted (LTX-s). Six patients survived until transplantation, but died intra- or post-operatively (LTX-ns). Thirteen patients died before transplantation (Fail). There was no difference between LTX-s and the 19 overall non-survivors (NS) prior to ECMO initiation with regard to demographic data or ventilator parameters except for higher PaO2 /FiO2 in the LTX-s. Time on ECMO pre-LTX did not differ in the LTX-s and LTX-ns groups. SOFA score was lower in LTX-s when compared to LTX-ns before ECMO (p = 0.0155), during bridging (p = 0.028), and right before transplantation (p = 0.0038). Maximal bilirubin during bridging and bilirubin prior to transplantation was markedly elevated in the LTX-ns group [4.2 (2.4-4.7) vs. 1.1 (0.8-2.0) mg/dL; p = 0.0266 and 1.6 (1.2-3.0) vs. 0.5 (0.5-0.5) mg/dL; p = 0.0047). Bridging to LTX is a challenging but viable option for selected patients. Special consideration should be given to hepatic function.

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.

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.

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.

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.

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.