Peter S. Yoo

Reversal of muscle insulin resistance by weight reduction in young, lean, insulin-resistant offspring of parents with type 2 diabetes

To examine the role of intramyocellular lipid (IMCL) accumulation as well as circulating cytokines, branched-chain amino acids and acylcarnitines in the pathogenesis of muscle insulin resistance in healthy, young, lean insulin-resistant offspring of parents with type 2 diabetes (IR offspring), we measured these factors in plasma and used 1H magnetic resonance spectroscopy to assess IMCL content and hyperinsulinemic-euglycemic clamps using [6,6-2H2] glucose to assess rates of insulin-stimulated peripheral glucose metabolism before and after weight reduction. Seven lean (body mass index < 25 kg/m2), young, sedentary IR offspring were studied before and after weight stabilization following a hypocaloric (1,200 Kcal) diet for ∼9 wks. This diet resulted in an average weight loss of 4.1 ± 0.6 kg (P < 0.0005), which was associated with an ∼30% reduction of IMCL from 1.1 ± 0.2% to 0.8 ± 0.1% (P = 0.045) and an ∼30% improvement in insulin-stimulated muscle glucose uptake [3.7 ± 0.3 vs. 4.8 ± 0.1 mg/(kg–min), P = 0.01]. This marked improvement in insulin-stimulated peripheral insulin responsiveness occurred independently of changes in plasma concentrations of TNF-α, IL-6, total adiponectin, C-reactive protein, acylcarnitines, and branched-chain amino acids. In conclusion, these data support the hypothesis that IMCL accumulation plays an important role in causing muscle insulin resistance in young, lean IR offspring, and that both are reversible with modest weight loss.

Effect of aging on muscle mitochondrial substrate utilization in humans

Significance Approximately 40% of Americans over the age of 65 suffer from impaired glucose tolerance or type 2 diabetes; however, the pathogenesis of aging-associated reductions in glucose metabolism is poorly understood. Aging is associated with muscle insulin resistance, increased intramyocellular fat content, and reductions in rates of muscle mitochondrial activity. To further examine the potential role of age-associated alterations in mitochondrial metabolism, we applied a novel method to assess muscle specific rates of mitochondrial glucose and fat oxidation and demonstrate that aging is also associated with a marked inability of mitochondria to switch from lipid to glucose oxidation on insulin stimulation, which may further contribute to dysregulated glucose and lipid metabolism in the elderly. Previous studies have implicated age-associated reductions in mitochondrial oxidative phosphorylation activity in skeletal muscle as a predisposing factor for intramyocellular lipid (IMCL) accumulation and muscle insulin resistance (IR) in the elderly. To further investigate potential alterations in muscle mitochondrial function associated with aging, we assessed basal and insulin-stimulated rates of muscle pyruvate dehydrogenase (VPDH) flux relative to citrate synthase flux (VCS) in healthy lean, elderly subjects and healthy young body mass index- and activity-matched subjects. VPDH/VCS flux was assessed from the 13C incorporation from of infused [1-13C] glucose into glutamate [4-13C] relative to alanine [3-13C] assessed by LC-tandem MS in muscle biopsies. Insulin-stimulated rates of muscle glucose uptake were reduced by 25% (P < 0.01) in the elderly subjects and were associated with ∼70% (P < 0.04) increase in IMCL, assessed by 1H magnetic resonance spectroscopy. Basal VPDH/VCS fluxes were similar between the groups (young: 0.20 ± 0.03; elderly: 0.14 ± 0.03) and increased approximately threefold in the young subjects following insulin stimulation. However, this increase was severely blunted in the elderly subjects (young: 0.55 ± 0.04; elderly: 0.18 ± 0.02, P = 0.0002) and was associated with an ∼40% (P = 0.004) reduction in insulin activation of Akt. These results provide new insights into acquired mitochondrial abnormalities associated with aging and demonstrate that age-associated reductions in muscle mitochondrial function and increased IMCL are associated with a marked inability of mitochondria to switch from lipid to glucose oxidation during insulin stimulation.

