C. Fegbeutel

Biological materials in chest wall reconstruction: initial experience with the Peri-Guard Repair Patch.

OBJECTIVE This study analyses the efficacy of the bovine Peri-Guard Repair Patch for chest wall reconstruction. METHODS Nine consecutive patients (seven males, median age: 61 years) underwent chest wall repair due to either secondary incisional herniation development after lung transplantation (LTX, n=3 patients) or malignant disease with chest wall infiltration. In all cases, repair was performed with a Peri-Guard Repair Patch (Synovis, St. Paul, MN, USA). At follow-up (4+/-2 months), quality of life, signs of re-herniation and incorporation of mesh (radiograph, blood samples and ultrasound) were assessed. RESULTS In all patients, a successful chest wall repair could be achieved and no signs of re-herniation were found. Oncologic patients with a diagnosis of desmoid tumour, primary histiocytosis of ribs, sarcoma or lung cancers were accessed through posterolateral thoracotomy and received a resection of two to four ribs. Post-LTX repair was performed by anterior mini-thoracotomy without rib resection. At follow-up, 80% of the patients presented with totally regained quality of life, with no signs of local infection, altered white blood cell (WBC) counts or elevated C-reactive protein (CRP) levels. On chest X-ray, only one patient showed areas of patch calcification, while all others were unremarkable. Chest ultrasound imaging confirmed the absence of adhesions, haematoma or seroma. In all cases, normal expansion and respiratory movement of the underlying lung were observed. CONCLUSIONS To achieve satisfactory results after chest wall reconstruction, a material with high-tensile strength, preferably soft structure, availability, ease of use and high biocompatibility is required. Especially in immunosuppressed patients, the biological Peri-Guard Repair Patch might be superior to the use of an artificial material.

Intentional ABO‐Incompatible Lung Transplantation

We report on a case of intentional blood group incompatible lung transplantation. A blood group O cystic fibrosis patient was mechanically ventilated and put on interventional lung assist for severe respiratory decompensation. Since timely allocation of a blood group O donor lung was impossible, an AB deceased donor lung rescue allocation was accepted and the transplant performed using a pre‐, peri‐ and postoperative antibody depletion protocol including plasmapheresis, ivIg administration, rituximab and immunoadsorption. Nine months after the transplant the patient is at home and well.

Juvenile hemochromatosis due to homozygosity for the G320V mutation in the HJV gene with fatal outcome.

To the Editor : Juvenile hemochromatosis (JH, MIM 602390) is a rare autosomal-recessive iron overload disorder with earlier onset and faster progression compared to the adult form of hemochromatosis (HH, MIM 235200), which is caused by mutations in HFE. Hypogonadism, liver disease, and an early development of cardiomyopathy are the main manifestations (1). JH is subdivided into two forms, designated as HFE2A and HFE2B, which are caused by mutations in the genes encoding hemojuvelin (HJV ; MIM 608374) and hepcidin antimicrobial peptide (HAMP ; MIM 606464), respectively (2, 3). In recent studies, HAMP and HJV have been proposed as potential modulators in hemochromatosis (4, 5). Additionally, there is evidence that digenic inheritance of HFE and HAMP can lead to iron overload (5, 6). Here, we report a complex genotype found in a JH-patient who was transferred to our centre in severe cardiogenic shock of unclear origin. Out of unremarkable history, this 21-year-old male patient was initially resuscitated due to sudden onset of ventricular fibrillation. After unremarkable coronary angiography and electrophysical examination, an intracardial defibrillator was implanted. Nine months later, the patient was readmitted due to abdominal symptoms and ascites. Furthermore he developed atrial fibrillation, which was not convertible. He was transferred to our centre with severe cardiac arrhythmias and cardiogenic shock due to global heart insufficiency. Stabilization could be achieved with the support of an arteriovenous ECMO (extracorporeal membrane oxygenator). Five days later, the ECMO was explanted and replaced by biventricular assist devices. For the left heart support, a long-term axial flow device was implanted (Heartmate II, Thoratec, Pleasanton, CA) and a short-term device was used for the right heart (Levitronix centrimag, Waltham, MA). The temporary right heart device was weaned and explanted 5 days later. The histopathological examination of the myocardial biopsy resulted in the presumptive diagnosis of hemochromatosis because of excessive iron storage and hypertrophy of myocardial tissue. Analysis of serum iron parameters confirmed the presumptive histopathological diagnosis (Table 1). Within the following 2 weeks, the patient developed progressive right heart failure, which was not treatable, and he died due to low cardiac output and multiorgan failure. The latest iron level was 94 umol/l, and the final ferritin concentration was 154,066 ug/l (shortly before death; it was 12,704 ug/l and 6403 ug/l 1 and 2 days before, respectively). The very high increase of ferritin concentrations at the last 2 days may reflect a release of ferritin from damaged cells rather than iron storage. The diagnosis of JH was genetically confirmed by the identification of homozygosity for G320V in HJV exon 4 (Table 1). Additionally, heterozygosity for H63D and S65C and homozygosity for IVS2+4T> C were detected in the HFE gene. In the HAMP gene, no sequence change was found. For each of the three genes, sequencing reactions for the coding exons and the flanking intronic sequences were performed. In HFE -related hemochromatosis, H63D and S65C are deemed to be risk factors (1) and the sequence change IVS2+4T>C is interpreted as a pathologically not relevant polymorphism (7, 8). We hypothesize that modulating effects of the identified HFE variants – in addition to homozygosity for the causative G320V mutation – may explain the clinical progression of the disease in this JH-patient. There is evidence that digenic inheritance of HFE and HAMP can lead to iron overload (5, 6), and modifying effects are assumed for HJV and HAMP in C282Y homozygous HFE patients, who showed a more symptomatic phenotype (4, 5). The contrary situation, i.e. a causative

Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.

This single‐center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82–21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42–31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86–16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98–12.81], p = 0.001), among others. Overall 1‐year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long‐term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40–5.25], p < 0.001), post‐LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06–5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39–2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in‐hospital mortality, outcomes among patients surviving to hospital discharge were unaffected.

Right-Sided Heart Failure and Extracorporeal Life Support in Patients Undergoing Pericardiectomy for Constrictive Pericarditis: A Risk Factor Analysis for Adverse Outcome

Background Right ventricular failure is a life‐threatening postoperative complication after pericardiectomy. We conducted a retrospective study with a special emphasis on right ventricular failure. Methods Between June 1997 and September 2011, 69 patients underwent surgical pericardiectomy at our center. Mean age was 59 (± 15.5) years, and 49 (71%) patients were male. Causes of constrictive pericarditis included idiopathic (52%, n = 36), tuberculosis (9%, n = 6), postcardiotomy (12%, n = 8), radiation (4%, n = 3), renal insufficiency (12%, n = 8), and autoimmune disease (12%, n = 8). Concomitant cardiac surgery was performed in 33 (48%) patients. Results In‐hospital mortality rate was 14% (10/69 patients). Extracorporeal membrane oxygenation (ECMO) was necessary in 8 (12%) cases because of right (n = 7) or biventricular (n = 1) failure. Statistical analysis showed a significant correlation between early mortality and the following preoperative variables: postcardiotomy (p = 0.049), radiation (p = 0.009), pleural effusion (p = 0.012), ascites (p = 0.039), hepatic congestion (p = 0.023), absence of calcification on X‐ray (p = 0.041), tricuspid valve insufficiency (TI, p < 0.001), and low cardiac index (p = 0.003). Diuretic usage (p = 0.044), peripheral edema (p = 0.050), low voltage (p = 0.027), dip‐plateau sign (p = 0.027), elevated GGT (p < 0.001), and decreased serum protein (p < 0.001) correlated with ECMO implantation. Binary logistic regression identified pleural effusion (OR = 16.2, 95% CI = 1.4‐191.5), moderate/severe TI (OR = 28.8, 95% CI = 2.7‐306.8) and low cardiac index (OR = 25.3, 95% CI = 2.0‐315.6) as preoperative independent risk factors for early mortality, whereas elevated GGT (OR = 28.3, 95% CI = 2.4‐329.2) and decreased protein (OR = 24.7, 95% CI = 1.8‐343.7) could predict right ventricular failure with the need for ECMO. Conclusion We recommend nondelayed ECMO support in case of significant postoperative right‐sided heart failure. High‐risk patients might benefit from elective pre‐ or intraoperative ECMO implantation.

