The impact of statins on biological characteristics of stem cells provides a novel explanation for their pleiotropic beneficial and adverse clinical effects.

Statins reduce atherosclerotic events and cardiovascular mortality. Their side effects include memory loss, myopathy, cataract formation, and increased risk of diabetes. As cardiovascular mortality relates to plaque instability, which depends on the integrity of the fibrous cap, we hypothesize that the inhibition of the potential of mesenchymal stem cells (MSCs) to differentiate into macrophages would help to explain the long known, but less understood "non-lipid-associated" or pleiotropic benefit of statins on cardiovascular mortality. In the present investigation, MSCs were treated with atorvastatin or pravastatin at clinically relevant concentrations and their proliferation, differentiation potential, and gene expression profile were assessed. Both types of statins reduced the overall growth rate of MSCs. Especially, statins reduced the potential of MSCs to differentiate into macrophages while they exhibited no direct effect on macrophage function. These findings suggest that the limited capacity of MSCs to differentiate into macrophages could possibly result in decreased macrophage density within the arterial plaque, reduced inflammation, and subsequently enhance plaque stability. This would explain the non-lipid-associated reduction in cardiovascular events. On a negative side, statins impaired the osteogenic and chondrogenic differentiation potential of MSCs and increased cell senescence and apoptosis, as indicated by upregulation of p16, p53 and Caspase 3, 8, and 9. Statins also impaired the expression of DNA repair genes, including XRCC4, XRCC6, and Apex1. While the effect on macrophage differentiation explains the beneficial side of statins, their impact on other biologic properties of stem cells provides a novel explanation for their adverse clinical effects.

The impact of surgical volume on racial disparity in thyroid and parathyroid surgery.

PURPOSE: The aim of this study was to evaluate the association between surgeon volume and patient outcomes among different race ethnicities undergoing thyroid or parathyroid surgery. METHODS: The nationwide inpatient sample was used to identify all thyroidectomy and parathyroidectomy admissions from 2003 to 2009, using International Classification of Diseases, 9th Clinical Modification (ICD-9-CM) procedure codes. Race, demographic, and clinical characteristics of patients were collected, along with surgeon volume, to predict the length of stay (LOS), complication rates, mortality, and total charges by racial group, using univariate and multivariate analyses. RESULTS: A total of 106,314 thyroid and parathyroid surgeries were included in the current analysis. Of these patients, 54 % were Caucasian, 11 % African American, 7 % Hispanic, and 3 % Asian. Mean LOS was longer for African American patients (4 ± 8.7 days) than for Caucasians (2.3 ± 5.5 days) [p < 0.001]. African Americans had higher overall complications (16.8 %) compared with Caucasians (11 %), Hispanics (13.5 %), and Asians (12 %) [p < 0.001]. In-hospital mortality was higher for African Americans (0.8 %) compared with that from other race groups (0.3 %) [p < 0.001]. Mean total charges were significantly higher for African Americans ($33,292 ± $67,387) compared with those for Caucasians ($22,855 ± $40,167) (p < 0.001). African Americans had less access to intermediate- (10-99 cases) and high- (>100 cases) volume surgeons compared with Caucasians-45 versus 49 %, and 16 versus 19 %, respectively (p < 0.001). Higher surgeon volume was associated with improved outcomes (p < 0.001). Racial disparity in all investigated outcomes was still significantly evident even after stratification by surgeon volume. CONCLUSION: Higher surgeon volume is associated with improved patient outcomes. However, our data suggests that the observed racial disparities in thyroid and parathyroid surgery go beyond access to quality healthcare providers.

Using simulation to improve root cause analysis of adverse surgical outcomes.

OBJECTIVE: The purpose of this study was to develop and test a simulation method of conducting investigation of the causality of adverse surgical outcomes. DESIGN: Six hundred and thirty-one closed claims of a major medical malpractice insurance company were reviewed. Each case had undergone conventional root cause analysis (RCA). Claims were categorized by comparing the predominant underlying cause documented in the case files. Three cases were selected for simulation. SETTING: All records (medical and legal) were analyzed. Simulation scenarios were developed by abstracting data from the records and then developing paper and electronic medical records, choosing appropriate STUDY PARTICIPANTS: including test subjects and confederates, scripting the simulation and choosing the appropriate simulated environment. INTERVENTION: In a simulation center, each case simulation was run 6-7 times and recorded, with participants debriefed at the conclusion. MAIN OUTCOME MEASURES: Sources of error identified during simulation were compared with those noted in the closed claims. Test subject decision-making was assessed qualitatively. RESULTS: Simulation of adverse outcomes (SAOs) identified more system errors and revealed the way complex decisions were made by test subjects. Compared with conventional RCA, SAO identified root causes less focused on errors by individuals and more on systems-based error. CONCLUSIONS: The use of simulation for investigation of adverse surgical outcomes is feasible and identifies causes that may be more amenable to effective systems changes than conventional RCA. The information that SAO provides may facilitate the implementation of corrective measures, decreasing the risk of recurrence and improving patient safety.

