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Background--We recently demonstrated that a targeted psychological intervention has quality of life, mood, and social intimacy benefits for patients awaiting lung transplantation. Objective--To evaluate the impact of the patient's participation in treatment on caregiver functioning. Design and Intervention--Caregivers of patients participating in a randomized clinical trial designed to compare 2 telephone-based psychological interventions completed outcome measures at baseline and at 1 and 3 months after patients completed treatment. Patients were randomized to receive either supportive therapy (emotional and educational support) or quality-of-life therapy (a cognitive-behavioral intervention that provided specific intervention strategies to boost happiness and satisfaction in life domains that compromise overall quality of life). Caregivers did not participate directly in the interventions. Setting and Participants--Participants were 28 caregivers from a large lung transplant center in the southeastern United States. Main Outcome Measures--Quality of life (Quality of Life Inventory), mood disturbance (Profile of Mood States-Short Form), and social intimacy (Miller Social Intimacy Scale). Results and Conclusions--Caregivers reported higher quality of life and lower mood disturbance scores, and comparable social intimacy scores relative to the patients for whom they were caring. Caregivers whose patients received quality-of-life therapy reported vicarious gains in quality of life, mood disturbance, and social intimacy, relative to those whose patients received support therapy. Finally, the degree of change in patients' quality of life, mood disturbance, and social intimacy contributed significantly to predicting caregivers' functioning at the 3-month follow-up assessment. These findings suggest that telephone-based quality-of-life therapy has beneficial effects that extend beyond patients to their caregivers. [ABSTRACT FROM AUTHOR]

Study Objectives: The purpose of this study was to determine the impact of a pretransplantation determination of body mass index (BMI) on survival after lung transplantation.Design and Patients: Univariate and multivariate survival analyses of a single institution database consisting of 85 patients who had undergone lung transplantations between March 1994 and October 1998.Setting: University of Florida Health Science Center.Results: Kaplan-Meier survival curves showed that patients who were obese (ie, BMI, > or = 30) at a pretransplantation assessment had a marked decrease in posttransplantation survival time (log rank, p < 0.05; Wilcoxon, p < 0.05). The final Cox regression model revealed that the most powerful predictors of mortality after lung transplantation were higher pretransplantation BMI and the development of obliterative bronchiolitis.Conclusions: Our results suggest that the posttransplantation risk for mortality is possibly three times greater for obese patients than for nonobese patients. Additional study is needed to identify the mechanisms for such higher risk in obese patients. Our data also suggest that transplantation centers should not routinely reject underweight patients (ie, BMI, < 18.5) or overweight patients (ie, BMI, 25 to 29.9) for lung transplantation listing solely on the basis of weight, as their outcomes may not be significantly different than patients with normal BMIs. [ABSTRACT FROM AUTHOR]

Statement of Problem: Data on polymer materials, particularly polyetheretherketone (PEEK) used in restorative dentistry, are scarce, as is knowledge concerning the clinical efficacy of PEEK restorations produced through additive manufacturing when compared with existing indirect materials and techniques., Purpose: The purpose of this randomized clinical trial was to evaluate the clinical performance of additively manufactured and milled PEEK inlays compared with composite resin inlays according to modified United State Public Health Service (USPHS) criteria over a 1-year follow- up., Material and Methods: Participants were allocated into 3 distinct categories based on the materials and techniques used: R1 denoting teeth restored with 3 dimensionally (3D) printed PEEK inlays (N=16), R2 representing teeth restored with milled PEEK inlays (N=16), and R3 indicating the comparator group comprising teeth restored with milled composite resin inlays (N=16). After the placement of inlay restorations, evaluations were conducted at 3 time points (T): baseline (T0), 6 months (T1), and 12 months (T2) by using the modified USPHS criteria for assessing anatomic form, color match, marginal discoloration, marginal adaptation, surface texture, secondary caries, retention, and postoperative sensitivity. Ordinal data were analyzed using the Kruskal-Wallis test, followed by the Dunn post hoc test for between group comparisons, as well as the Friedman test, followed by the Nemenyi post hoc test for within group comparisons (α=.05)., Results: Across all parameters and intervals, most of the restorations within each group exhibited an alfa score, with no statistically significant differences noted (P>.05). However, concerning color match, all restorations within the PEEK groups received a bravo score, indicating a statistically significant difference in intergroup comparison between the milled composite resin groups and the PEEK group (P<.001). However, no significant variances were noted in the scores evaluated across different follow-up periods (P>.05)., Conclusions: Subtractive and additive manufacturing techniques, as well as PEEK and composite resin materials together, offer clinically acceptable functioning restorations over 1 year. PEEK material can be used as a suitable alternative to commonly used indirect composite resin intracoronal restorations in posterior areas. Improvements in terms of surface texture and esthetics are required., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Background: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population., Objective: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure., Methods: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h., Results: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%., Conclusion and Relevance: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.