Voriconazole and squamous cell carcinoma after lung transplantation: A multicenter study

This study evaluated the independent contribution of voriconazole to the development of squamous cell carcinoma (SCC) in lung transplant recipients, by attempting to account for important confounding factors, particularly immunosuppression. This international, multicenter, retrospective, cohort study included adult patients who underwent lung transplantation during 2005‐2008. Cox regression analysis was used to assess the effects of voriconazole and other azoles, analyzed as time‐dependent variables, on the risk of developing biopsy‐confirmed SCC. Nine hundred lung transplant recipients were included. Median follow‐up time from transplantation to end of follow‐up was 3.51 years. In a Cox regression model, exposure to voriconazole alone (adjusted hazard ratio 2.39, 95% confidence interval 1.31‐4.37) and exposure to voriconazole and other azole(s) (adjusted hazard ratio 3.45, 95% confidence interval 1.07‐11.06) were associated with SCC compared with those unexposed after controlling for important confounders including immunosuppressants. Exposure to voriconazole was associated with increased risk of SCC of the skin in lung transplant recipients. Residual confounding could not be ruled out because of the use of proxy variables to control for some confounders. Benefits of voriconazole use when prescribed to lung transplant recipients should be carefully weighed versus the potential risk of SCC.
EU PAS registration number: EUPAS5269.

Liver stiffness measurements and short-term survival after left ventricular assist device implantation: A pilot study.

BACKGROUND Hepatic dysfunction can contribute to the clinical outcome of patients with end-stage chronic heart failure (HF). This pilot study evaluated the importance of liver stiffness (LS) measurements by acoustic radiation force impulse (ARFI) imaging elastography in patients with end-stage chronic HF who underwent left ventricular assist device (LVAD) implantation. METHODS The study enrolled 28 patients (23 men), mean age of 54 ± 11 years, with end-stage chronic HF selected for LVAD implantation. At baseline, all patients received LS measurements using ARFI elastography. Hepatic venous pressure gradient measurements and transjugular liver biopsies were performed in 16 patients. Liver stiffness was measured 21 days (Follow-up 1, n = 23) and 485 ± 136 days (Follow-up 2, n = 13) after LVAD implantation. Patients were classified according to their baseline LS into Group I (low baseline LS [no significant fibrosis = Metavir F < 2]) or Group II (high baseline LS [significant fibrosis = Metavir F ≥ 2]). RESULTS LS at baseline was higher in Group II than in Group I (p < 0.001) and decreased significantly after LVAD implantation (Follow-up 1, p = 0.002; Follow-up 2, p = 0.002). Baseline LS correlated with liver fibrosis (p = 0.049) and central venous pressure (p = 0.001). Non-survivors showed higher LS (p = 0.019), bilirubin (p = 0.018), Model for End-Stage Liver Disease score (p = 0.001), and liver fibrosis (p = 0.004) compared with the survivors. In the univariate analysis, LS was a significant factor (p = 0.017) in predicting survival after LVAD implantation. CONCLUSIONS ARFI elastography shows that LS is influenced by central venous congestion and histologic changes of the liver in patients with end-stage chronic HF. LS may predict the outcome in patients after LVAD implantation.

Viremia after lung transplant: a cohort study on risk factors and symptoms associated with detection of Epstein-Barr virus

Background The frequency and impact of detection of Epstein-Barr virus in the blood of lung and heart-lung transplant recipients in the postoperative period is poorly characterized. Objective To investigate the frequency of virus detection, associated clinical symptoms and risk factors, and influence of virus detection on outcome. Methods A cohort of 98 lung transplant recipients were monitored for Epstein-Barr virus in blood before transplant and during their posttransplant hospital stay (median 4 weeks, range 1–21 weeks). Patients were followed up for retransplant or death for a median of 17 months. Results Epstein-Barr virus DNA was detected in 15 recipients (18.1%) before and in 39 recipients (41.5%) after transplant. Median viral load after transplant was 2300 copies per milliliter of blood (range, 900–45 000 copies/mL). Detection of Epstein-Barr virus DNA before transplant and mechanical ventilation before transplant were associated with detection of Epstein-Barr virus DNA after transplant. Shortness of breath, fatigue, and hoarseness were associated with detection of viral DNA after transplant. The incidence of retransplant or death was not increased in recipients who had viral DNA detected in their blood. Conclusions Epstein-Barr virus DNA in the blood before transplant and mechanical ventilation before transplant were associated with detection of viral DNA after transplant. Detection of viral DNA after transplant was frequent and clinically relevant.