Complications of liver resection: laparoscopic versus open procedures.

BACKGROUND AND OBJECTIVE: Minimally invasive surgery for liver resection remains controversial. This study was designed to compare open versus laparoscopic surgical approaches to liver resection. METHODS: We performed a single-center retrospective chart review. RESULTS: We compared 45 laparoscopic liver resections with 17 open cases having equivalent resections based on anatomy and diagnosis. The overall complication rate was 25.8%. More open resection patients had complications (52.9% vs 15.5%, P < .008). The conversion rate was 11.1%. The mean blood loss was 667.1 ± 1450 mL in open cases versus 47.8 ± 89 mL in laparoscopic cases (P < .0001). Measures of intravenous narcotic use, intensive care unit length of stay, and hospital length of stay all favored the laparoscopic group. Patients were more likely to have complications or morbidity in the open resection group than in the laparoscopic group for both the anterolateral (P < .085) and posterosuperior (P < .002) resection subgroups. CONCLUSION: In this series comparing laparoscopic and open liver resections, there were fewer complications, more rapid recovery, and lower morbidity in the laparoscopic group, even for those resections involving the posterosuperior segments of the liver.

Disability and kidney transplantation in the United States.

Transplantation is the treatment of choice for patients with end-stage renal disease. Despite complete or partial restoration of renal function, many recipients after transplant continue to self-identify as disabled. It is a designation required for federal healthcare assistance pre-transplant, but in some cases, post-transplantation, the designation is misapplied. When kidney recipients bear the label of disabled, regardless if the disability is real or perceived, they are less likely to participate in work and social activities. Although transplantation improves quality of life, for many recipients the designation of disability can extend an unintended, negative impact. It is well recognized that kidney recipients return to employment, education, and social activities after transplantation. However, there is a portion of the recipient population that can work but chooses not to engage. A large part of the phenomenon is related to disability status and the federal financing of kidney disease. This paper summarizes the history of the relationship between disability and kidney transplantation, the potential pitfalls associated with the relationship, and evidence-based strategies designed to mitigate or lead to mitigation of the unfavorable effects associated with misappropriated, perceived disability after kidney transplantation.

Using Process Flow Disruption Analysis to Guide Quality Improvement.

BACKGROUND: Process flow describes the efficiency and consistency with which a process functions. Disruptions in surgical flow have been shown to be associated with an increase in error. Despite this, little experience exists in using surgical flow analysis to guide quality improvement (QI). STUDY DESIGN: In a 900-bed teaching hospital with an annual surgical volume of 24,000 cases, a 4-month observational study of process flow was done by experts in complex system evaluation. Identified flow disruptions were used to guide QI. Statistical analysis included descriptive and bivariate techniques. RESULTS: More than 200 unique process data points were evaluated. There was a high degree of variability in completion of 79 individual intraoperative data elements. Lack of completion of all elements of the time out was associated with number of times the operating room door opened during case (19, 11-27; p = 0.01). Flow disruptions were used to direct surgical QI. One example was a disruption affecting the use of Sugammadex. Resolving this flow disruption resulted in a 59% reduction in the incidence of postoperative respiratory failure (p < 0.01) and a direct and variable cost savings of $447,200 and $313,160, respectively, in the first 12 months. CONCLUSIONS: The use of process flow analysis to direct surgical quality initiatives is a novel approach that emphasizes system-level strategy. Resolving flow disruptions can lead to effective QI that embraces reliability by focusing attention on common processes rather than adverse events that may be unique and therefore difficult to apply broadly.

P-selectin expression in cold preserved kidneys in University of Wisconsin and histidine-tryptophan-ketoglutarate solutions.

