Genetics of aortic valve disease.

PURPOSE OF REVIEW: Aortic valve disease is a leading global cause of morbidity and mortality, posing an increasing burden on society. Advances in next-generation technologies and disease models over the last decade have further delineated the genetic and molecular factors that might be exploited in development of therapeutics for affected patients. This review describes several advances in the molecular and genetic understanding of AVD, focusing on bicuspid aortic valve (BAV) and calcific aortic valve disease (CAVD). RECENT FINDINGS: Genomic studies have identified a myriad of genes implicated in the development of BAV, including NOTCH1 , SMAD6 and ADAMTS19 , along with members of the GATA and ROBO gene families. Similarly, several genes associated with the initiation and progression of CAVD, including NOTCH1 , LPA , PALMD , IL6 and FADS1/2 , serve as the launching point for emerging clinical trials. SUMMARY: These new insights into the genetic contributors of AVD have offered new avenues for translational disease investigation, bridging molecular discoveries to emergent pharmacotherapeutic options. Future studies aimed at uncovering new genetic associations and further defining implicated molecular pathways are fuelling the new wave of drug discovery.

No Gains in Long-term Survival After Liver Transplantation Over the Past Three Decades.

OBJECTIVE: The aim of this study was to assess improvements in long-term survival after liver transplant by analyzing outcomes in transplant recipients who survived beyond 1 year. SUMMARY OF BACKGROUND DATA: Gains in short-term survival following liver transplantation have been gratifying. One-year survival in 1986 was 66% improved to over 92% in 2015. However, little is known about why long-term has not seen similar success. METHODS: We analyzed 111,568 recipients from 1987 to 2016 using the Kaplan-Meier method for time-to-event analysis and multivariable Cox regression. RESULTS: There were no significant gains in unadjusted long-term outcomes among 1-year survivors over the past 30 years. Only the time periods of 1987 to 1990 [hazard ratio (HR) 1.35, confidence interval CI) 1.28-1.42] and 1991 to 1995 (HR 1.17, CI 1.13-1.21) had a minor increase in risk compared with the period 2011 to 2016. Cause of death analysis suggests malignancy after transplantation is a growing problem and preventing recurrent hepatitis C with direct-acting antivirals (DDAs) may only have a limited impact. Furthermore, rejection leading to graft failure and death had a rare occurrence (1.7% of long-term deaths) especially when compared with the sequelae of long-term immunosuppression: malignancy (16.4%), nonrejection graft failure (9.8%), and infection (10.5%) (P < 0.001). CONCLUSION: In stark contrast to short-term survival, there have been no appreciable improvements in long-term survival following liver transplantation among 1-year survivors. Long-term sequelae of immunosuppression, including malignancy and infection, are the most common causes of death. This study highlights the need for better long-term immunosuppression management.

Intraoperative blood loss and transfusion during primary pediatric liver transplantation: A single-center experience.

Children undergoing liver transplantation are at a significant risk for intraoperative hemorrhage and thrombotic complications, we aim to identify novel risk factors for massive intraoperative blood loss and transfusion in PLT recipients and describe its impact on graft survival and hospital LOS. We reviewed all primary PLTs performed at our institution between September 2007 and September 2016. Data are presented as n (%) or median (interquartile range). EBL was standardized by weight. Massive EBL and MT were defined as greater than the 85th percentile of the cohort. 250 transplantations were performed during the study period. 38 (15%) recipients had massive EBL, and LOS was 31.5 (15-58) days compared to 11 (7-21) days among those without massive EBL (P < 0.001). MT median LOS was 34 (14-59) days compared to 11 (7-21) days among those without MT (P = 0.001). Upon backward stepwise regression, technical variant graft, operative time, and transfusion of FFP, platelet, and/or cryoprecipitate were significant independent risk factors for massive EBL and MT, while admission from home was a protective factor. Recipient weight was a significant independent risk factor for MT alone. Massive EBL and MT were not statistically significant for overall graft survival. MT was, however, a significant risk factor for 30-day graft loss. PLT recipients with massive EBL or MT had significantly longer LOS and increased 30-day graft loss in patients who required MT. We identified longer operative time and technical variant graft were significant independent risk factors for massive EBL and MT, while being admitted from home was a protective factor.

Preventable operating room delays in robotic-assisted thoracic surgery: Identifying opportunities for cost reduction.