Ambulatory extracorporeal membrane oxygenation (ECMO) has shown promise as a bridge to lung transplantation. The primary goal of ambulatory ECMO is to provide enough gas exchange to allow patients to participate in preoperative physical therapy. Various strategies of ambulatory ECMO are utilized depending upon patients' need. A wide spectrum of ECMO configurations is available to tackle this situation. We discuss those configurations in this article., Competing Interests: Conflict of interestThe authors declare no competing interests., (© Indian Association of Cardiovascular-Thoracic Surgeons 2021.)

There is a controversy about whether endometriosis-associated ovarian cancer (EAOC) might represent a different entity from the corresponding ovarian cancer occurring de novo, in the absence of endometriosis. This study investigated the clinical-pathologic characteristics and outcome of EAOC compared with other ovarian carcinomas that are not associated with endometriosis (non-EAOC) in a large cohort. Seven hundred two patients meeting the inclusion criteria were further subclassified as group I when patients had ovarian carcinoma associated with or arising within endometriosis (EAOC) and group II when patients had non-EAOC. Age, gross features, histologic type, International Federation of Gynecology and Obstetrics stage, and disease-free survival (DFS) were compared between the groups. One hundred sixty-eight (23.9%) patients had EAOC, whereas 534 (76.1%) patients had non-EAOC. EAOCs were mostly endometrioid and clear cell type. Patients with EAOC were younger, present early, and had a lower rate of recurrence when compared with patients with non-EAOC, P<0.001. Patients with EAOC had longer DFS time, 51.9 mo (95% confidence interval, 44.9-58.8) versus 30.5 mo (95% confidence interval, 27.7-33.3) in non-EAOC patients. The 5 yr Kaplan-Meier estimate of DFS rate was 70% in 166 patients of group I and was 39.3% in 532 patients of group II, P<0.001. On multivariate analysis, International Federation of Gynecology and Obstetrics staging, histologic type, and treatment were the only significant factors affecting the hazards of recurrence. Patients with tumors associated with endometriosis are usually, younger, present early, have lower rate of recurrence, longer DFS, and their tumors are of lower grade and are more likely endometrioid or clear cell carcinoma.

Background: Patient outcomes post-lung transplant remain inferior to other types of solid organ transplantation. We investigated whether the presence of potentially pathogenic bacteria (PPB) in donor lung bronchial cultures was associated with adverse outcomes postoperatively., Methods: All patients who underwent lung transplantation between August 2015 and April 2017 at the University of Kentucky Medical Center were retrospectively reviewed. Retransplants, patients with bronchiectasis (including cystic fibrosis), and individuals who received organs from donation after cardiac death (DCD) donors were excluded. The remaining subjects were separated into two groups: individuals whose donor bronchial cultures grew PPB, and those whose cultures either returned negative for PPB or were sterile. 30-day mortality rates as well as the incidence of grade 3 primary graft dysfunction (PGD) and acute kidney injury (AKI) at both 24 and 72 hours post-transplant were calculated. The duration of mechanical ventilation postoperatively was also recorded., Results: Thirty two subjects comprised the study population. 20 patients (63%) had growth of PPB on donor cultures, while 12 (37%) did not. Patients with PPB had a significantly greater number of days on the ventilator postoperatively compared to those with no PPB (mean = 11.3 and median = 5.0 vs mean = 5.8 and median = 3.0, respectively, P = 0.0232). Subsequent regression analysis revealed this association to not be influenced by recipient lung allocation score (LAS), donor age, donor smoking history, recipient mean pulmonary artery pressure (mPAP) value, and/or use of cardiopulmonary bypass at the time of transplantation. Neither 30-day survival nor incidence of Grade 3 PGD and AKI at 24 or 72 hours post-transplant differed between the two groups (P > 0.05)., Conclusion: The recovery of PPB in donor lung cultures was associated with a longer duration of mechanical ventilation postoperatively in lung transplant recipients., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Lung retransplantation (ReTx) comprises an increasing share of lung transplants and recently has shown improved outcomes. The aim of this study was to identify risk factors affecting overall survival after pulmonary ReTx., Methods: The United Network for Organ Sharing database was used to identify patients undergoing lung transplantation at our institution from 1995 to 2014. Of the total 542 lung transplants performed, 87 (16.1%) were ReTxs. The primary outcome was overall survival. Multivariate Cox regression models were used to assess the effect of recipient and donor characteristics on survival., Results: Of the patients who underwent ReTx, median survival was 2 years. Predictors of worse survival include recipient age between 50 and 60 years (relative risk, 4.3; p = 0.02) or older than 60 years (relative risk, 10.2; p < 0.001), and time to ReTx of less than 2 years (relative risk, 3.8; p = 0.01). ReTx for bronchiolitis obliterans syndrome had longer median survival than for restrictive chronic lung allograft dysfunction (2.7 years vs 0.9 years; p = 0.055). Overall survival of ReTx patients after initiation of the lung allocation score was not significantly different (p = 0.21)., Conclusions: Lung ReTx outcomes are significantly worse than for primary transplantation but may be appropriate in well-selected patients with certain diagnoses. Lung ReTx in patients older than 50 years or within 2 years of primary lung transplantation was associated with decreased survival. Further work is warranted to identify patients who benefit most from ReTx., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Acute cellular rejection (ACR) is a major early complication after lung transplantation (LT) and is a risk factor for chronic rejection. Induction immunosuppression has been used as a strategy to reduce early ACR. Recently, our LT program changed our primary induction protocol from basiliximab with standard maintenance immunosuppression to alemtuzumab induction with reduced dose maintenance immunosuppression. The objective of this study was to compare incidence of ACR after this change in the first 6 months after transplantation., Methods: A retrospective, cohort review of patients 18 years or older, which received their first LT between January 2010 and September 2012., Results: The primary outcome was comparison of average lung biopsy scores at 6 months. Secondary outcomes included development of grade A2 or higher rejection, infectious outcomes, overall graft and patient survival. At 6 months, the average biopsy score was significantly lower in the alemtuzumab group than the basiliximab group (0.12 ± 0.29 vs 0.74 ± 0.67; P < 0.0001) (Table 2). Grade 2 or higher rejection was significantly higher in the basiliximab group (P < 0.0001)., Conclusions: Alemtuzumab provided superior outcomes in regard to average biopsy score and lower incidence of grade 2 or higher rejection at 6 months. There were no differences in infectious complications or overall graft or patient survival between the 2 groups.

