Sirolimus-induced pneumonitis after renal transplantation: a single-center experience

Purpose

Sirolimus is a potent immunosuppressive agent used with increasing frequency in kidney transplantation. However, sirolimus can increase the rate of unexplained interstitial pneumonitis. The aim of this study was to evaluate the clinical characteristics of sirolimus-induced pneumonitis and the therapeutic results in renal transplant recipients.

Patients and methods

Seventy-two patients received sirolimus, conversion or de novo regimen, at our center between January 2007 and April 2011. Twelve of the 72 patients (16.7%) developed interstitial pneumonitis. The patients were divided into three groups according to the following indications of sirolimus use: de novo, early conversion, and late conversion groups.

Results

The mean duration of follow-up was 11.0 ± 11.5 months. The mean blood level of sirolimus measured by microparticulate enzyme immunoassay was 16.5 ± 7.4 ng/mL at the time of diagnosis. The mean time from the start of sirolimus to pneumonitis onset was 14.7 ± 8.0 months. The clinical presentation included fever, cough, dyspnea, general weakness, and periorbital edema. In most cases, radiological imaging tests revealed bilateral lower-lobe involvement. Bronchoalveolar lavage was performed in three patients and two patients showed lymphocytic alveolitis. Sirolimus was discontinued or reduced for the treatment of pneumonitis. All cases of pneumonitis were resolved within 2 to 4 weeks.

Conclusion

Sirolimus blood level should be monitored tightly and early intervention is important when sirolimus-induced pneumonitis is suspected.     

Epidemiology of pneumonia in kidney transplantation

Background

Pneumonia remains an important cause of morbidity among solid organ transplant recipients.

Methods

We prospectively evaluated all renal transplant patients at our center from July 2003 to December 2008 who had pneumonia that required hospitalization. We gathered data regarding underlying diseases as well as pretransplant, transplant, and posttransplant characteristics. Pneumonia defined according to the Centers for Disease Control and Prevention criteria was classified depending on its origin as community acquired or nosocomial. In all patients, microbiologic samples of respiratory secretions and blood were collected at the physician's discretion. The indication to perform a fiberoptic bronchoscopy was the presence of multiple, bilateral, or diffuse pulmonary infiltrates or the absence of a clinical or radiologic response after 3 days of antimicrobial therapy.

Results

Among 610 kidney transplant recipients, we diagnosed 60 episodes of pneumonia in 54 patients (8.8%), of which 23 had a nosocomial origin (38%) and 37 community acquired (62%). Bacterial infection was the most frequent etiology (44%), followed by fungal in 4 (7%) and viral in 2 (3.5%). The most commonly isolated microorganism in nosocomial pneumonia was Pseudomonas aeruginosa (26%, among which 50% was multidrug resistant). In 34% there was no microbiologic isolation. The most common pathogen among community-acquired pneumonias was Strepococcus pneumoniae (11%). In 54% of cases there was no microbiologic confirmation of disease. The overall accuracy of bronchoalveolar lavage was 72%. A total of 21 patients with pneumonia (35%) were admitted to the intensive care unit; of these, 14 had a nosocomial origin (60%) and 9 (15%) died due to the infection (8 [88%] of whom had nosocomial pneumonia; P = .001).

Conclusions

Our data confirmed that nosocomial pulmonary infections are associated with considerable morbidity and mortality in renal transplant recipients. The performance of invasive procedures is useful for the diagnosis of pneumonia.     

The ratio between metastatic and examined lymph nodes is an independent prognostic factor for patients with resectable middle and distal bile duct carcinoma

Background

The lymph node ratio, defined as the ratio between the number of lymph node metastasis and the total number of lymph nodes examined, has been reported to be an important prognostic factor in other gastrointestinal carcinomas except middle and distal bile duct carcinomas.

Methods

Between 1991 and 2004, 62 consecutive patients who underwent surgery for middle and distal bile duct carcinoma were retrospectively analyzed concerning prognostic factors.

