Elliott D. Kozin

Risk Score Derived from Pre-operative Data Analysis Predicts the Need for Biventricular Mechanical Circulatory Support

BACKGROUND Right ventricular (RV) failure after left ventricular assist device (LVAD) placement is a serious complication and is difficult to predict. In the era of destination therapy and the total artificial heart, predicting post-LVAD RV failure requiring mechanical support is extremely important. METHODS We reviewed patient characteristics, laboratory values and hemodynamic data from 266 patients who underwent LVAD placement at the University of Pennsylvania from April 1995 to June 2007. RESULTS Of 266 LVAD recipients, 99 required RV assist device (BiVAD) placement (37%). We compared 36 parameters between LVAD (n = 167) and BiVAD patients (n = 99) to determine pre-operative risk factors for RV assist device (RVAD) need. By univariate analysis, 23 variables showed statistically significant differences between the two groups (p < or = 0.05). By multivariate logistic regression, cardiac index < or =2.2 liters/min/m(2) (odds ratio [OR] 5.7), RV stroke work index < or =0.25 mm Hg . liter/m(2) (OR 5.1), severe pre-operative RV dysfunction (OR 5.0), pre-operative creatinine > or =1.9 mg/dl (OR 4.8), previous cardiac surgery (OR 4.5) and systolic blood pressure < or =96 mm Hg (OR 2.9) were the best predictors of RVAD need. CONCLUSIONS The most significant predictors for RVAD need were cardiac index, RV stroke work index, severe pre-operative RV dysfunction, creatinine, previous cardiac surgery and systolic blood pressure. Using these data, we constructed an algorithm that can predict which LVAD patients will require RVAD with >80% sensitivity and specificity.

Early planned institution of biventricular mechanical circulatory support results in improved outcomes compared with delayed conversion of a left ventricular assist device to a biventricular assist device

OBJECTIVE It is generally accepted that patients who require biventricular assist device support have poorer outcomes than those requiring isolated left ventricular assist device support. However, it is unknown how the timing of biventricular assist device insertion affects outcomes. We hypothesized that planned biventricular assist device insertion improves survival compared with delayed conversion of left ventricular assist device support to biventricular assist device support. METHODS We reviewed and compared outcomes of 266 patients undergoing left ventricular assist device or biventricular assist device placement at the University of Pennsylvania from April 1995 to June 2007. We subdivided patients receiving biventricular assist devices into planned biventricular assist device (P-BiVAD) and delayed biventricular assist device (D-BiVAD) groups based on the timing of right ventricular assist device insertion. We defined the D-BiVAD group as any failure of isolated left ventricular assist device support. RESULTS Of 266 patients who received left ventricular assist devices, 99 (37%) required biventricular assist device support. We compared preoperative characteristics, successful bridging to transplantation, survival to hospital discharge, and Kaplan-Meier 1-year survival between the P-BiVAD (n = 71) and D-BiVAD (n = 28) groups. Preoperative comparison showed that patients who ultimately require biventricular support have similar preoperative status. Left ventricular assist device (n = 167) outcomes in all categories exceeded both P-BiVAD and D-BiVAD group outcomes. Furthermore, patients in the P-BiVAD group had superior survival to discharge than patients in the D-BiVAD group (51% vs 29%, P < .05). One-year and long-term Kaplan-Meier survival distribution confirmed this finding. There was also a trend toward improved bridging to transplantation in the P-BiVAD (n = 55) versus D-BiVAD (n = 22) groups (65% vs 45%, P = .10). CONCLUSION When patients at high risk for failure of isolated left ventricular assist device support are identified, proceeding directly to biventricular assist device implantation is advised because early institution of biventricular support results in dramatic improvement in survival.

NMII Forms a Contractile Transcellular Sarcomeric Network to Regulate Apical Cell Junctions and Tissue Geometry

Nonmuscle myosin II (NMII) is thought to be the master integrator of force within epithelial apical junctions, mediating epithelial tissue morphogenesis and tensional homeostasis. Mutations in NMII are associated with a number of diseases due to failures in cell-cell adhesion. However, the organization and the precise mechanism by which NMII generates and responds to tension along the intercellular junctional line are still not known. We discovered that periodic assemblies of bipolar NMII filaments interlace with perijunctional actin and α-actinin to form a continuous belt of muscle-like sarcomeric units (∼400-600 nm) around each epithelial cell. Remarkably, the sarcomeres of adjacent cells are precisely paired across the junctional line, forming an integrated, transcellular contractile network. The contraction/relaxation of paired sarcomeres concomitantly impacts changes in apical cell shape and tissue geometry. We show differential distribution of NMII isoforms across heterotypic junctions and evidence for compensation between isoforms. Our results provide a model for how NMII force generation is effected along the junctional perimeter of each cell and communicated across neighboring cells in the epithelial organization. The sarcomeric network also provides a well-defined target to investigate the multiple roles of NMII in junctional homeostasis as well as in development and disease.