Retransplantation of the Liver: Review of Current Literature for Decision Making and Technical Considerations

Liver transplantation (LTx) is an established treatment modality for patients with end-stage liver disease, metabolic disorders, and patients with acute liver failure. When a graft fails after primary LTx, retransplantation of the liver (reLTx) is the only potential cure. ReLTx accounts for 7%-10% of all LTx in the United States. Early causes of graft failure for which reLTx may be indicated include primary graft nonfunction and vascular inflow thrombosis. ReLTx in such cases in the early postoperative period is usually straightforward as long as an appropriate secondary allograft is secured in a timely fashion. Late indications may include ischemic cholangiopathy, chronic rejection, and recurrence of the primary liver disease. ReLTx performed in the late period is often more complex and selection criteria are more stringent due to the persistent shortage of organs. The question of whether to retransplant patients with recurrent hepatitis C remains controversial, but these practices are likely to change as the epidemic progresses and new treatments evolve. We also present recent results with reLTx from Yale-New Haven Transplant Center and early results with the use of living donors for reLTx.

Biliary complications adversely affect patient and graft survival after liver retransplantation

Inferior outcomes are consistently observed for recipients of liver retransplantation (re‐LT) versus recipients of primary transplants. Few studies have examined the incidence and impact of biliary complications (BCs) on outcomes after re‐LT. The aim of this study was to compare patient and graft survival for re‐LT recipients with BCs (BC+) and re‐LT recipients without BCs (BC−). Additional aims were to determine the impact of biliary reconstruction on the incidence of BCs and to identify risk factors for BCs after re‐LT. A single‐center, retrospective analysis of all re‐LT recipients over a decade was performed. Univariate analyses were performed, and survival was compared with the log‐rank method. A multivariate Cox regression analysis was performed to determine independent predictors of death and graft failure. The BC rate was 20.9% (n = 23) for 110 re‐LT cases. The average follow‐up was 55 months. The survival rates for BC− recipients at 3 months and 1, 3, and 5 years were 95.3%, 91.7%, 85.4%, and 80.9%, respectively, whereas BC+ patients had survival rates of 64.3%, 49.7%, 34.8%, and 29.8%, respectively (P < 0.001, log‐rank). The graft survival rates at 3 months and 1, 3, and 5 years were 92.0%, 88.5%, 82.4%, and 78.0%, respectively, for the BC− group and 60.9%, 43.5%, 30.4%, and 26.1%, respectively, for the BC+ group (P < 0.001, log‐rank). BCs, a length of stay ≥ 12 days, and donor age were strongly associated with death and graft failure in a regression analysis, whereas retransplant indications other than chronic rejection and recurrent disease also affected graft failure. In conclusion, BCs significantly affected both patient and graft survival, with an increased risk of death and graft loss among BC+ recipients. Early recognition, appropriate interventions, and preventative measures for BCs are critical in the clinical management of re‐LT recipients. Liver Transpl 19:965–972, 2013.

Attrition from surgical residency training: perspectives from those who left.

BACKGROUND High rates of attrition from general surgery residency may threaten the surgical workforce. We sought to gain further insight regarding resident motivations for leaving general surgery residency. METHODS We conducted in-depth interviews to generate rich narrative data that explored individual experiences. An interdisciplinary team used the constant comparative method to analyze the data. RESULTS Four themes characterized experiences of our 19 interviewees who left their residency program. Participants (1) felt an informal contract was breached when clinical duties were prioritized over education, (2) characterized a culture in which there was no safe space to share personal and programmatic concerns, (3) expressed a scarcity of role models who demonstrated better work-life balance, and (4) reported negative interactions with authority resulting in a profound loss of commitment. CONCLUSIONS As general surgery graduate education continues to evolve, our findings may inform interventions and policies regarding programmatic changes to boost retention in surgical residency.

Segmental grafts in adult and pediatric liver transplantation: improving outcomes by minimizing vascular complications.