Results

The median number of lymph nodes examined was 12 (range 5 to 38). The overall 5-year survival rates of patients with lymph node ratio of 0, lymph node ratio of 0 to .2, and lymph node ratio >.2 were 62%, 41%, and 0%, respectively. A multivariate analysis revealed that a lymph node ratio >.2 and perineural invasion were independent predictive factors for survival.

Conclusions

Lymph node ratio >.2 is an important factor to predict survival after resected middle and distal bile duct carcinoma.     

Metabolic syndrome and cardiovascular disease in kidney transplantation

Introduction

Metabolic syndrome (MS) is an important cardiovascular risk factor. The aim of this study was to evaluate the incidence of MS in an Italian kidney transplant recipient population and its relationship to the incidence of major adverse cardiovascular events (MACE) after renal transplantation.

Methods

The prevalence of MS was evaluated according to the National Cholesterol Education Program Adult Treatment Panel III criteria among adult recipients who underwent a renal transplant between January 1997 and December 2007. In this period, we prospectively recorded the incidence of MACE to be related to the presence of MS.

Results

We included 425 kidney transplant recipients in the study including 62% males and an overall median age 46 years (interquartile range = 36-54). The prevalence of MS was 41.2% at 6 months after transplantation and 46.6% at 5 years. During the follow-up (median = 5.1 years), 32 patients (7.5%) experienced at least one MACE. The detection of MS at 6 months after transplantation was significantly associated with an increased risk of MACE occurrence (MS IRR = 2.2 P = .05).

Conclusions

Our findings indicated that MS was largely present in the transplant population confirming that as in the general population, it was a significant risk factor for the occurrence of severe cardiovascular disease. Early identification and treatment of patients with MS may improve long-term patient survival.     

Medical students' knowledge about organ transplantation: a South African perspective

Background

Educating physicians about transplantation during undergraduate training can improve organ procurement rates. The aim of this study was to evaluate and analyze the knowledge of medical students regarding transplantation.

Methods

A previously validated self-administered anonymous questionnaire was distributed to all medical students.

Results

Of the 346 participants, 217 (63%) were preclinical students. Their mean age was 21 years (range, 18-33) and 62% were women. Twenty-nine (8%) students were registered as organ donors. One third of all study participants received formal transplantation teaching; a greater proportion of clinical students received teaching compared with the preclinical group (52% vs 22%, P < .05). Knowledge was frequently reported for kidney (88%), liver (81%), bone marrow (78%), and heart (76%) transplantation. Small Intestine (13%), pancreas (9%), and pancreatic islets (4%) were the least recognized organs/tissues. Ninety-six percent and 62% of respondents were aware of kidney and liver living-donor transplants, respectively; the 27% of students with an interest in a surgical career had better knowledge of living-donor transplantation (P < .05). Only 22 (6%) students knew which solid organ transplants were performed in South Africa.

Conclusion

Medical students have limited knowledge about organ transplantation; there is a need for educational intervention early in the medical curriculum.     

Clinical Variables Associated With the Presence of Inflammatory Infiltrates in Patients With Dilated Cardiomyopathy Undergoing Heart Transplantation

Introduction

Idiopathic dilated cardiomyopathy (DCM) is, together with ischemic heart disease, the major cause of end-stage heart failure leading to heart transplantation. However, an unknown percentage of patients with this diagnosis has inflammatory foci found in the histopathological study of the explanted heart. This fact suggests an undetected process of acute myocarditis as the cause of cardiac dysfunction.

Objective

The objective of this study was to identify clinical and echocardiographic variables related to the presence of myocardial infiltrates, as a potential guide to determine which patients should undergo endomyocardial biopsy in DCM.

Materials and Methods

We retrospectively analyzed 161 patients who underwent heart transplantation with a diagnosis of DCM between 1987 and 2007. The presence of inflammatory infiltrates was considered significant when the histopathological study of tissue blocks from the left ventricle showed 1 or more foci per cm² of perivascular or interstitial mononuclear or polymorphonuclear cells, whether or not in the presence of cytolysis.