Permissive environment in postnatal wounds induced by adenoviral-mediated overexpression of the anti-inflammatory cytokine interleukin-10 prevents scar formation

Wound healing in the mid‐gestation fetus is scarless with minimal inflammation and a unique extracellular matrix. We have previously documented the relative lack of inflammatory cytokines in this environment. We demonstrate that interleukin (IL)‐10 is highly expressed in mid‐gestation human fetal skin but is absent in postnatal human skin. We hypothesize that overexpression of IL‐10 in postnatal skin may replicate a permissive environment for scarless healing. To study the mechanism underlying this process we performed immunohistochemistry for IL‐10 in human mid‐gestation fetal and postnatal skin. We also determined if adenoviral‐mediated overexpression of IL‐10 could allow for scarless wound healing in a murine incisional wound model. Wounds were analyzed at 1–90 days postwounding for effects on scar formation, inflammatory response, and biomechanical properties. Ad‐IL‐10 reconstitutes a permissive environment for scarless healing as shown by reconstitution of a normal dermal reticular collagen pattern and distribution of dermal elements. Compared with controls, Ad‐IL‐10 treated wounds showed reduced inflammatory response and no difference in biomechanical parameters. Therefore, overexpression of IL‐10 in postnatal wounds results in a permissive environment for scarless wound repair, possibly by replicating a fetal wound environment.

Mammary analogue secretory carcinoma: Update on a new diagnosis of salivary gland malignancy

To review the known histopathologic findings and clinical behavior of mammary analogue secretory carcinoma (MASC).

Thermal effects of endoscopy in a human temporal bone model: Implications for endoscopic ear surgery

Although the theoretical risk of elevated temperatures during endoscopic ear surgery has been reported previously, neither temperature change nor heat distribution associated with the endoscope has been quantified. In this study, we measure temperature changes during rigid middle ear endoscopy in a human temporal bone model and investigate whether suction can act as a significant cooling mechanism.

Systematic review of outcomes following observational and operative endoscopic middle ear surgery.

Middle ear surgery increasingly employs endoscopes as an adjunct to or replacement for the operative microscope. We provide a systematic review of endoscope applications in middle ear surgery with an emphasis on outcomes, including the need for conversion to microscope, audiometric findings, length of follow‐up, as well as disease‐specific outcomes.

Pediatric endoscopic ear surgery in clinical practice: Lessons learned and early outcomes

Only a few reports describe the outcomes following endoscopic ear surgery (EES) in children for chronic ear disease. We differentiate between transcanal endoscopic ear surgery (TEES), where the case is performed with only endoscopic visualization, from non‐TEES, where the endoscope is not used at all or used as an adjunct to the microscope. We hypothesize that EES is an effective approach to manage middle ear pathology using a transcanal approach in most cases, and can be incorporated into a pediatric otology practice with a neutral or positive effect on outcomes. Lessons learned during this process are analyzed and discussed.

Effects of sirolimus vs. calcineurin inhibitors on renal dysfunction after orthotopic liver transplantation

Abstract:  Small uncontrolled series have suggested that sirolimus favorably impacts renal function after orthotopic liver transplantation (OLT). We sought to retrospectively compare renal dysfunction between cohorts exposed to sirolimus‐based and calcineurin inhibitor‐based immunosuppression. We retrospectively studied 79 patients converted to sirolimus‐based immunosuppression and 100 control subjects continued on calcineurin inhibitor‐based immunosuppression after OLT at our institution from 2000 to 2005. We collected clinical, demographic, and medication history. Renal dysfunction was defined as two or more wk of creatinine ≥2.0 mg/dL. Cohorts were compared using Kaplan–Meier survival analysis and Cox proportional hazards modeling. Patients began sirolimus a median 83 d post‐OLT and were followed on the medication for median 359 d. Patients in both the sirolimus and calcineurin inhibitor cohorts had median creatinine 1.2 mg/dL at study entry. Sirolimus‐based immunosuppression was associated with a 1.8 (0.8–4.3, p = 0.17) hazards ratio for renal dysfunction. Adjusting for presence of hepatocellular carcinoma, combined kidney/liver transplantation, and age, the hazards ratio was 2.0 (0.8–4.8, p = 0.13). These point estimates were not substantially altered after subgroup analysis of sirolimus as the lone immunosuppressant, duration of exposure, and time between OLT and sirolimus conversion. In conclusion, our retrospective, controlled study showed that conversion to sirolimus after OLT did not protect against renal dysfunction. The effect of sirolimus on renal function will need to be prospectively evaluated in a prospective, randomized trial.

Off‐pump, minimally invasive and robotic coronary revascularization yield improved outcomes over traditional on‐pump CABG

Coronary artery disease is a global health concern, with increasing morbidity and mortality. Surgical coronary artery bypass grafting has been performed on cardiopulmonary bypass for nearly four decades, with excellent long‐term durability. Beating‐heart coronary surgery has been increasing in frequency in an attempt to decrease cardiopulmonary bypass‐related morbidity. Furthermore, with increasing expertise and technology, minimally invasive and robotic techniques have been developed to enhance post‐operative recovery, patient satisfaction and cosmesis. Several clinical trials have demonstrated decreased morbidity and more rapid recovery following off‐pump, minimally invasive and robotic procedures when compared to on‐pump coronary artery bypass grafts (CABGs). An equivalent extent of revascularization and medium‐term anastomotic patency has been demonstrated among all approaches. Furthermore, for a large number of patients who do not have anatomy amenable to traditional coronary revascularization, adjunctive molecular therapies may provide alternative myocardial micro‐revascularization. Copyright