IMPORTANCE The use of technically variant segmental grafts are key in offering transplantation to increase organ availability. OBJECTIVE To describe the use of segmental allograft in the current era of donor scarcity, minimizing vascular complications using innovative surgical techniques. DESIGN, SETTING, AND PARTICIPANTS Retrospective study from August 2007 to August 2012 at a university hospital. A total of 218 consecutive liver transplant patients were reviewed, and 69 patients (31.6%; 38 males and 31 females; mean age, 22.5 years) received segmental grafts from living donors or split/reduced-size grafts from deceased donors. MAIN OUTCOMES AND MEASURES Graft type, vascular and biliary complications, and patient and graft survival. RESULTS Of 69 segmental transplants, 47 were living donor liver transplants: 13 grafts (27.7%) were right lobes, 22 (46.8%) were left lobes, and 12 (25.5%) were left lateral segments. Twenty-two patients received deceased donor segmental grafts; of these, 11 (50.0%) were extended right lobes, 9 (40.9%) were left lateral segments, 1 (4.5%) was a right lobe, and 1 (4.5%) was a left lobe. Arterial anastomoses were done using 8-0 monofilament sutures in an interrupted fashion for living donor graft recipients and for pediatric patients. Most patients received a prophylactic dose of low-molecular-weight heparin for a week and aspirin indefinitely. There was no incidence of hepatic artery or portal vein thrombosis. Two patients developed hepatic artery stenosis and were treated with balloon angioplasty by radiology. Graft and patient survivals were 96% and 98%, respectively. CONCLUSIONS AND RELEVANCE Use of segmental allografts is essential to offer timely transplantation and decrease waiting list mortality. Living donor liver transplants and segmental grafts from deceased donors are complementary. It is possible to have excellent outcomes combining a multidisciplinary team approach, technical expertise, routine use of anticoagulation, and strict patient and donor selection.

Donation after cardiac death in pediatric organ transplantation.

Purpose of reviewThe purpose of this review is to describe the history, current practice, and outcomes of the transplantation of organs donated after cardiac death (DCD) in children. Recent findingsThe rate of death on the waiting list is greater for children under 5 years of age than for any other age group. The organ shortage experienced by the general population awaiting transplantation is made more complex due to the need for size-appropriate organs for transplantation into small children. Pediatric DCD organ recovery has been proposed as a means of ameliorating this shortage. SummaryThe use of DCD organs has experienced resurgence in the past 15 years, and a growing body of literature supports their use in selected cases. Recent experience in pediatric transplantation using DCD heart, lung, liver, and kidney is reviewed.

AVAS Best Clinical Resident Award (Tied): fate of non-designated preliminary general surgery residents seeking a categorical residency position.

BACKGROUND As pyramidal programs in general surgery were eliminated in recent decades, nondesignated preliminary surgery (NDPS) positions were introduced to fill vacant positions. Graduating medical students can pursue NDPS positions with the goal of obtaining categorical positions in either general surgery residencies or other fields altogether. The fate of residents who complete 2 years as NDPS residents remains ill defined. METHODS From 1997 to 2007, data concerning NDPS residents were prospectively collected from 2 general surgery training programs. Trainees were followed by prospectively gathered data, Internet identification, and internal records of hospital privileging. RESULTS One hundred ten graduating medical students initiated postgraduate training as NDPS residents. Seventy-four (67%) were men, and 98 (89%) were international medical graduates. Among all 110 subjects, 95 (86%) were hired as postgraduate year 1 NDPS residents, and 15 (14%) were hired as postgraduate year 2 NDPS residents. Fifteen (14%) left postgraduate medical education. Fifty-two NDPS residents (47%) pursued nonsurgical specialties after their internships. Forty-three (39%) eventually matriculated as categorical general surgical residents. Of these, 20 (47%) became categorical residents in their initial training programs. Nearly all NDPS residents who proceed to categorical positions obtained board certification. CONCLUSIONS More than one third of NDPS residents successfully obtained categorical general surgery positions. Only a small fraction (14%) failed to continue in postgraduate medical education. NDPS positions allow most candidates successful career paths. The persistent rate of attrition among categorical surgical residents allows NDPS residents to join categorical training programs and become eligible for board certification in general surgery.