Results

Seventeen patients (11%) had these inflammatory histological findings; of them, 6 (35%) showed preponderance of eosinophils and 7 (41%) showed areas of cytolysis. The DCM group with inflammatory infiltrates showed significant differences in terms of younger age (45 ± 15 vs 50 ± 11 years; P < .01) and smaller ventricular diameters (P < .05). Male gender was more frequent in this group, and the patients had a poorer clinical status and greater dependence on inotropic drugs.

Conclusions

Inflammatory infiltrates are frequently present in DCM explanted hearts. Although there are no relevant clinical variables to identify subclinical myocarditis, these patients are younger and have smaller ventricular diameters and poorer functional status at the time of transplantation.     

Colecistectomía laparoscópica en pacientes mayores de 80 años

Introduction

The increasing aging of the population also increases the prevalence of symptomatic gallbladder diseases. It is important to analyse their surgical treatment in the elderly.

Methods

All the laparoscopic cholecystectomies performed in our surgery department on patients aged 80 years-old or over from 1992 to 2007 were included in this study.

Results

Laparoscopic cholecystectomy was performed on 133 patients 80 years-old and over, with 63% of them women, and an average age of 83.23 years. Biliary colic (29%) and acute pancreatitis (44%) were the main reasons for surgery. Associated diseases were found in 73% of them. Only 7.5% needed urgent surgery, even although 71% were admitted urgently. There were 13.5% conversions to open surgery, 17% morbidity and 2.3% mortality.

Conclusions

Laparoscopic cholecystectomy can be recommended in symptomatic gallbladder disease in the elderly.     

Sirolimus is Associated With Impaired Hematopoiesis in Heart Transplant Patients? A Retrospective Analysis

Background

Proliferation signal inhibitors may adversely impact bone marrow function. We sought to describe the impact of sirolimus on hemoglobin and erythropoiesis in heart transplant recipients.

Methods

We have conducted a single-center, retrospective analysis of all heart transplant patients treated with sirolimus. We measured serum hemoglobin (Hb) at baseline and at 3 months to determine the prevalence of anemia and change in Hb after sirolimus initiation. We also characterized hematologic profile of patients to gain insights into the effects of sirolimus on erythropoiesis.

Results

There were 84 patients included in the study. The prevalence of anemia increased from 71% to 75% after sirolimus initiation. Anemic patients were more likely to be male (P = .026) and have worse renal function (glomerular filtration rate 49 ± 27 vs 70 ± 42 mL/min; P = .012). A ≥20 g/L drop in Hb was observed in 25% of the overall cohort. Patients investigated for anemia (n = 67) had a low Hb (111 ± 24 g/L), normal mean corpuscular volume (87 ± 47 FL), and low serum iron levels (10 ± 5 μmol/L) and transferrin saturation (0.22 ± 0.12). Serum ferritin was variable (263 ± 370 μg/L). Bone marrow evaluation in 19 patients revealed adequate marrow iron stores in all cases.

Conclusion

Anemia is prevalent in heart transplant patients treated with sirolimus and increases over time. Patients have a characteristic hematologic profile suggestive of anemia of chronic disease and functional iron deficiency.     

Angiogenesis and Ewing sarcoma--relationship to pulmonary metastasis and survival

Background/Purpose

Intratumoral angiogenesis quantified by microvessel density (MVD) has been shown to be a strong prognostic indicator in a number of malignant tumors. Its association with prognosis in Ewing sarcoma has not been previously studied. The aim of our study was to investigate the relationship between angiogenesis and clinical outcome in Ewing sarcoma.

Methods

Twenty-seven patients with Ewing sarcoma were included in a retrospective immunohistochemical study. Sections from diagnostic biopsies were immunostained using anti-von Willebrand factor antibody and microvessels were counted at 400× magnification on three microscopic fields per patient. Microvessel density was correlated with overall and disease-free survival as a continuous variable using univariate regression analysis and as a dichotomous variable by Kaplan-Meier and log-rank analysis. Correlation between clinicopathologic variables and the degree of angiogenesis was tested using χ² test.

