Renzo Cecere

Clostridium difficile colitis: Increasing incidence, risk factors, and outcomes in solid organ transplant recipients

Background Clostridium difficile-associated diarrhea (CDAD) is an increasingly important diagnosis in solid organ transplant recipients, with rising incidence and mortality. We describe the incidence, risk factors, and outcomes of colectomy for CDAD after solid organ transplantation. Methods Patients with CDAD were identified from a prospective transplant database. Complicated Clostridium difficile colitis (CCDC) was defined as CDAD associated with graft loss, total colectomy, or death. Results From 1999 to 2010, we performed solid organ transplants for 1331 recipients at our institution. The incidence of CDAD was 12.4% (165 patients); it increased from 4.5% (1999) to 21.1% (2005) and finally 9.5% (2010). The peak frequency of CDAD was between 6 and 10 days posttransplantation. Age more than 55 years (hazard ratio [HR]: 1.47, 95% confidence interval [CI]=1.16–1.81), induction with antithymocyte globulin (HR: 1.43, 95% CI=1.075–1.94), and transplant other than kidney alone (liver, heart, pancreas, or combined kidney organ) (HR: 1.41, 95% CI=1.05–1.92) were significant independent risk factors for CDAD. CCDC occurred in 15.8% of CDAD cases. Independent predictors of CCDC were white blood cell count more than 25,000/&mgr;L (HR: 1.08, 95% CI=1.025–1.15) and evidence of pancolitis on computed tomography scan (HR: 2.52, 95% CI=1.195–5.35). Six patients with CCDC underwent colectomy with 83% patient survival and 20% graft loss. Of the medically treated patients with CCDC (n=20), the patient survival was 35% with 100% graft loss. Conclusions We have identified significant risk factors for CDAD and predictors of progression to CCDC. Furthermore, we found that colectomy can be performed with excellent survival in selected patients.

One-stage midline unifocalization and complete repair in infancy versus multiple-stage unifocalization followed by repair for complex heart disease with major aortopulmonary collaterals

BACKGROUND Patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries have traditionally required multiple unifocalization staging operations before undergoing complete repair. Recently, the feasibility of a single-stage unifocalization and repair was demonstrated by Hanley. In this report, we describe our experience with each approach. METHODS AND RESULTS Since 1989, 11 of 12 patients with pulmonary atresia, ventricular septal defect, and major aortopulmonary collateral arteries have undergone complete surgical correction. The first seven patients were subjected to staged bilateral unifocalizations, with repair being achieved in six (group I). The last five patients have undergone a single-stage midline unifocalization and repair via a sternotomy (group II). Four of these were infants (2 weeks to 9 months) and one was 13 years old. All patients in group I had tetralogy of Fallot, whereas in group II three patients had tetralogy of Fallot, one patient had double-outlet right ventricle, and one patient had complete atrioventricular canal and transposition. In group I, the median age at the first operation was 43 weeks. Complete repair was performed at a median age of 3.5 years, with a mean number of 3.3 operations required. In group II, only one operation was required to achieve complete repair at a median age of 28 weeks. The postoperative right ventricular/left ventricular pressure ratio was 0.49 in group I and 0.45 in group II. One intraoperative death and one late death occurred in group I and no early or late deaths in group II. Currently, four patients in group I and all five patients in group II are alive and well. CONCLUSIONS Early intervention with both surgical approaches can lead to complete biventricular repair in most patients. Because the single-stage midline unifocalization and repair can achieve a completely repaired heart in infancy with one operation, it is currently our approach of choice.

Discretely Loaded Beam-Type Optical Fiber Tactile Sensor for Tissue Manipulation and Palpation in Minimally Invasive Robotic Surgery

In traditional open surgery, surgeons use their fingertip palpation to investigate the hidden anatomical structures of tissue. However, in the current commercially available minimally invasive robotic surgery (MIRS) systems, while surgical instruments interact with tissues, surgeons do not sense any tactile information. Therefore, tactile sensors are required to be integrated into the tips of surgical instruments to mimic the perception of the surgeons fingertips. The electrically based tactile sensors that exist at present cannot usually operate under static loading conditions. In addition, they are not compatible with magnetic resonance imaging (MRI) devices. Therefore, this research was aimed at restoring tactile information by developing an MRI compatible optical fiber tactile sensor. The sensor consists of only one single moving part. Thanks to this novel design, the sensor does not require the use of an array of sensors to measure the distributed tactile information. This capability simplifies the integration of the sensor into any suitable space available at the tips of surgical instruments. In addition, the sensor performs under both static and dynamic loading conditions. A theoretical model of the sensor and a finite-element model of the sensor-tissue interaction were developed. To validate the sensor, a prototype of the sensor was fabricated and tested.