Trainees as Agents of Change in the Opioid Epidemic: Optimizing the Opioid Prescription Practices of Surgical Residents

OBJECTIVE Opioid abuse has become an epidemic in the United States, causing nearly 50,000 deaths a year. Postoperative pain is an unavoidable consequence of most surgery, and surgeons must balance the need for sufficient analgesia with the risks of overprescribing. Prescribing narcotics is often the responsibility of surgical residents, yet little is known about their opioid-prescribing habits, influences, and training experience. DESIGN Anonymous online survey that assessed the amounts of postoperative opioid prescribed by residents, including type of analgesia, dosage, and number of pills, for a series of common general surgery procedures. Additional questions investigated influences on opioid prescription, use of nonnarcotic analgesia, degree of engagement in patient education on opioids, and degree of training received on analgesia and opioid prescription. SETTING Accreditation Council for Graduate Medical Education accredited general surgery program at a university-based tertiary hospital. PARTICIPANTS Categorical and preliminary general surgery residents of all postgraduate years. RESULTS The percentage of residents prescribing opioids postprocedure ranged from 75.5% for incision and drainage to 100% for open hernia repair. Residents report prescribing 166.3 morphine milligram equivalents of opioid for a laparoscopic cholecystectomy, yet believe patients will only need an average of 113.9 morphine milligram equivalents. The most commonly reported influences on opioid-prescribing habits include attending preference (95.2%), concern for patient satisfaction (59.5%), and fear of potential opioid abuse (59.5%). Only 35.8% of residents routinely perform a narcotic risk assessment before prescribing and 6.2% instruct patients how to properly dispose of excess opioids. More than 90% of residents have not had formal training in best practices of pain management or opioid prescription. CONCLUSION AND RELEVANCE Surgical trainees are relying almost exclusively on opioids for postoperative analgesia, often in excessive amounts. Residents are heavily influenced by their superiors, but are not receiving formal opioid-prescribing education, pointing to a great need for increased resident education on postoperative pain and opioid management to help change prescribing habits.

Senior Surgical Resident Confidence in Performing Flexible Endoscopy: What Can We Do Differently?

INTRODUCTION The American Board of Surgery endoscopy requirements for general surgery training are evolving. In 2006, the Residency Review Committee in Surgery increased the total number of endoscopy cases required before completion of general surgery residency training. This requirement is set to change further, given the new Flexible Endoscopic Curriculum that would be a requirement for applicants graduating surgical training during or after the 2017 to 2018 academic year. Given these changes, our goal was to evaluate the confidence of senior surgical residents performing flexible endoscopy. METHODS A survey was developed and sent to general surgery residents nationally, querying them regarding demographics and program-specific characteristics; additionally they were asked to rate their confidence level in performing flexible upper endoscopy and colonoscopy on a Likert scale of 1 to 5. We then compared those residents who indicated confidence (Likert scale 4-5) to those who did not (Likert scale 1-3). For the purpose of this study, only senior (postgraduate year 4 and 5) general surgery residents were assessed. RESULTS We received 1176 responses from senior surgical residents: 56% of these were postgraduate year 5 residents, 65% male, 68% from University Programs, and 56% from programs associated with a Veterans Affairs Hospital; 33% were from programs in the Northeast, 29% in the South, 24% in the Midwest, and 14% in the West; 75% were going on to additional fellowship training after the completion of residency; 42% indicated that they would go into academic practice and 32% into private practice; 66.7% reported confidence performing upper endoscopy and 52.7% reported confidence performing colonoscopy. Male gender, overall operative volume, and graduating from a medium-sized program or program in the South were associated with increased confidence performing flexible endoscopy. CONCLUSIONS A large percentage of senior residents do not report confidence in performing flexible endoscopy. Although increasing the number of cases required for graduation has likely helped improve the training of residents in endoscopy, additional improvements in training are required. The Flexible Endoscopic Curriculum helps standardize the curriculum and demonstrate that the graduating resident has the fundamental knowledge and skills required in the performance of endoscopy. Simulation training and dedicated endoscopic rotations during the course of residency training could help improve endoscopy training and proficiency for future graduating residents.