Results

Increasing MVD was not confirmed to be a poor prognostic factor in univariate analysis. Also, statistically significant difference was not found in overall survival or disease-free survival between patients with high (>31.6 vessels per field) and low (≤31.6 vessels per field) microvessel counts. Finally, there was no difference regarding the metastatic rate between patients with high and low microvessel counts.

Conclusions

Our results did not confirm increasing angiogenesis quantified by MVD to be predictive of prognosis or pulmonary metastasis in Ewing sarcoma. The diffuse pattern of distribution of microvessels found in Ewing sarcoma may be responsible for the observed lack of prognostic significance of angiogenesis. Future work is required to assess the prognostic importance of MVD in this disease.     

Hematologic recovery in patients who are treated with autologous stem cells transplantation taken from bone marrow after granulocyte-colony-stimulating factor stimulation

Background

We sought to compare hematologic recovery between patients who did or did not receive granulocyte-colony-stimulating factor (G-CSF)-stimulated bone marrow (rich bone marrow [RBM]).

Materials and Methods

The study subjects were 20 patients whose bone marrow was taken without prior stimulation with G-CSF and 15 patients in whom bone marrow was taken after previous G-CSF mobilization. The bone marrow harvest took place on the fifth day after G-CSF initiation. The bone marrow aliquot was 20 mL/kg.

Results

The median value of nucleated cells obtained from patients without G-CSF preparation was 3.65 × 10⁸/kg. The median value of nucleated cells from RBM patients was 4.83 × 10⁸/kg. The median value of stem cells obtained from patients without G-CSF preparation was 0.96 × 10⁶/kg versus 1.9 × 10⁶/kg from RBM patients. The median time to recovery of the hematopoietic system based on an increase in PLT value >20 g/L was 12.6 days for RBM versus 18.8 days without G-CSF preparation. The median time to recovery of the hematopoietic system based on assessment of growth ANC>0.5 g/L was 13.0 days for RBM versus 17.8 days without G-CSF stimulation. Significantly higher values of nucleated cells and increased stem cells were observed among RBM patients compared with those whose bone marrow was harvested without any stimulation (P = .01). There was faster recovery of the hematopoietic system in cases where bone marrow was collected after G-CSF: PLT >20 g/L (P = .015) and ANC >0.5 g/L (P = .01). We also observed that the use of stimulated bone marrow shortened hospital stay after the administration of hematopoietic cells to 17.3 days compared with 23.1 days among patients receiving hematopoietic cells from nonstimulated bone marrow. The number of complications during transplantation was comparable in both cases, the most frequent ones being febrile neutropenia and grade III and IV mucositis.

Conclusion

RBM is a better method to obtain stem cells from bone marrow. Stimulated bone marrow shows faster engraftment compared with nonstimulated bone marrow helping patients who fail to generate are adequate number of stem cells from peripheral blood.     

Heterotopic heart transplantation: an expanding role in the twenty-first century?

Background

Heterotopic heart transplantation was first performed in humans in 1974, the main advantage being the continuing function of the patient's native heart, in the event of life-threatening acute rejection. The effect of cyclosporine on acute rejection saw the heterotopic transplantation technique wane. Our unit revisited heterotopic transplantation in response to a growing number of waiting list patients with high pulmonary artery pressures. We also anticipated an increased cardiac allograft utilization, and improvement of our waiting list times.

Methods

We retrospectively analyzed 151 patients undergoing heart transplantation by our unit between August 1997 and September 2003. Twenty received allografts in the heterotopic position. This cohort was compared with the 131 contemporary orthotopic heart transplant recipients with respect to their outcomes.