Cardiac Surgery in Octogenarians: Long-Term Survival, Functional Status, Living Arrangements, and Leisure Activities

BACKGROUND A prospective study of survival, functional outcome, living arrangements, daily activities and leisure engagements among octogenarians up to 5 years after cardiac surgery was performed. METHODS The study consisted of a cohort of 300 consecutive octogenarians with three interviews made at 6-month intervals for a total of 593 postoperative interviews. Functional outcomes were measured using the Barthel index and Karnofsky performance scores and divided into autonomous, semiautonomous, or dependent. Living arrangements and leisure activities within the social, physical, cognitive, and creative domains were recorded in an open-ended questionnaire. RESULTS There were 150 men and 150 women with a mean age 82.6 years. The 30-day survival was 84.3%. Actuarial survival at 1, 3, and 5 years was 76.6%, 66.6%, and 57.8%, respectively. Among the survivors at the first interview, 2.2 years postoperatively, there were 63.9% autonomous, 31.7% semiautonomous, and 4.3% dependent patients versus at the last interview, 3.6 years postoperatively, in which there were 64.9% autonomous, 28.1% semiautonomous, and 9.2% dependent. At the first interview, 76.4% were at home, 19.2 % in a residence, and 4.3% in a supervised setting. At the third interview, 71.8% were at home, 21.2% in a residence, and 6.9% in a supervised setting. Nearly all patients were involved in leisure activities in the social (98.9%), cognitive (98.4%), and physical (93.1%) domains. At the end of the last interview, activities within the social and cognitive domains were maintained with a small decrease in the physical domain. CONCLUSIONS Surviving octogenarians remain at home, function independently, and engage in regular leisure activities years after cardiac surgery. This information might help physicians and surgeons regarding long-term outcome of open cardiac surgery in octogenarians.

Anti-CD25 monoclonal antibody coverage allows for calcineurin inhibitor "holiday" in solid organ transplant patients with acute renal dysfunction.

Background. Solid organ transplant (Tx) patients on calcineurin inhibitors (CNI) can develop acute renal dysfunction (ARD), which could be improved by reducing or withholding (“holiday”) CNI dose. Methods. We used anti-CD25 monoclonal antibodies to prevent acute rejection in 11 adult Tx patients (7 heart, 2 liver, 2 heart-renal Tx), requiring a CNI “holiday” because of 15 events of ARD after the initial postTx hospitalization. An event of ARD was defined as an increase in serum creatinine (Scr)>25% vs. baseline. The CNI “holiday” was implemented until Scr had decreased to baseline. Basiliximab was used in 7 patients (11 events), and daclizumab was used in 4 patients (4 events). Results. The CNI “holiday” was implemented over 21±51 days. Anti-CD25 mAb were well tolerated with no episodes of acute rejection. Scr (&mgr;mol/liter) increased from 145±48 to 301±92 (P <0.0001), and decreased to 143±55 with the CNI “holiday.” Conclusions. Our results suggest that a CNI “holiday” may improve ARD after solid organ Tx without rejection under anti-CD25 mAb coverage.

The Impella® LP 5.0 as a bridge to long-term circulatory support

Multi-organ failure (MOF) secondary to bi-ventricular cardiac dysfunction is a major therapeutic challenge. In addition to aggressive medical therapy, it frequently requires circulatory support with uni- or bi-ventricular assist devices. The Impella LP 5.0 is a new microaxial left ventricular assist device (LVAD). Microaxial LVADs have been used for short-term circulatory support in patients with cardiogenic shock due to myocarditis, post coronary artery bypass grafting (CABG), or during high-risk percutaneous coronary interventions (PCI). We present a case of a patient in bi-ventricular failure successfully bridged to permanent circulatory support. Relative merits of this therapeutic approach are outlined and discussed.