Background: Egypt has one of the highest incidences of IUGR. The current study investigates the effect of heavy metals toxicity as risk factors of IUGR and determines the possible role of increased apoptosis in their pathogenesis., Methods: This study was conducted in Assiut, Egypt, included 60 women diagnosed to have IUGR. We measured lead and cadmium levels in blood besides arsenic and cadmium levels in urine. Neonatal scalp hair sample were analyzed for arsenic content. Quantitative determination of human placental Bcl-2 and caspase-3 were performed., Results: There are significantly higher levels of heavy metals and caspase-3 and lower levels of placental Bcl-2 in the IUGR group. The levels of heavy metals were positively correlated with caspase-3 while negatively correlated (except cadmium) with Bcl-2 levels., Conclusions: There is an alarming high level of heavy metals toxicity in Egypt that was positively correlated to IUGR. Increased placental apoptosis may be one of the possible mechanisms behind the effect., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Long-term outcomes after lung transplantation are limited due to chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS) is the most common form of obstructive CLAD and its definition derives from spirometric measurements. Given the importance of this diagnosis, both the accuracy and reliability of the definition of CLAD are crucial in understanding the pathophysiology of this disease to develop therapeutic options and influence outcome after lung transplantation., Methods: A web-based survey was designed and distributed to members of the Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) to better understand the accuracy and reliability of pulmonary function criteria in diagnosing BOS. Spirometric data from five patient scenarios that were discordant among reviewers regarding BOS determination from the Assessment of Immunosuppressive Regimen in Suppressing Acute and Chronic Rejection (AIRSAC) trial were randomly selected and summarized in this survey. Survey questions included the respondent's general understanding of the BOS definition, the determination of BOS, and difficulties with the current BOS definition., Results: Eighty-seven respondents from the Pulmonary Council of the ISHLT responded to this survey. There was an overall 70% interobserver agreement regarding the presence or absence of BOS. Among those who agreed upon the presence of BOS, there was a 41% interobserver agreement regarding its time of onset. Despite this variability, the majority of respondents were not only familiar and agreed with the BOS criteria, they also felt confident in applying these criteria., Conclusions: Our survey identified potential limitations with the current criteria for diagnosing BOS. With recognition of the various CLAD phenotypes, further refinements of these diagnostic criteria will allow for an improved ability to identify and characterize patients who develop or are at risk for BOS, prognosticate outcomes, and, most importantly, marshal in future strategies directed at treating and preventing chronic lung dysfunction after lung transplantation., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Unlabelled: We studied the level of lipid peroxide, nitric oxide (NO), trace elements (TEs), and microparticles (MPs) in Gaucher disease (GD) before and after 1 year of enzyme replacement therapy (ERT). A total of 15 children with GD and 15 healthy controls were enrolled in this study. Serum level of lipid peroxide, NO, and TEs was determined. The MPs were detected by flow cytometry. The level of lipid peroxide was significantly higher in the patients than in the controls even after ERT. Although NO level was normalized in the patients after ERT, zinc and copper were still lower in the patients after ERT. The percentages of various MPs were significantly higher in the patients than in the controls both before and after ERT. There were positive correlations between chitotriosidase and both lipid peroxide and total MPs., Conclusion: The GD is associated with alteration in oxidant and antioxidant status and high level of circulating MPs., (© The Author(s) 2013.)