Results

The indication for transplantation was ischemic cardiomyopathy in 14 (70%) of the heterotopic cohort and 47 (36%) of the orthotopic cohort (p = 0.004), and dilated cardiomyopathy in 3 (15%) and 48 (37%) in the heterotopic and orthotopic groups, respectively (p = 0.06). Heterotopic recipients were significantly older than orthotopic recipients, and they had higher pulmonary artery pressures. The heterotopic donors were also older and the ischemic times were longer. A subgroup analysis was made among those patients who had high pulmonary artery pressures as these groups were better matched. Major morbidity in the heterotopic heart transplantation group consisted of reversible allograft dysfunction in 4 patients, renal dysfunction requiring hemofiltration in 3 patients, profound myopathy in 4 patients, and cerebrovascular events in 2 patients. There were two early deaths in the heterotopic transplant group and eight in the orthotopic group (p = 0.87). Kaplan-Meier survival analysis of survival was performed.

Conclusions

Heterotopic heart transplantation is a viable transplant option for selected high-risk heart transplant recipients in spite of somewhat poorer outcomes.     

Size does matter-donor-to-recipient body mass index difference may affect renal graft outcome

Background

Obesity, in the either kidney donor or the recipient, has been related to worse graft function. The aim of this study was to compare long-term graft outcomes of living-related kidney recipients regarding the donor-to-recipient body mass index (BMI) ratio.

Methods

From November 2002 to November 2010, 62 consecutive living-related kidney transplantations were performed at our center. Donor and recipient BMIs were categorized by Taiwan's national standard using dividing values of 18.5, 24, and 27 kg/m² to divide subjects into donor-to-recipient BMI categories. These with the same BMI category as their donors were defined as the same-BMI group (group 0); recipients with a lower BMI category than their donors were defined as the large-to-small group (group 1); and those with a higher BMI category than their donors were defined as the small-to-large group (group 2). Baseline parameters and posttransplantation follow-up data were analyzed according to this grouping.

Results

Of the 57 recipients followed regularly at our hospital (mean follow-up 48.9 months), 21 (36.8.1%) were in group 0; 26 (45.6%) in group 1, and 10 (17.6%) in group 2. The baseline parameters were similar among these groups. The overall graft survival rates were 81.0% in group 0, 76.9% in group 1, and 90.0% in group 2. The rejection-free graft survival rates were 81.0%, 65.4%, and 90.0%, respectively. By Kaplan-Meier analysis, group 1 showed worse rejection-free graft survival than group 0 or group 2 (log-rank P = .046).

Conclusions

Living-related recipients of kidneys from donors with a higher BMI showed lower long-term graft survival, which might suggest that petite recipients may need time to compensate adequate blood flow for the relative large graft, thus carrying a higher chance of rejection and worse graft outcomes.     

A 6-Month, Multicenter, Single-Arm Pilot Study to Evaluate the Efficacy and Safety of Generic Tacrolimus (TacroBell) After Primary Renal Transplantation

Objective

Tacrolimus has been shown to be an important immunosuppressive agent in organ and bone marrow transplantation. Previously, we reported that there were no statistically significant differences between the pharmacokinetic parameters of the oral formulation of generic tacrolimus (TacroBell) and the conventional formulation (Prograf). This study was designed to evaluate the efficacy and safety of oral capsules of TacroBell in de novo renal transplantation.

Methods

Ninety-six renal transplant recipients from 9 transplantation centers in South Korea were enrolled between November 2005 and July 2007. De novo renal recipients ranged from 19-65 years old. Ninety-four patients who underwent renal transplantation were administered study drug at least one time in the intent-to-treat (ITT) analysis. This phase 4 clinical trial was a 26-week, open-label, noncomparative, multicenter study.

Results

An acute rejection episode developed in 10/94 recipients (10.6%, 95% confidence interval, 4.4%-16.9%). There were no patient deaths during the study. The 6-month graft survival rate was 96.8%.

Conclusion

Based on this study, treatment with TacroBell is considered to be efficient and safe after primary renal transplantation.     