The differences and efficacy of standard preservation solutions in kidney transplantation, University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK), remain a topic of debate in recent clinical studies. P-selectins represent glycoproteins expressed on endothelial cells and platelets responsible for the earliest events in ischemia/reperfusion injury in kidney transplantation. This study aimed to compare the levels of P-selectin expression between cold preserved kidney tissues in UW and HTK solutions. Thirty kidneys were procured from male Lewis rats and stored in cold (4°C) solutions for periods of 4, 12, 16, 20, and 24h. Group 1 (n=15) kidneys were stored in UW solutions, and group 2 (n=15) kidneys were submerged in HTK solutions. At the end of each time point, the kidneys underwent preparation and levels of P-selectin expression in the tissues were measured using Immunoblot analyses and adjusted volumetric quantification of Western blot signals. For all periods of cold preservation, P-selectin expression was significantly down-regulated in kidney tissues stored in UW compared with HTK solutions (P<0.001). In summary, UW demonstrated a significant benefit over HTK solution in down-regulating P-selectin expression in cold preserved kidney grafts.

Who's your donor? Bringing about Louisiana's first domino paired exchange transplants.

Although living donation is the preferred method of kidney transplant, many donors are not a match with their intended recipient. One unique way of overcoming this is by performing a donor paired exchange. By swapping donors, transplant centers may be able to bring about multiple transplants that would not have otherwise been possible. This manuscript describes the first three way domino paired donor exchange transplant in Louisiana. Because of a single altruistic donor, we were able to facilitate three recipients getting transplanted. We discuss the formulation of this unique program, the choosing of potential donor/recipient pairs and outcomes. A review of the controversies of paired kidney donation is also presented.

Applying international organization for standards 9001 to create an effective surgical quality committee.

BACKGROUND: Efforts to improve surgical safety are limited by several factors and no consensus exists regarding the most effective way to improve surgical quality. The use of ISO 9001 quality standards within healthcare is recognized but has not been widely applied for improving surgical outcomes. METHODS: A surgical quality committee was created using ISO 9001:2015 standards. Quality objectives were assessed to understand how any suggested changes will be impacted due to risks and opportunities inherent in the system. RESULTS: The initial quality focus was on surgical site infections in 5 services. Change in surgical infection ratio from 2018 to 2019 showed significant improvement: coronary bypass 1.288 vs. 0.901; Colon 1.359 vs. 0.589; Hysterectomy 2.119 vs. 1.022; Knee 1.391 vs. 0.306; Hip 0 vs. 0.302. CONCLUSIONS: This is one of the first studies using ISO 9001 to improve surgical quality. The results indicate both acceptance and success of applying continual improvement strategies.

Characterization of hematopoietic potential of mesenchymal stem cells.

Mesenchymal and hematopoietic tissues are important reservoirs of adult stem cells. The potential of tissue resident mesenchymal stem cells (MSCs) to differentiate into cells of mesodermal and ectodermal lineages has been reported previously. We examined the hypothesis that adherent adipose tissue resident mesenchymal stem cells (ASCs) are capable of generating cells with hematopoietic characteristics. When cultured in differentiation media, clonally isolated ASCs develop into cells with hematopoietic attributes. The hematopoietic differentiated cells (HD) express early hematopoietic (c-kit, PROM1, CD4) as well as monocyte/macrophage markers (CCR5, CD68, MRC1, CD11b, CSF1R). Additionally, HD cells display functional characteristics of monocyte/macrophages such as phagocytosis and enzymatic activity of α-Naphthyl Acetate Esterase. HD cells are also responsive to stimulation by IL-4 and LPS as shown by increased CD14 and HLA-DRB1 expressions and release of IL-2, IL10, and TNF. Taken together, this study characterizes the potential of ASCs to generate functional macrophages in vitro, and therefore paves way for their possible use in cell therapy applications.

The effect of HLA mismatch on highly sensitized renal allograft recipients.

INTRODUCTION: We examined the effects of increasing human leukocyte antigen (HLA) mismatches (MM) on long-term graft outcomes in patients transplanted with a panel reactive antibody (PRA) >80% over a 10-yr period. METHODS: A total of 142 recipients were divided into three groups based on the number of HLA MM with their allograft (0-2, 3-4 and 5-6 MM; Groups I, II and III). All patients received the same immunosuppression protocol. RESULTS: The higher MM groups had a higher incidence of rejection (4.4% vs. 11.4% vs. 31.3%, p < 0.01). A multivariate analysis showed that rejection was the only significant variable affecting graft loss (OR = 7.45, p = 0.01). There was a trend toward more CMV infection and worse graft function with higher MM. Kaplan-Meier five-yr graft survival estimates were 100% vs. 81% vs. 74% for Groups I, II and III, respectively (p = 0.14). CONCLUSIONS: In patients with PRA levels >80%, a higher HLA MM is associated with higher incidence of acute rejection. Acute rejection was the only significant variable affecting graft loss. We found a trend toward more CMV infections and worse graft outcomes with higher MM. Closer HLA matching and immunologic monitoring needs to be considered to improve graft outcomes among sensitized recipients.