Background: Cytomegalovirus (CMV) is the most common opportunistic infection in lung transplantation. A recent multicenter, randomized trial (the AIRSAC study) comparing sirolimus to azathioprine in lung transplant recipients showed a decreased incidence of CMV events in the sirolimus cohort. To better characterize this relationship of decreased incidence of CMV events with sirolimus, we examined known risk factors and characteristics of CMV events from the AIRSAC database., Methods: The AIRSAC database included 181 lung transplant patients from 8 U.S.-based lung transplant centers that were randomized to sirolimus or azathioprine at 3 months post-transplantation. CMV incidence, prophylaxis, diagnosis and treatment data were all prospectively collected. Prophylaxis and treatment of CMV were at the discretion of each institution., Results: The overall incidence of any CMV event was decreased in the sirolimus arm when compared with the azathioprine arm at 1 year after lung transplantation (relative risk [RR] = 0.67, confidence interval [CI] 0.55 to 0.82, p < 0.01). This decreased incidence of CMV events with sirolimus remained significant after adjusting for confounding factors of CMV serostatus and CMV prophylaxis., Conclusions: These data support results from other solid-organ transplantation studies and suggest further investigation of this agent in the treatment of lung transplant recipients at high risk for CMV events., (Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Acute rejection remains a major source of morbidity after lung transplantation. Given the importance of this diagnosis, an international grading system was developed to standardize the diagnosis of acute lung-allograft rejection. The reliability of this grading system has not been adequately assessed by previous studies., Methods: We examined the level of agreement in grading transbronchial biopsy specimens obtained from a large multicenter study (AIRSAC [Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen vs Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation] trial). Biopsy specimens were initially graded for acute rejection and lymphocytic bronchiolitis by the site pathologist and subsequently graded by a central pathologist. Reliability of interobserver grading was evaluated using Cohen κ coefficients., Results: A total of 481 transbronchial biopsy specimens were graded by both the site and central pathologists. The overall concordance rates were 74% and 89% for grade A and grade B biopsy specimens, respectively. When samples from biopsies performed at different time points after transplantation were assessed, there was a higher level of agreement early (≤ 6 weeks) after transplant compared with later time points for acute rejection. However, there was still only moderate agreement for both grade A (κ score 0.479; 95% CI, 0.29-0.67) and grade B (κ score 0.465; 95% CI, 0.08-0.85) rejection., Conclusions: These results expand upon previous reports of interobserver variability in grading transbronchial biopsy specimens after lung transplantation. Given the variability in grading these specimens, we advocate further education of the histopathologic findings in lung transplant biopsy specimens, as well as revisiting the current criteria for grading transbronchial biopsy specimens to improve concordance among lung transplant pathologists., Trial Registry: ClinicalTrials.gov; No. NCT00321906; URL: www.clinicaltrials.gov.

Introduction: The aim of this report is to study the graft and patient survival in a large cohort of recipients with an analysis of factors that may affect the final outcomes., Methods: Between March 1976 and March 2008, 1967 consecutive live-donor renal transplants were carried out. Various variables that may have an impact on patients and/or graft survival were studied in two steps. Initially, a univariate analysis was carried out. Thereafter, significant variables were embedded in a stepwise regression analysis., Results: The overall graft survival was 86.7% and 65.5%, at 5 and 10 years, respectively. The projected half-life for grafts was 17.5 years and for patients was 22 years. Five factors had an independent negative impact on graft survival: donor's age, genetic considerations, the type of primary immunosuppression, number of acute rejection episodes, and total steroid dose during the first 3 months after transplantation., Conclusions: Despite refinements in tissue matching techniques and improvements in immunosuppression protocols, an important proportion of grafts is still lost following living donor kidney transplantation, presumably due to chronic allograft nephropathy.

Idiopathic pulmonary fibrosis (IPF) is characterised by myofibroblast proliferation leading to architectural destruction. Neither the origin nor the continued proliferation of myofibroblasts is well understood. Explanted human IPF lungs were stained by immunohistochemistry for calretinin, a marker of pleural mesothelial cells (PMCs). Chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) lungs acted as controls. The number of PMCs per 100 nucleated cells and per photomicrograph was estimated along with the Ashcroft score of fibrosis. Mouse PMCs expressing green fluorescent protein (GFP) or labelled with nanoparticles were injected into the pleural space of mice given intranasal transforming growth factor (TGF)-β1. Mouse lungs were lavaged and examined for the presence of GFP, smooth muscle α-actin (α-SMA) and calretinin. Calretinin-positive PMCs were found throughout IPF lungs, but not in COPD or CF lungs. The number of PMCs correlated with the Ashcroft score. In mice, nanoparticle-laden PMCs were recoverable by bronchoalveolar lavage, depending on the TGF-β1 dose. Fluorescent staining showed α-SMA expression in GFP-expressing PMCs, with co-localisation of GFP and α-SMA. PMCs can traffic through the lung and show myofibroblast phenotypic markers. PMCs are present in IPF lungs, and their number correlates with IPF severity. Since IPF presumably begins subpleurally, PMCs could play a pathogenetic role via mesothelial-mesenchymal transition.