BACKGROUND: This study aimed to characterize the types of intraoperative delays during robotic-assisted thoracic surgery, operating room staff awareness/perceptions of delays, and cost impact of delays on overall operative costs. METHODS: Robotic-assisted thoracic surgery cases from May to August 2019 were attended by 3 third-party observers to record intraoperative delays. The postoperative surveys were given to operating room staff to elicit perceived delays. Observed versus perceived delays were compared using the McNemar test. Direct costs and charges per delay were calculated. RESULTS: Forty-four cases were observed, of which a majority were lobectomies (n = 38 [86%]). A total of 71 delays were recorded by observers, encompassing 75% of cases (n = 33), with an average delay length of 3.6 minutes (±5.3 minutes). The following delays were observed: equipment failure (n = 40, average delay length 5.0 minutes (±6.5 minutes), equipment missing (n = 15, 2.2 minutes [±1.4 minutes]), staff unfamiliarity with equipment (n = 4, 3.4 minutes [± 1.5 minutes]), and other (n = 12, 4.5 minutes [±5.3 minutes]). The detection rates for any intraoperative delay were consistently lower for all of the operating room team members compared with observers, including surgeons (34.3% vs 77.1%; P = .0003), first assistants (41.9% vs 74.2%; P = .0075), surgical technologists (39.4% vs 72.7%; P = .0045), and circulating nurses (41.18% vs 76.47% minutes; P = .0013). The average operating room variable direct cost of delays based on the average total delay length per case was $225.52 (±$350.18) and was 1.6% (range 0-10.6%) of the total case charges. CONCLUSION: The lack of perception of intraoperative delays hinders operating teams from effectively closing the variable cost gaps. Future studies are needed to explore methods of increasing perception of delays and opportunities to improve operating room efficiency.

Cancer Care in the Incarcerated Population: Barriers to Quality Care and Opportunities for Improvement.

Importance: Cancer is the leading cause of mortality in incarcerated individuals older than 45 years and the fourth leading cause of mortality overall. Health care professionals face increasing challenges to provide high-quality care under the confines of prison regulations and procedures. Observations: Adjusted for age, race, sex, and year of diagnosis, the standardized incidence ratio for all cancers is more than 2-fold higher in incarcerated vs general populations. Among deaths occurring in state and federal prison systems, cancer is the overall leading cause of mortality with lung cancer being the leading cause of cancer-related mortality followed by liver, colon, and pancreatic cancers, respectively. Access to high-quality oncological services remains variable; however, cost of care represents about a fifth of overall annual prison expenditures. Given the enormous patient burden, coupled with the rushed discretionary screenings performed by jail and prison nursing staff, early cancer symptoms are often missed altogether or misdiagnosed as a chronic illness or as acute infections. As such, many incarcerated individuals present with more advanced cancer stage. Incarcerated individuals have limited, if any, access to the internet, social media, and other sources of information, which severely limits their ability to research treatment options. Within the prison setting, access to professionals with special skills in assisting with social and spiritual concerns is also generally limited, and less than 4% of prisons have hospice programs. There are no uniform quality-of-care monitoring standards for correctional systems and facilities, nor are there mechanisms for reporting comparable performance data to enforce quality control within correctional health care systems. Conclusions and Relevance: There is a growing trend in cancer incidence among incarcerated patients, which is multifactorial including barriers in access to care, increased burden of chronic medical conditions, and decreased screening tests. Efforts are needed to ensure quality health care outcomes for incarcerated patients with cancer.

Is Organ Retransplantation Among Undocumented Immigrants in the United States Just?

Numerous undocumented children in the United States with end-stage renal disease undergo kidney transplantation funded by charitable donation or state-sponsored Medicaid. However, when these funding sources expire by adulthood, most are unable to pay for follow-up appointments and immunosuppressive medications necessary for maintenance of their organ. The organs fail and patients are then left with the options of retransplantation or a lifetime of dialysis. The dilemma of retransplantation introduces many questions regarding justice and fairness. This commentary addresses several ethical concerns about the special case of organ retransplantation for undocumented patients. Clinical guidelines and a clear public policy for best practices are needed to adequately address the challenge of retransplantation and maintenance immunosuppression in this population.

Reoperative complications following pediatric liver transplantation.

BACKGROUND: The aim of this study is to describe the incidence and impact of reoperation following pediatric liver transplantation, as well as the indications and risk factors for these complications. METHODS: All primary pediatric liver transplants performed at our institution between January 2012 and September 2016 were reviewed. A reoperative complication was defined as a complication requiring return to the operating room within 30 days or the same hospital admission as the transplant operation, excluding retransplantation. RESULTS: Among the 144 pediatric liver transplants performed during the study period, 9% of the recipients required reoperation. The most common indications for reoperation were bleeding and bowel complications. There was no significant difference in the graft survival of patients with a reoperation and those without a reoperation (p = 0.780), but patients with a reoperation had a significantly longer hospital length of stay (median of 39 days vs. 11 days, p = 0.001). Variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate were significantly associated with reoperation upon univariable logistic regression, but none of these risk factors remained statistically significant upon multivariable regression. CONCLUSION: At our institution, reoperation did not significantly impact graft survival. We identified variant donor arterial anatomy, transplant operative time, intraoperative blood loss, transfusion volume of packed red blood cells or cell saver per weight, and transfusion with fresh frozen plasma, platelets, or cryoprecipitate as risk factors for reoperation, although none of these risk factors demonstrated independent association with reoperation in a multivariable model. TYPE OF STUDY: Prognosis Study. LEVEL OF EVIDENCE: Level III.