The expression and distribution of xenogeneic targeted antigens on porcine bone tissue

Objective

The objective of this study was to investigate the distribution of α-galactosyl (α-Gal), major histocompatibility complex (MHC)-I, and MHC-II antigens on adult porcine bone tissue.

Methods

Distribution of α-Gal, MHC-I, and MHC-II antigens on porcine bone tissue were observed using immunohistochemistry.

Results

α-Gal, MHC-I xenogeneic antigens were extensively observed on the surface of bone marrow cells, osteocytes, osteoblasts, and Harversian canals; MHC-II antigens were mainly expressed on bone marrow cells.

Conclusion

α-Gal, MHC-I, and MHC-II are the main xenogeneic antigens that must be deleted to avoid xenogeneic immune reactions against bone xenografts.     

Deceased Donor Kidney Transplantation in Elderly Patients: Is There a Difference in Outcomes?

Introduction

There is a paucity of data on long-term outcomes of older kidney recipients. Our aim was to compare the early and long-term outcomes of deceased donor kidney transplantation in patients aged ≥60 years with outcomes in younger recipients.

Materials and Methods

From 1998 to 2005, we performed 271 deceased donor kidney transplants. There were 76 recepients (28.1%) >60 years old. Older candidates were carefully selected based on their physiologic, cardiac, and performance status. Demographic data, including clinical characteristics, early complications, mortality, and patient and graft survival rates, were collected and analyzed.

Results

Older patients had comparable perioperative mortality and morbidity, incidence of delayed graft function (DGF), length of stay, and readmissions compared with younger patients. The rates of acute rejection and major infections were also comparable between the 2 study groups. Among older recipients, 25/76 (32.1%) patients received extended criteria donor kidneys compared with only 35/195 (17.9%) of younger patients (P < .001). Nevertheless, equivalent 1-, 3-, and 5-year allograft survival rates were observed in elderly and young patients; 91.5% versus, 92.5%, 78.5% versus 81.9%, and 75.6% versus 78.5%, respectively. Overall patient survival was also comparable in both groups.

Conclusion

Kidney transplantation in appropriately selected elderly recipients provides equivalent outcomes compared with those observed in younger patients. These observations support the notion that older recipients should not lose access to deceased donor kidney transplantation in the effort to achieve a perceived gain in social utility.     

Watson fundoplication in children: a comparative study with Nissen fundoplication

Background

Nissen fundoplication is the gold standard antireflux procedure in children. In 1996, one pediatric surgeon adopted the anterior fundoplication described by Watson in 1991. This procedure is reported to achieve good reflux control while permitting burping, active vomiting, and reducing gas bloat. An audit project was undertaken to compare the clinical outcome of children undergoing Nissen and Watson fundoplication.

Methods

The case notes of 144 children undergoing open fundoplication between February 1995 and February 2002 were reviewed retrospectively.

Results

Results of 72 boys and 59 girls comprising 76 Nissen and 55 Watson fundoplications were assessed. In each group, one death occurred within 1 month of operation. Chest infections occurred in 6.6% (Nissen) and 1.8% (Watson), and wound infections in 2.6% and 1.8%, respectively. Dysphagia was recorded in 7.9% of Nissen and 1.8% of Watson fundoplications. Follow-up data were analyzed in 70 children with Nissen and 48 children with Watson fundoplication. When overall clinical outcome was assessed for those patients with a minimum follow-up of 1 year, 85.1% Nissen and 88.2% Watson were judged good/excellent; 14.9% Nissen and 11.8% Watson were judged poor/bad.

Conclusion

Watson fundoplication can safely be performed in children with comparable clinical outcome to Nissen fundoplication.     

Caecal volvulus

Background

Caecal volvulus accounts for 30% of all cases of volvulus of the colon.

Methods

We recorded clinical data and accurate images of volvulus of the cecum.

Results

A detorsion with resection and primary anastomosis was performed. We reviewed the management and surgical strategies for cecal volvulus.

Conclusions

Caecal volvulus is an uncommon entity with potentially severe outcomes and requires surgical management.