Background: Since the advent of ex vivo lung perfusion (EVLP), there has been increased focus on swine models of lung transplantation; however, the anatomic differences between human and swine lungs and the technical challenges in performing porcine lung transplantation are not well described in the surgical literature., Methods: Surgically important anatomic variations are described, and the technical measures taken to address them during harvest and transplantation are introduced., Results: There are three surgically important anatomic variations in pigs. First, the right cranial lobe bronchus arises directly from the trachea, which makes right lung transplantation technically challenging if not prohibitive. Second, the left hemi-azygos vein is fully developed and courses upward through the posterior mediastinum, where it crosses the left pulmonary hilum and drains directly into the coronary sinus. During transplantation, this vein is ligated and dissected away to expose the underlying left pulmonary hilar structures. Third, the right inferior pulmonary vein crosses the midline to drain into the left atrium immediately adjacent to the left inferior pulmonary vein. During donor lung preparation, the right inferior pulmonary vein is ligated distally from the left atrium, which leaves an adequate atrial cuff around the left sided pulmonary veins for later anastomosis., Conclusion: Experimental porcine lung transplantation is technically demanding. We have found recognition of the above described anatomical differences and technical nuances facilitate transplantation and provide reproducible results., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Study Aims: Non-invasive predictors of medium/large oesophageal varices (LOVs) could reduce the number of screening endoscopies. As portal hypertension is a consequence of liver fibrosis, serum fibrosis markers were evaluated together with other variables as possible non-invasive predictors of medium OV/LOV., Patients and Methods: A total of 154 cirrhotic patients with splenomegaly and 30 healthy control subjects were recruited in a prospective study in two gastroenterology centres in Upper Egypt. Clinical parameters assessed included Child-Pugh class, liver size and ascites. Laboratory parameters included complete blood count, liver function tests, and aspartate aminotransferase (AST)/platelet ratio. Transforming growth factor-β(1) (TGF-β(1)), alpha(2) macroglobulin (A(2)M) and hyaluronic acid (HA) were assayed. Ultrasonographic examination was done for assessment of liver span, portal vein diameter and detection of minimal ascites. Oesophageal varices were diagnosed and graded by oesophagogastroduodenoscopy., Results: Fifty-four patients (35%) had no or small varices and 100 (65%) patients had medium OV/LOV by endoscopy. On multivariate analysis, the independent predictors of medium OV/LOV were the presence of ascites (β=0.258, p=0.047) and serum HA (β=0.449, p=0.009). The receiver operating characteristic curve for HA showed the area under the curve to be 0.916. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of HA at a cut-off value of 207μgl(-1) were 94%, 77.8%, 88.7%, 87.5% and 88.3%, respectively., Conclusions: The presence of ascites and serum HA level higher than 207μgl(-1) can predict the presence of medium OV/LOV in cirrhotic patients. This would help physicians to identify patients who would most likely benefit from screening endoscopy and thus, reduce costs and discomfort from unnecessary endoscopic procedures., (Copyright © 2011 Arab Journal of Gastroenterology. Published by Elsevier Ltd. All rights reserved.)

Background: Sirolimus (rapamycin) is a potent anti-proliferative agent with immunosuppressive properties that is increasingly being used in solid-organ and hematopoietic stem cell transplantation. In addition, this drug is being investigated for treatment of a broad range of disorders, including cardiovascular disease, malignancies, tuberous sclerosis, and lymphangeioleiomyomatosis. In this study, we found an increased risk of venous thromboembolism (VTE) in lung transplant recipients treated with a sirolimus (SIR)-based immunosuppressive regimen., Methods: One hundred eighty-one lung transplant recipients were enrolled in a prospective, multicenter, randomized, open-label trial comparing a tacrolimus (TAC)/SIR/prednisone immunosuppression regimen with a TAC/azathioprine (AZA)/prednisone immunosuppressive regimen. The differences in rates of VTE were examined., Results: There was a significantly higher occurrence of VTE in the SIR cohort [15 of 87 (17.2%)] compared with the AZA cohort [3 of 94 (3.2%)] (stratified log-rank statistic = 7.44, p < 0.01). When adjusted for pre-transplant diagnosis and stratified by transplant center, this difference remained essentially unchanged (hazard ratio for SIR vs AZA = 5.2, 95% confidence interval 1.4 to 19.5, p = 0.01)., Conclusion: Clinicians prescribing SIR should maintain a high level of vigilance for VTE, particularly among patients with other risk factors for this complication., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Rationale: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation., Objectives: To determine the potential benefit versus risk of sirolimus in lung transplantation., Methods: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups., Measurements and Main Results: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infection was decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P < 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study., Conclusions: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).

We sought to investigate the role of autopsy diagnoses in lung transplantation by comparing the clinically derived cause of death with autopsy deduced cause of death in a cohort of lung transplant recipients. We retrospectively reviewed all consecutive autopsy findings on lung transplant recipients transplanted between March 1994 and March 2007. We reviewed medical records and our lung transplant database to determine the clinical diagnosis of cause of death based on the clinical assessment and discharge summary at the time of death. Our study showed that 21% of the autopsies performed on lung transplant recipients at our institution revealed findings unsuspected at the time of death. Myocardial infarction, pulmonary embolism, high grade acute cellular rejection and infections were the most frequently missed diagnoses. The autopsy remains a useful tool in confirming diagnostic accuracy in lung transplant recipients., (© 2009 John Wiley & Sons A/S.)