Management of monophasic synovial sarcoma of the small intestine.

BACKGROUND: Reports of primary intraabdominal synovial sarcomas are extremely rare. METHODS: A literature review using PubMed was performed. A retrospective review of the one known case at our institution was completed. RESULTS: Even the most experienced pathologists report that synovial sarcomas can be very difficult to diagnose correctly. One cytogenic abnormality that is common (> 90%) and pathognomonic for synovial sarcoma is a characteristic chromosomal translocation resulting in the SYT/SSX fusion gene. Wide regional excision has been performed for intraabdominal sarcoma, with improved results. Our patient is more than 24 months with no evidence of recurrent or metastatic disease. CONCLUSIONS: The prognosis for patients with intraabdominal synovial sarcoma remains poor. However, wide regional excision may allow for prolonged disease-free survival.

ECMO During Combined Heart-Kidney Transplantation: A Case Report.

Combined heart-kidney transplantation (CHKT) is a therapy for a carefully selected subgroup of patients with concomitant heart and kidney failure. Discerning whether there is reversible or irreversible kidney disease is crucial to selection for CHKT versus heart transplant alone to optimize therapeutic value and organ allocation. Methods for determining extent of kidney disease include estimating glomerular filtration rate, creatinine clearance, kidney ultrasonography, and kidney biopsy. Additionally, the use of extracorporeal membrane oxygenation (ECMO) in the setting of CHKT only recently emerged as feasible. We present a case of a 69-year-old man with cardiogenic shock who was placed on venoarterial-ECMO (VA-ECMO) following orthotopic heart transplant (OHT) due to severe mediastinal bleeding and remained on VA-ECMO during kidney transplant. To our knowledge, this is the second report of a patient undergoing kidney transplant while on VA-ECMO following OHT.

Laparoscopic management of massive hemobilia from an intrahepatic aneurysm.

BACKGROUND: Intrahepatic arterial aneurysms are rare and typically related to trauma, transplantation, iatrogenic injury, or infection. They account for approximately 10% of clinically significant hemobilia. CASE REPORT: We present the case of a 49-year-old man with an intraparenchymal hepatic artery aneurysm that presented as massive hemobilia following a laparoscopic cholecystectomy. The aneurysm could not be managed by interventional embolization and required a left hepatic lobectomy, which was performed laparoscopically. DISCUSSION: Evaluation of hemobilia requires a multidisciplinary team approach. The diagnosis of hepatic artery aneurysm can be most readily made by MRI or CT scan. Interventional embolization of the aneurysm may be effective treatment but is not always possible due to anatomic considerations. Where indicated, surgical resection in a manner that preserves a maximal amount of normal hepatic parenchyma is the treatment of choice. CONCLUSION: This is the first report of laparoscopic liver resection performed for bleeding from a hepatic artery aneurysm and adds an effective treatment modality to the surgical armamentarium.

Interstitial pneumonitis in the transplant patient: consider sirolimus-associated pulmonary toxicity.

Interstitial pneumonia in a transplant patient can have a varied etiology. Sirolimus (Rapamycin; Rapamune) is a popularly used immunosuppressant in solid organ transplantation that has anecdotally been associated with pulmonary toxicity. Sirolimus-induced pulmonary toxicity consists of a range of syndromes that is characterized by the presence of organizing pneumonia, interstitial pneumonitis, pulmonary alveolar proteinosis, focal fibrosis, or by the presence of alveolar hemorrhage. Diagnosis can be challenging and is usually made by exclusion of other etiologies. In this report we present two cases of sirolimus-associated pulmonary toxicity with a review of the literature.

Dermal matrix as a carrier for in vivo delivery of human adipose-derived stem cells.

The aim of the present study was to evaluate the potential of acellular dermal matrix as a carrier for delivery of stem cells to the site of soft tissue defect in a murine skin injury model and to determine the potential of stem cells delivered via such an approach to successfully engraft, survive and differentiate locally. We showed that adipose-derived stem cells delivered via this matrix survived after in vivo engraftment, spontaneously differentiated along vascular endothelial, fibroblastic and epidermal epithelial lineages and significantly improved wound healing. Furthermore, an organ survey for transplanted cells showed no evidence of a systemic distribution beyond the cutaneous wound site, indicating that the adipose-derived stem cell-dermal matrix construct provides a novel and effective method for anatomically focused cellular therapy. In conclusion, stem cell-seeded dermal matrix is an effective means for targeted in vivo cell delivery for enhanced soft tissue regeneration.

