Optimal Timing of Pulmonary Banding for Newborns with Single Ventricle Physiology and Unrestricted Pulmonary Blood Flow.

The aim of this study was to determine the optimal timing of pulmonary artery band (PAB) placement in neonates with single ventricle physiology, unrestricted pulmonary blood flow, and no systemic outflow tract obstruction. Retrospective chart review of all patients who underwent isolated PAB for single ventricle physiology between January 2005 and December 2014 was carried out. The influence of age at the time of PAB on operative mortality, the need for reoperation to adjust the PAB, the preparedness of the pulmonary vascular bed prior to the second-stage bidirectional cavopulmonary shunt (BCPS), and the outcomes following BCPS were studied. The study cohort included 54 subjects (34 males). The median age at the time of PAB was 18 days. The overall mortality following PAB was 4 % (2/54). Reoperation for PAB adjustment was 7 % (4/54). Younger age at the time of PAB was not associated with mortality or increased risk of reoperation. There was a mild positive correlation between the age at PAB and the mean pulmonary artery pressure prior to BCPS. There was also a weak positive correlation between the age at PAB and the duration of ventilation following BCPS. Age at the time of PAB did not influence pulmonary vascular resistance (PVR) prior to BCPS or the mortality and hospital stay following BCPS. PAB can be done safely and effectively soon after birth in neonates with single ventricle physiology, increased pulmonary blood flow, and no potential or actual systemic outflow tract obstruction. It may not be necessary to wait for a few weeks after birth for the neonatal PVR to fall before placing a PAB.

Negative pressure wound therapy for sternal wound infections following congenital heart surgery.

OBJECTIVE: This study examines the efficacy of a comprehensive, multidisciplinary wound management team and negative pressure wound therapy (NPWT) for the treatment of sternal wound infections in congenital heart surgery patients. METHOD: A single-institution retrospective review of all congenital heart surgery patients with post-operative sternal wound infections who were treated with NPWT was performed. Patients were evaluated based on (a) whether NPWT occurred before or after the establishment of a multidisciplinary wound management team, and (b) whether NPWT was initiated early (within 2 days) or late (greater than 2 days) after diagnosis of a sternal wound infection. RESULTS: The median duration of NPWT was 12 days (range 2-50 days). NPWT was successfully initiated in patients as young as 15 days of age. There was a trend toward shorter duration of both NPWT and antibiotic use following (a) the implementation of the multidisciplinary wound management team, and (b) in patients with early use of NPWT; however, these results did not achieve statistical significance. CONCLUSION: NPWT can be successfully utilised in congenital heart surgery patients, including young neonates, for the treatment of sternal wound infections. The trends observed in the reduction of wound therapy duration and antibiotic duration with early implementation of negative pressure therapy and multidisciplinary wound management require further investigation to verify their clinical efficacy in patient care.

Characterization of HCV-specific CD4+Th17 immunity in recurrent hepatitis C-induced liver allograft fibrosis.

Hepatitis C virus (HCV) recurrence with accelerated fibrosis following orthotopic liver transplantation (OLT) is a universal phenomenon. To evaluate mechanisms contributing to HCV induced allograft fibrosis/cirrhosis, we investigated HCV-specific CD4+Th17 cells and their induction in OLT recipients with recurrence utilizing 51 HCV+ OLT recipients, 15 healthy controls and 9 HCV- OLT recipients. Frequency of HCV specific CD4+ Tcells secreting IFN-γ, IL-17 and IL-10 was analyzed by ELISpot. Serum cytokines and chemokines were analyzed by LUMINEX. Recipients with recurrent HCV induced allograft inflammation and fibrosis/cirrhosis demonstrated a significant increase in frequency of HCV specific CD4+Th17 cells. Increased pro-inflammatory mediators (IL-17, IL-1ß, IL-6, IL-8 and MCP-1), decreased IFN-γ, and increased IL-4, IL-5 and IL-10 levels were identified. OLT recipients with allograft inflammation and fibrosis/cirrhosis demonstrated increased frequency of Foxp3+ regulatory T cells (Tregs) that inhibited HCV specific CD4+Th1 but not Th17 cells. This suggests that recurrent HCV infection in OLT recipients induces an inflammatory milieu characterized by increased IL-6, IL-1ß and decreased IFN-γ which facilitates induction of HCV specific CD4+Th17 cells. These cells are resistant to suppression by Tregs and may mediate an inflammatory cascade leading to cirrhosis in OLT recipients following HCV recurrence.

Impact of donor and recipient factors on allograft survival in lung transplantation: A single-center analysis.

BACKGROUND: It remains unclear which donor and recipient factors influence long-term allograft function in lung transplantation (LTx). METHODS: From October 1988 to February 2005, a total of 280 recipients underwent LTx at our center. Donor data and cause of death (CoD) were analyzed. The CoD was categorized according to rate of increase in intracranial pressure at the time of death. Each donor and recipient factor was correlated with long-term graft function. Recipient details, type of transplant, indication for transplant, and time on waiting list were analyzed. Recipients were stratified based on allograft ischemia time (AIT): 0 to 6, 6 to 8, 8 to 10, and >10 hours. RESULTS: Mean donor age was 30.9 years (36.7% male); 49.8% were cytomegalovirus (CMV) positive. Donor CoD was characterized by a slow rise in intracranial pressure (ICP) in 34.4%, rapid ICP in 18.7%, an intermediate ICP in 44.3%, and with no rise in 2.6%. A graft survival benefit was seen with female donors (P = .048); 34.4% of recipients ultimately developed graft failure at long term follow-up. Mean recipient age was 48 years; 63% were male and mean body-mass index (BMI) was 23.6; 60.2% had single lung transplantation, and mean wait list time was 323 days. Mean AIT totaled 421 minutes. Graft survival was longer with AIT of 8 to 10 hours compared to 6 to 8 hours (P = .03). CONCLUSIONS: Donor factor analysis implied only female donor status conferred a long-term graft survival advantage. Intracranial pressure rise differences appear clinically unimportant. Prolonged cold ischemic time (>10 hours) or low recipient BMI did not adversely affect allograft function in our review.

Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation.

BACKGROUND: A scoring system was recently proposed to grade the severity of primary graft dysfunction (PGD), a frequent early complication of lung transplantation. The purposes of this study are to: (1) validate the PGD grading system with respect to patient outcomes; and (2) compare the performance of criteria employing the arterial oxygenation to fraction of inspired oxygen (P/F) ratio to an alternative grading system employing the oxygenation index (OI). METHODS: We retrospectively reviewed the medical records of 402 patients having undergone lung transplantation at our institution from 1992 through 2004. The ISHLT PGD grading system was modified and grades were assigned up to 48 hours post-transplantation as follows: Grade 1 PGD, P/F > 300; Grade 2, P/F 200 to 300; and Grade 3, P/F < 200. A worst score T(0-48) was also assigned, which reflects the highest grade recorded between T0 and T48. RESULTS: The prevalence of severe PGD (P/F Grade 3) declined after transplant, from 25% at T0 to 15% at T48. Grouping patients by P/F grade at T48 demonstrated the clearest differentiation of 90-day death rates (Grade 1, 7%; Grade 2, 12%; Grade 3, 33%) (p = 0.0001). T48 OI grade also differentiates 90-day death rates. There was no difference in longer-term survival between patients with PGD Grades 1 and 2. OI grade at T0 qualitatively improved differential mortality between Grades 1 and 2; however, the differences did not reach statistical significance. Patients with a worst score T(0-48) of Grade 3 PGD did have significantly decreased long-term survival, as well as longer ICU and hospital stay, when compared with Grades 1 and 2 PGD. Significant risk factors for short- and long-term mortality in our multivariate model were P/F Grade 3 [worst score T(0-48) as well as T0 grade], single-lung transplant, use of cardiopulmonary bypass and high pre-operative mean pulmonary artery pressure. CONCLUSIONS: There is an increased risk of short- and long-term mortality and length of hospital stay associated with severe (Grade 3) PGD. The proposed ISHLT grading system can rapidly identify patients with poor outcomes who may benefit from early, aggressive treatment. Refinement of the scoring system may further improve patient risk stratification.

Fungal infections in transplant recipients receiving alemtuzumab.

Recently, we have used an anti-T-cell agent, alemtuzumab, as induction or conversion therapy to achieve a calcineurin (CNI) and steroid-free immunosuppressive regimen. We identified recipients who developed systemic fungal infections after the initiation of alemtuzumab and looked at their outcomes. The study population consisted of all pancreas transplant recipients who received alemtuzumab. Only invasive fungal infections were included in the analysis (eg, fungemia, meningitis, or pneumonia; fungal urinary tract infections were excluded). The organism was confirmed by culture, histopathology, or latex antigen test. Between February 2003 and February 2004, a total of 121 pancreas transplant recipients received alemtuzumab-56 as part of induction, and 65 as part of conversion. Of these, 8 (6.6%) developed an invasive fungal infection; 2 (3.6%) recipients as part of induction therapy and 6 (9.2%) as part of conversion therapy. Mean recipient age was 42.1 years. The mean length of time from alemtuzumab administration (first dose) to the diagnosis of the fungal infection was 115.9 days (range 5 to 318). The organisms identified initially were: Cryptococcus, Histoplasma, Aspergillus, and Candida. Overall, 3 (38%) of the eight patients died during ongoing treatment of their fungal infection: two from sepsis, one due to myocardial infarction. The other five recipients were treated successfully and have functioning grafts. The initial therapeutic agents used included: amphotericin B/liposomal AMB (n = 6), voriconazole (n = 3), capsofungin (n = 2), and fluconazole (n = 1). The use of alemtuzumab as induction or conversion therapy in pancreas transplant recipients may predispose patients to the development of systemic fungal infections. It would be important to determine what the most appropriate prophylaxis regimen would be for these patients.

Postfailure compressive behavior of tibial trabecular bone in three anatomic directions.

To obtain information describing the postfailure behavior of human proximal tibial trabecular bone, cube specimens of bone were mechanically tested in compression beyond the point of failure. Tests were performed in the three anatomic directions, plots of stress versus strain were obtained, and measures to describe the stress-strain relations before, during, and after failure were defined. These measures included elastic modulus, strength, postfailure slope, strain during maximum stress, and first postfailure minimum stress. For each anatomic direction, analyses were performed to correlate these parameters with ash density. Each of these measures was significantly correlated with ash density at the p < 0.05 level for all test directions, except for postfailure slope, which was correlated in the mediolateral and superior-inferior directions, and strain during maximum stress, which was correlated only in the superior-inferior direction. The data from this study enable trilinear stress-strain relations to be estimated for proximal tibial trabecular bone of various densities, and can serve as a first step toward modeling the behavior of trabecular bone before, during, and after failure.