Background: Limited information is available about the prevalence of pulmonary hypertension diagnosed by right heart catheterization (RHC) in patients with cystic fibrosis being evaluated for lung transplantation. It is unclear whether there are factors that can predict the presence of pulmonary hypertension and whether the presence of pulmonary hypertension influences patient outcomes., Methods: The study included 57 unique and consecutive adult patients (33 women) with cystic fibrosis who underwent lung transplant evaluation at the University of Florida., Results: The average age at evaluation was 31.8 +/- 10 years. All patients were in New York Heart Association class III. The median (interquartile range) of mean pulmonary artery pressure (PAP) was 26 (24-30) mm Hg. Thirty-six patients (63.2%) had pulmonary hypertension (mean PAP >or= 25 mm Hg) and had a significantly higher degree of hypoxemia and oxygen requirements. Echocardiography evidenced limitations for the diagnosis of pulmonary hypertension. The 5-year mortality rate was similar in patients with or without pulmonary hypertension; however, it was higher in 7 patients identified by cluster analysis and in patients with a left ventricular ejection fraction < 55%., Conclusions: More than half of our patients with cystic fibrosis and advanced lung disease have elevation of PAP, usually of mild degree. A lower left ventricular ejection fraction, but not the presence of pulmonary hypertension, was associated with worse outcomes., (Copyright (c) 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate the relationship between vascular endothelial growth factor (VEGF), p53, and the H-ras oncogene and different clinicopathological parameters in Egyptian patients with Schistosoma-associated transitional cell carcinoma of the bladder., Methods: The study included 50 patients with transitional cell carcinoma for whom radical cystectomy and urinary diversions were carried out. VEGF and p53 protein expressions were evaluated with an immunohistochemical staining method, and H-ras oncogene mutations were analyzed with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique., Results: High grade tumors revealed higher p53 immunostaining than low grade tumors (P = 0.016). p53 and VEGF protein expressions, as well as H-ras oncogene mutations, had an insignificant impact on patient outcomes (P = 0.962, P = 0.791, and P = 967, respectively). Cancer extension to regional lymph nodes was associated with poor outcomes (P = 0.008)., Conclusion: VEGF, p53 and the H-ras oncogene have no relation to patient survival and outcome in Schistosoma-associated transitional cell carcinoma.

Objective: To observe the effect of naloxone on the lung function of potential lung transplant donors with neurogenic pulmonary edema., Design and Interventions: Donors aged 16 to 55 years without any factors to contraindicate lung donation (pneumonia, pulmonary contusion, etc) were included. Ventilator settings were standardized to a tidal volume of 10 to 12 mL/kg, an FIO2 of 0.40, and a respiratory rate that kept PCO2 between 35 and 45 mm Hg. Chest physiotherapy, nebulizer treatments, and frequent suctioning were undertaken. Baseline arterial blood gas analysis and an oxygen challenge were performed. The patients were then given 8 to 10 mg of naloxone. Oxygen challenges and arterial blood gas analyses were repeated every 4 to 6 hours. The data were analyzed by using a paired t test, and each patient served as his or her own control., Setting: These interventions were performed on the 19 LifeQuest donors who met the set criteria from July 2002 to July 2004., Results: The PaO2 on the oxygen challenge immediately after administration of naloxone increased from 329 (SD 177) to 363 (SD 191) mm Hg, although the increase from baseline was not significant. The PaO2 from the second oxygen challenge (median time, 7 hours after administration of naloxone) increased to 413 (SD 177) mm Hg (P<.01).

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis noted in the pulmonary parenchyma. Pleural mesothelial cells (PMC) are metabolically dynamic cells that cover the lung and chest wall as a monolayer and are in intimate proximity to the underlying lung parenchyma. The precise role of PMC in the pathogenesis of pulmonary parenchymal fibrosis remains to be identified. Transforming growth factor (TGF)-beta1, a cytokine known for its capacity to induce proliferative and transformative changes in lung cells, is found in significantly higher quantities in the lungs of patients with IPF. High levels of TGF-beta1 in the subpleural milieu may play a key role in the transition of normal PMC to myofibroblasts. Here we demonstrate that PMC activated by TGF-beta1 undergo epithelial-mesenchymal transition (EMT) and respond with haptotactic migration to a gradient of TGF-beta1 and that the transition of PMC to myofibroblasts is dependent on smad-2 signaling. The EMT of PMC was marked by upregulation of alpha-smooth muscle actin (alpha-SMA), fibroblast specific protein-1 (FSP-1), and collagen type I expression. Cytokeratin-8 and E-cadherin expression decreased whereas vimentin remained unchanged over time in transforming PMC. Knockdown of smad-2 gene by silencing small interfering RNA significantly suppressed the transition of PMC to myofibroblasts and significantly inhibited the PMC haptotaxis. We conclude that PMC undergo EMT when exposed to TGF-beta1, involving smad-2 signaling, and PMC may be a possible source of myofibroblasts in IPF.

