Zain Khalpey

Conformal piezoelectric energy harvesting and storage from motions of the heart, lung, and diaphragm

Significance Heart rate monitors, pacemakers, cardioverter-defibrillators, and neural stimulators constitute broad classes of electronic implants that rely on battery power for operation. Means for harvesting power directly from natural processes of the body represent attractive alternatives for these and future types of biomedical devices. Here we demonstrate a complete, flexible, and integrated system that is capable of harvesting and storing energy from the natural contractile and relaxation motions of the heart, lung, and diaphragm at levels that meet requirements for practical applications. Systematic experimental evaluations in large animal models and quantitatively accurate computational models reveal the fundamental modes of operation and establish routes for further improvements. Here, we report advanced materials and devices that enable high-efficiency mechanical-to-electrical energy conversion from the natural contractile and relaxation motions of the heart, lung, and diaphragm, demonstrated in several different animal models, each of which has organs with sizes that approach human scales. A cointegrated collection of such energy-harvesting elements with rectifiers and microbatteries provides an entire flexible system, capable of viable integration with the beating heart via medical sutures and operation with efficiencies of ∼2%. Additional experiments, computational models, and results in multilayer configurations capture the key behaviors, illuminate essential design aspects, and offer sufficient power outputs for operation of pacemakers, with or without battery assist.

Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery.

Objective:Evaluate the association of perioperative hyperglycemia and postoperative infections (POI) in patients who had undergone general surgery. Background:Intensive glucose control leads to less postoperative infections (POI) in critically ill surgical patients, but the relationship of hyperglycemia and POI in a general surgical population remains unknown. Methods:A retrospective study of 995 patients who had undergone general and vascular surgery investigated the association of perioperative acute hyperglycemia and risk of 30-day POI over an 18-month period. The primary predictor of interest was postoperative glucose (POG). Bivariate analyses determined the association of each independent variable with POI. Factors significant at P < 0.05 were used in multivariable logistic regression models. Results:In bivariate analyses, preoperative blood glucose (P = 0.012), POG (P = 0.009), age (P = 0.002), diabetes (P = 0.04), American Society of Anesthesia Classification (ASAC) (P < 0.0001), operation length (P = 0.02), and blood transfusions (P = 0.02) were significant predictors of POI. In multivariate analyses, only POG (OR = 1.3, (1.03–1.64)), ASAC (OR = 1.9, (1.31–2.83)), and emergency status (OR = 2.2, (1.21–3.80)) remained significant predictors of POI. Postoperative hyperglycemia increased the risk of POI by 30% with every 40-point increase from normoglycemia (<110 mg/dL). Longer hospitalization was also observed for patients with POG from 110 to 200 mg/dL (OR = 1.4, (1.1–1.7)) and >200 mg/dL (OR = 1.8, (1.4–2.5)). Conclusion:The increased risk of POI and length of hospitalization posed by postoperative hyperglycemia is independent of diabetic status and needs further evaluation to assess for possible benefits of postoperative glycemic control in patients who have undergone general surgery.

Prevalence and variability of internal mammary artery graft use in contemporary multivessel coronary artery bypass graft surgery: analysis of the Society of Thoracic Surgeons National Cardiac Database.

Background— Use of an internal mammary artery (IMA) is a well-recognized, nationally endorsed quality indicator for evaluating the process of operative care for coronary artery bypass graft surgery. An objective assessment of the current status of IMA use has not been systematically performed. Methods and Results— This cross-sectional observational study analyzed data on 541 368 coronary artery bypass graft surgery procedures reported by 745 hospitals in the Society of Thoracic Surgeons National Cardiac Database from 2002 through 2005. We assessed the current status of IMA use, the association of hospital volume and IMA use, and disparities in IMA use by patient gender and race and by region of hospital location. Rates of using at least 1 IMA and bilateral IMA were 92.4% and 4.0%, with increasing trends over the years. Hospital volume was not significantly associated with IMA use. IMAs were used less frequently in women than men (for at least 1 IMA: odds ratio, 0.62; 95% confidence interval, 0.61 to 0.63; for bilateral IMA: odds ratio, 0.65; 95% confidence interval, 0.63 to 0.68) and less frequently in nonwhite patients than white patients (for at least 1 IMA: odds ratio, 0.84; 95% confidence interval, 0.81 to 0.87; for bilateral IMA: odds ratio, 0.79; 95% confidence interval, 0.75 to 0.83). There were significant differences in frequency of IMA use by hospital region. Conclusions— Frequency of IMA use in coronary artery bypass graft surgery is increasing; however, many patients still do not receive the benefits of IMA grafts, and some hospitals have a very low IMA use rate. Hospital volume is not associated with IMA use in coronary artery bypass graft surgery. Analysis of this critical performance measure reveals significant gender and race disparities.