The Change in Surgical Case Diversity Over the Past 15 Years and the Influence on the Pursuit of Surgical Fellowship.

The surgical community has expressed concern that residents do not receive the same caliber training as their predecessors and the increase in fellowships have been described as secondary to perceived lack of preparation. Yet, data show no change in total cases even after implementation of the 80-hour workweek. It is hypothesized that the increasing subspecialization of general surgery may decrease in certain resident case numbers. Data were collected from the Accreditation Council for Graduate Medical Education (ACGME) General Surgery Case Logs National Data Report (1999-2014) of mean number of procedures per resident for 19 surgical categories. Statistical analysis was performed with analysis of variance over three time periods between 1999 and 2014. The number of total cases performed by residents has not changed significantly. There was a statistically significant difference observed in the variety of cases: vascular, esophageal, breast, and trauma cases decreased (P < 0.01), whereas major intestinal, hernia, liver, pancreatic, and biliary cases increased (P < 0.01). There are many reasons to pursue additional training after residency. The demonstrated change in case variability, presumably secondary to increasing fellowships, may play a significant role on training and preparation. Close monitoring of curriculums is essential to ensure a comprehensive general surgical education.

Factors leading to pancreatic resection in patients with pancreatic cancer: a national perspective.

BACKGROUND: Resection is the only option for potential cure in pancreatic cancer. Patients admitted for resection may have the procedure deferred during their hospitalization. We aim to identify factors that lead pancreatic cancer patients to undergo resection. METHODS: An analysis utilizing the Nationwide Inpatient Sample (NIS) database, 2003-2009. Study population included adults (≥18 years) with pancreatic cancer who underwent either pancreatic resection or other interventions. Surgeon volume classified based on the median into low and high-volume surgeon. RESULTS: Eleven thousand three hundred and sixty-five patients were included; 68.0% underwent pancreatic resection, while 32.0% had other interventions. The majority of patients resected were <60 years old, female, with higher annual household income (P<0.05 for all). Patients with Medicaid coverage and comorbidity scores ≥2 were least likely to undergo pancreatic resection. Resection was more likely for high-volume surgeons, high-volume hospitals and teaching hospitals (P<0.05 for all). Those managed by high-volume surgeons were at a lower risk of postoperative complications, lower mortality, shorter hospital stay, and lower healthcare costs (P<0.05 for all). CONCLUSIONS: Patients' insurance type and economic status are significantly associated with their ability to achieve pancreatic resection. Surgeon experience and hospital volumes were also significantly associated with pancreatic resection, clinical and economic outcomes.

Living donor kidney transplantation: medical, legal, and ethical considerations.

The use of living donor kidneys has dramatically increased the number and success of kidney transplants across the world. But questions remain regarding the subjection of a healthy individual to surgery for the benefit of another. Donors do have medical and financial risks. The stigma of organ brokering remains today, with evidence of commercial transplantation in other countries. Here in the US, we are exposed to advertising for donors using the media. In the hope of increasing living donations, we run the risk of stretching altruism too far. In this manuscript, we highlight and discuss some of the current controversies surrounding living donor kidney transplantation across the world.

Choosing Surgery: Identifying Factors Leading to Increased General Surgery Matriculation Rate.

Tulane graduates have, over the past six years, chosen general surgical residency at a rate above the national average (mean 9.6% vs 6.6%). With much of the recent career choice research focusing on disincentives and declining general surgery applicants, we sought to identify factors that positively influenced our students' decision to pursue general surgery. A 50-question survey was developed and distributed to graduates who matched into a general surgery between the years 2006 and 2014. The survey evaluated demographics, exposure to surgery, and factors affecting interest in a surgical career. We achieved a 54 per cent (61/112) response rate. Only 43 per cent considered a surgical career before medical school matriculation. Fifty-nine per cent had strongly considered a career other than surgery. Sixty-two per cent chose to pursue surgery during or immediately after their surgery clerkship. The most important factors cited for choosing general surgery were perceived career enjoyment of residents and faculty, resident/faculty relationship, and mentorship. Surgery residents and faculty were viewed as role models by 72 and 77 per cent of responders, respectively. This study demonstrated almost half of those choosing a surgical career did so as a direct result of the core rotation experience. We believe that structuring the medical student education experience to optimize the interaction of students, residents, and faculty produces a positive environment encouraging students to choose a general surgery career.