Primary graft dysfunction and rejection are common complications in lung transplant recipients. Increased expression of thioredoxin-1 (Trx), a 12-kDa redox-regulatory protein, has been reported in multiple lung pathophysiological conditions involving oxidative and inflammatory mediated injury including graft rejection in canine and rat models of lung transplantation. Our objective was to determine whether increased Trx expression is associated with progression of rejection pathophysiology in human lung transplant recipients. Bronchoalveolar lavage (BAL) fluid and transbronchial biopsy samples were collected as a routine part of post-transplant clinical care from 18 lung transplant patients from our adult lung transplant programme. Lung transplant recipient profile included age/sex, ethnic background, days on ventilator, total ischaemic time, and cytomegalovirus (CMV) status. Based on histopathological grading criteria, patients were divided into two groups, rejecting (A1/A2 or B1) and non-rejecting (A0/B0). Rejecting and non-rejecting group total BAL cell counts and differential cell counts for neutrophils, macrophages, lymphocytes and eosinophils as well as total BAL cell Trx levels were analysed. Total BAL cell counts were significantly (p <0.05) elevated in graft rejecting versus non-rejecting patients. Differential BAL macrophage counts were comparable in rejection and non-rejection groups, whereas there were significant increases in neutrophils and lymphocytes but not eosinophils in patients with rejection versus non-rejection pathology (p <0.05). Total ischaemic time and days on ventilator in rejection and non-rejection groups were comparable. However, Trx levels were significantly elevated in BAL cells from graft-rejecting patients compared with non-rejecting patients (p <0.05). These data suggest that surveillance monitoring of BAL Trx levels after lung transplantation can serve as a biomarker to assess severity of graft rejection.

Purpose: We performed a critical analysis of the results of radical cystectomy for invasive bladder carcinoma treated at 1 center., Materials and Methods: Between 1970 and 2000, 2,090 men and 630 women with invasive bladder cancer were treated with 1-stage radical cystectomy and urinary diversion. Followup ranged from 0 to 34.2 years with a mean of 5.5 +/- 5.7. Survival data were correlated to patient and tumor characteristics using univariate and multivariate analysis., Results: Postoperative mortality was 2.6%. Squamous tumors accounted for 49.4% of cases, transitional cell carcinoma for 36.4% and adenocarcinoma for 9.6%. Regional lymph nodes were involved in 20.4% of cases. The 5 and 10-year disease-free survival rates were 55.5% and 50.03%, respectively. Evidence was provided that tumor stage, histological grade and lymph node status are the only independent variables which affect survival probability., Conclusions: Contemporary cystectomy can be performed with minimal mortality. Radical cystectomy for organ confined disease is followed by good therapeutic results and enhances the possibilities for functional restoration. With stage progression there is a stepwise reduction in survival probability. The radical operation can provide disease-free survival for an important subgroup of node positive cases (27.3%). Additional therapy is needed to improve the oncological outcome for advanced locoregional disease.

Background: Gastroparesis following lung transplantation can complicate medical management leading to malnutrition, weight loss, and erratic absorption of immunosuppressive medications, which are all important factors in the success of grafts. Gastric electrical stimulation has been shown to reduce the frequency of nausea and vomiting and lead to weight gain in patients with gastroparesis refractory to standard medical treatment; however, it has not yet been reported as being used for the treatment of gastroparesis in lung transplant recipients., Methods: We report the case of a female bilateral lung transplant recipient suffering from severe gastric reflux and severe gastroparesis, who was successfully treated with simultaneous creation of a laparoscopic Nissen fundoplication and placement of a gastric stimulator., Results: The patient noted an immediate and sustained decrease in her symptoms of nausea and vomiting, and an increased appetite, and less variability in the serum levels of her immunosuppressive medication., Conclusion: Lung transplant recipients with severe gastroparesis and reflux may benefit from Nissen fundoplication and gastric electrical stimulation.

Background: The emotional and physical well-being of lung transplant patients is enhanced by the availability and stability of a primary caregiver., Methods: We describe the quality of life (QOL), mood, caregiving strain and benefits, and social intimacy of 73 lung transplant caregivers who completed the QOL Inventory, SF-36 Health Survey, Profile of Mood States, Caregiver Strain Index, Caregiver Benefit Index, and Miller Social Intimacy Scale., Results: Clinically low QOL was reported by 17.8-35.6% of spouses. Relative to a normative sample, spouses reported significantly lower physical (z = 4.01, p < 0.001) and emotional (z = 7.01, p < 0.001) QOL. Over half (56.2%) had clinically elevated caregiving strain. Heightened physical strain (80.8%), inconvenience (79.5%), feeling confined (72.6%), feeling upset that patient has changed so much (69.9%) contributed most to caregiver strain, while discovering inner strength (60.3%), support from others (53.4%), and realizing what is important in life (42.5%) were noted caregiving benefits. Higher caregiving strain was associated with more mood disturbance (r = 0.42, p < 0.001), lower emotional QOL (r = -0.39, p < 0.002), lower social intimacy (r = -0.37, p < 0.002), and longer disease duration (r = 0.55, p < 0.001)., Conclusion: Spouses of patients awaiting lung transplantation may experience QOL deficits and high caregiver strain. Interventions to improve QOL and reduce caregiver strain are needed.