Conversion to Sirolimus as Primary Immunosuppression Attenuates the Progression of Allograft Vasculopathy After Cardiac Transplantation

Background— We investigated the potential of conversion to sirolimus (SRL) as a primary immunosuppressant in attenuating cardiac allograft vasculopathy progression. Methods and Results— Twenty-nine cardiac transplant recipients were converted to SRL 3.8±3.4 years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. Secondary immunosuppressants (azathioprine or mycophenolate) and steroids remained unchanged. Forty patients (controls) 4.8±4.0 years from transplantation were maintained on CNIs. Three-dimensional intravascular ultrasound studies were performed at baseline and 12.1±2.6 months later. Mean plaque (media and intima) volume (PV) and plaque index (PI) (PV/vessel volume percent) increased significantly in the CNI group (1.28±2.86 mm3/mm, P=0.004; and 6±8%, P=0.0001) but not in the SRL group (0.1±1.13 mm3/mm, P=0.63; and 0.1±8%, P=0.94). In patients enrolled within 2 years after transplantation, the increases in PV (0.06±1.06 versus 1.77±1.65 mm3/mm; P=0.0081) and PI (0±9% versus 10±8%; P=0.0145) were smaller in the SRL group (n=11) than in the CNI (n=12) group. In patients enrolled ≥2 years after transplantation, the increase in PI was less in the SRL group compared with the CNI group (0.1±6.5% versus 5±8%; P=0.033), but changes in PV did not differ significantly. Treatment with azathioprine or mycophenolate did not affect PV or PI in either the SRL group (PV: 0.22±0.66 versus 0.05±1.45 mm3/mm, P=0.46; PI: 1.5±6% versus −1.6±8.5%, P=0.29) or the CNI group (PV: 1.42±1.39 versus 1.06±2.28 mm3/mm, P=0.49; PI: 7.8±8.7% versus 4.8±7.3%, P=0.23). Conclusions— Substituting CNI with SRL as primary immunosuppression attenuates cardiac allograft vasculopathy progression.

Accommodation: Preventing Injury in Transplantation and Disease

Humoral immunity, as a cause of damage to blood vessels, poses a major barrier to successful transplantation of organs. Under some conditions, humoral immunity causes little or no damage to an organ graft. We have referred to this condition, in which a vascularized graft functions in the face of humoral immunity directed against it, as “accommodation.” In this paper, we review changes in the graft and in the host that may account for accommodation, and we consider that what we call accommodation of organ grafts may occur widely in the context of immune responses, enabling immune responses to target infectious organisms without harming self-tissues.

Survival Benefit of Solid-Organ Transplant in the United States

IMPORTANCE The field of transplantation has made tremendous progress since the first successful kidney transplant in 1954. OBJECTIVE To determine the survival benefit of solid-organ transplant as recorded during a 25-year study period in the United Network for Organ Sharing (UNOS) database and the Social Security Administration Death Master File. DESIGN, SETTING, AND PARTICIPANTS In this retrospective analysis of UNOS data for solid-organ transplant during a 25-year period (September 1, 1987, through December 31, 2012), we reviewed the records of 1,112,835 patients: 533,329 recipients who underwent a transplant and 579 506 patients who were placed on the waiting list but did not undergo a transplant. MAIN OUTCOMES AND MEASURES The primary outcome was patient death while on the waiting list or after transplant. Kaplan-Meier survival functions were used for time-to-event analysis. RESULTS We found that 2,270,859 life-years (2,150,200 life-years from the matched analysis) were saved to date during the 25 years of solid-organ transplant. A mean of 4.3 life-years were saved (observed to date) per solid-organ transplant recipient. Kidney transplant saved 1,372,969 life-years; liver transplant, 465,296 life-years; heart transplant, 269,715 life-years; lung transplant, 64,575 life-years; pancreas-kidney transplant, 79,198 life-years; pancreas transplant, 14,903 life-years; and intestine transplant, 4402 life-years. CONCLUSIONS AND RELEVANCE Our analysis demonstrated that more than 2 million life-years were saved to date by solid-organ transplants during a 25-year study period. Transplants should be supported and organ donation encouraged.