Canadian Cardiovascular Society Consensus Conference update on cardiac transplantation 2008: Executive Summary

The Canadian Cardiovascular Society published its Consensus Conference on cardiac transplantation in 2003 (1). The present Executive Summary provides an update on the previous document, with a focus on new evidence and significant changes in our understanding of relevant issues and management of cardiac transplantation. The standard guidelines used in these recommendations are shown in Table 1. TABLE 1 Guidelines on recommendations: Levels of evidence

The Clinical Impact of an Early Decline in Kidney Function in Patients Following Heart Transplantation

Renal dysfunction is a well‐known complication following heart transplantation. We examined an early decline in kidney function as a predictor of progression to end‐stage renal disease and mortality in heart transplant recipients. We performed a retrospective cohort study of 233 patients who received a heart transplant between July 1985 and July 2004, and who survived >1 month. The decline in estimated creatinine clearance (CrCl) was used to predict the outcomes of need for chronic dialysis or mortality >1‐year posttransplant. The earliest time to chronic dialysis was 484 days. A 30% decline in CrCl between 1 month and 12 months predicted the need for chronic dialysis (p = 0.01), all‐cause mortality (p < 0.0001) and time to first CrCl ≤30 mL/min at >1‐year posttransplant (p = 0.02). A 30% decline in CrCl between 1 month and 3 months also independently predicted the need for chronic dialysis (p = 0.04) and time to first CrCl ≤ 30 mL/min at >1‐year posttransplant (p = 0.01). In conclusion, an early drop in CrCl within the first year is a strong predictor of chronic dialysis and death >1‐year postheart transplantation. Future studies should focus on kidney function preservation in those identified at high risk for progression to end‐stage kidney disease and mortality.

Impact of cyclosporine 2‐h level and mycophenolate mofetil dose on clinical outcomes in de novo heart transplant patients receiving anti‐thymocyte globulin induction

Abstract: Background: Cyclosporine (CsA) 2‐h post‐dose level (C2) correlates better than trough levels (C0) with the area under the curve. We evaluated the clinical impact of C2 and mycophenolate mofetil (MMF) dose in adult heart transplant patients receiving anti‐thymocyte globulin (ATG) induction.

Hyaluronic acid-based hydrogel induces neovascularization and improves cardiac function in a rat model of myocardial infarction

OBJECTIVES The use of stem cells in cardiac regeneration is still limited due to low cellular integration and engraftment rates. Consequently, there has been a spurt in research on developing alternative regenerative therapies. Hyaluronic acid (HA) is a major component of the extracellular matrix that is non-immunogenic, and has been implicated in various wound-healing functions such as angiogenesis and inflammation modulation, making it an ideal candidate for regenerative biomaterials. In this study, we examine the potential of acellular hyaluronic acid-based hydrogel in improving cardiac function post-myocardial infarction in a rat model. METHODS Hyaluronic acid-based hydrogel was injected into the peri-infarct region post-myocardial infarction induction in Lewis rats. Cardiac function in control (n = 10) and gel-injected groups (n = 10) was evaluated up to 4 weeks post-myocardial infarction. Evaluation of cardiac function was conducted using transthoracic echocardiography. Histological analysis of scar area was evaluated via haematoxylin and eosin (H & E), and Sirius red staining. Neovascularization was detected using vascular endothelial growth factor (VEGF) staining. RESULTS Evaluation of cardiac function using transthoracic echocardiography revealed a 18.2% (P < 0.01) increase in ejection fraction in gel-injected groups when compared with the control group, almost returning the ejection fraction to baseline levels (preop). Histological analysis of scar area by haematoxylin and eosin (H&E), and Sirius red staining demonstrated decreased scarring, and a 22.6% (P < 0.01) decrease in collagen deposition in the gel-injected group compared with the control group. VEGF staining indicated a significant increase in novel vasculature formation in hydrogel-injected groups when compared with control. CONCLUSIONS Due to its regenerative potential, hyaluronic acid-based hydrogel provides a promising novel therapy to be used alone, or as a scaffold delivering a variety of drugs or cells to combat heart disease in a multifaceted approach.