We describe a young man with cystic fibrosis who underwent bilateral sequential lung transplantation (BSLT) and a subsequent right single-lung re-transplant for bronchiolitis obliterans syndrome (BOS). Destruction of the retained left lung with recurrent pneumonia, worsening bronchiectasis and abscess formation was treated with a left lower lobectomy and a subsequent complete pneumonectomy. The patient tolerated the procedures and is alive and well 18 months after left pneumonectomy. In the setting of BOS, allograft pneumonectomy can be performed safely to remove non-functioning infected tissue.

Background: Osteoporosis is known to complicate outcomes after lung transplantation (Tx)., Methods: To determine the efficacy of bisphosphonate therapy combined with the osteogenic stimulus of mechanical loading, 30 lung transplant recipients (LTRs) were randomly assigned either to alendronate (10 mg/day; n = 10), alendronate (10 mg/day) + resistance exercise (n = 10) or to a control group (n = 10). Alendronate was initiated at 7 days after Tx. Bone mineral density (BMD) of the lumbar spine was measured by dual-energy X-ray absorptiometry before and 2 and 8 months after Tx. Resistance training was initiated at 2 months after Tx and consisted of lumbar extension exercise performed 1 day/week for 6 months., Results: Lumbar BMD decreased significantly to below pre-transplant baseline at 2 months after Tx in controls (-12.5 +/- 2.1%), but not in the alendronate (1.5 +/- 1.2%) or alendronate + training (1.5 +/- 0.9%) groups. At 8 months after Tx, lumbar BMD in controls was 14.1 +/- 3.9% below baseline (p < or = 0.05), but was 1.4 +/- 1.1% above baseline in alendronate recipients (p > or = 0.05). The alendronate + training group showed a significantly increased lumbar BMD with values 10.8 +/- 2.3% greater than before Tx., Conclusions: These results suggest that resistance exercise plus alendronate is more effective than alendronate alone in restoring BMD. Anti-osteoporosis therapy in LTRs should include both an anti-resorptive agent and an osteogenic stimulus, such as mechanical loading.

Background/aims: Protocol biopsy is an important strategy which assesses the histological changes that can occur in the renal allograft and adversely affect its outcome. We aimed to evaluate histological changes in long-term living donor transplants., Methods: Elective biopsies were done for 120 live donor renal transplant recipients with well-functioning grafts and no rejection history at least 1 year or more after transplant. All patients had serum creatinine levels <2 mg/dl. The histopathological findings using the chronic allograft damage index score were correlated with different clinical and immunological parameters., Results: Chronic tubulointerstitial fibrosis was the most prevalent finding (85% of cases), mostly of mild degree. Normal biopsies were reported in only 7.5% of cases, whereas chronic cyclosporine nephrotoxicity was detected in 5.8% of biopsies. Posttransplant hypertension was significantly correlated with glomerulosclerosis, and posttransplant diabetes with glomerulosclerosis, mesangial matrix increase, tubular atrophy and interstitial fibrosis. The main risk factors associated with a high chronic allograft damage index score were DR mismatching, posttransplant diabetes and time of biopsy. All histopathological changes increased with advancing donor age and declining graft function., Conclusion: Elective biopsies showed that histopathological findings do exist even with stable renal function that may pave the way for predicting long-term graft outcome., (Copyright (c) 2006 S. Karger AG, Basel.)

Objective: To study proliferating cell nuclear antigen (PCNA) over expression and angiogenesis with their relationship to tumor parameters in squamous cell carcinoma of the urinary bladder in patients who underwent radical cystectomy., Patients and Methods: The mean age of the patients was 53.53 years (range; 29-70 years) and the males were 98 of 154. Sections from paraffin embedded tissues were retrieved and stained with antibodies against PCNA for proliferation and CD34 for angiogenesis using immunohistochemical technique. Fisher's exact test was used to evaluate the relationship between categorical variables and the Kaplan-Meier procedure was used to assess survival outcomes. The Cox regression model was used for multivariate analysis., Results: The median follow up period was 65 months. microvessel density (MVD), PCNA, tumor grade, P-stage, DNA ploidy, lymph node status had a significant impact on the 5-year survival of patients in univariate analysis. In Cox proportional hazard model, MVD, PCNA, DNA ploidy and stage sustained their significant impact on survival of the patients., Conclusions: MVD, PCNA, DNA ploidy and stage are independent prognostic factors in patients with squamous cell carcinoma of the urinary bladder.

The primary study aim was to examine sex differences in health-related quality of life (HRQoL) in a sample of 37 patients (20 men, 17 women) with chronic obstructive pulmonary disease (COPD) who were evaluated both before and after lung transplantation. Main outcome measures were change in HRQoL from pre- to post-transplantation assessment as measured by the Short Form-36 Health Survey, Transplant Symptom Frequency Questionnaire, forced expiratory volume in 1 second percent predicted, and 6-minute walk test. Study findings showed (1) substantial gains in HRQoL, lung function, and physical endurance for most patients, (2) significant sex differences, with women reporting more frequent and problematic symptoms and a lower percentage gain in HRQoL than men, and (3) a higher percentage gain on spirometry findings after transplantation for women than for men. We conclude that there may be a need to examine the post-transplantation symptom profile of women and men separately.