Replacement of calcineurin-inhibitors with sirolimus as primary immunosuppression in stable cardiac transplant recipients

Background. Calcineurin-inhibitor (CNI) nephrotoxicity is a major cause of morbidity and mortality after cardiac transplantation. The aim of this study was to assess over 2 years the safety and effect on renal function of withdrawal of CNI immunosuppression and replacement with sirolimus (SRL) in stable cardiac transplant recipients. Methods. CNI was substituted with SRL in 78 cardiac transplant recipients (SRL group) of whom 58 (group A) had CNI-induced renal impairment (glomerular filtration rate [GFR] <50 mL/min) and 20 (group B) had preserved renal function (GFR >50 mL/min). Fifty-one patients (CNI group) with renal impairment (GFR ≤50 mL/min) maintained on CNI served as controls. Secondary immunosuppressants were unchanged. Results. In the SRL group, GFR increased from 47.0±18.0 to 61.2±22.2 ml/min (P=0.0001) 24 months after SRL initiation. In Group A, GFR increased from 40.5±12.7 to 53.9±19.8 mL/min (P<0.0001). In Group B, GFR increased marginally from 67.2±15.8 to 83.5±27.8 mL/min (P=0.10). In the CNI group, GFR declined from 40.5±14.0 mL/min to 36.4±12.5 mL/min (P=0.23) after 24 months of follow up. There was no significant difference in cardiac rejection or cardiac allograft function. In SRL group, proteinuria increased from 299±622 mg/day to 517±795 mg/day (P=0.0002) 12 months after SRL initiation and then stabilized; it did not differ from CNI group at 24 months (637±806 vs. 514±744 mg/day, P=0.39). Uric acid decreased from 7.6±2.4 to 6.2±1.9 mg/dL (P=0.0007) in the SRL group. Conclusions. Graduated substitution of CNI with SRL in cardiac transplant recipients is safe and improves renal function, without cardiac compromise.

Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration

Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de and recellularization of large animal and human lungs including techniques which allow multiple small segments (∼ 1-3 cm(3)) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold.

Reoperative minimal access aortic valve surgery: Minimal mediastinal dissection and minimal injury risk

OBJECTIVE Minimizing surgical access in reoperative cardiac surgery allows limitation of dissection, trauma, and manipulation of patent bypass grafts. We report an 11-year experience with reoperative minimal access aortic valve surgery through an upper hemisternotomy. METHODS From July 1996 to June 2007 at our institution, 146 patients underwent reoperative minimal access aortic valve surgery, 109 of whom had undergone previous coronary artery bypass grafting and 93 of whom had a patent left internal thoracic artery graft. In patients with a patent left internal thoracic artery graft, the graft remained undissected. Myocardial protection was achieved with hypothermia, cold cardioplegia, and systemic hyperkalemia. Early and late outcomes were analyzed. RESULTS Median age was 76 years, and 43 patients (29%) were 80 years or older. Nineteen patients(13%) underwent concomitant procedures, such as coronary artery bypass grafting, mitral valve repair, and ascending aortic replacement. Median cardiopulmonary bypass and aortic crossclamp times were 150 and 80 minutes, respectively. Four patients (2.8%) had conversion to full sternotomy. Operative mortality was 4.1% (6/146). The incidences of reoperation for bleeding and blood transfusion were 0.7% (1/146) and 83.6% (122/146), respectively. No patient had left internal thoracic artery or aortocoronary graft injury. Median stay was 8 days, and 56% (79/140) were discharged home. Five-year actuarial survival was 85%. CONCLUSION An upper hemisternotomy approach for reoperative aortic valve surgery is safe and feasible. This approach minimizes tissue dissection and trauma, thereby reducing the risk of injury to patent grafts and mediastinal organs.

Bridge-to-Decision Therapy With a Continuous-Flow External Ventricular Assist Device in Refractory Cardiogenic Shock of Various Causes

Background—Mortality for refractory cardiogenic shock remains high. In this patient cohort, there have been mixed results in mechanical circulatory support device use as a bridge-to-decision therapy. We evaluated a continuous-flow external ventricular assist device (VAD), CentriMag VAD (Thoratec Corp., Pleasanton, CA), in patients with various causes of refractory cardiogenic shock. Methods and Results—This is a retrospective review of adult patients who underwent surgical CentriMag VAD insertion as bridge-to-decision therapy. From January 2007 through June 2012, 143 patients received CentriMag VAD. The cause of refractory cardiogenic shock was failure of medical management in 71 patients, postcardiotomy shock in 37, graft failure post–heart transplantation in 22, and right ventricular failure post–implantable left VAD in 13. Mean age was 52±16 years, and 71% were in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 1. Among 158 device runs, device configuration was BiVAD in 67%, isolated right VAD in 26%, and isolated left VAD in 8%. Median duration of support was 14 days (interquartile range, 8–26). Survival was 69% at 30 days and 49% at 1 year. The next destination after the CentriMag VAD was myocardial recovery in 30%, device exchange to an implantable VAD in 15%, and heart transplantation in 18%. The failure of medical management and the graft failure post–heart transplantation groups had higher 30-day survival compared with the postcardiotomy shock group. Major bleeding events occurred in 33% and cerebrovascular accidents in 14%. There was no CentriMag pump failure or thrombosis. Conclusions—Bridge-to-decision therapy with CentriMag VAD is feasible in a variety of refractory cardiogenic shock settings. Patients with postcardiotomy shock have inferior survival.