David Mulligan | Yale University School of Medicine (original) (raw)

Papers by David Mulligan

The American Journal of Gastroenterology, Sep 1, 2000

ABSTRACT

Scientific Reports, May 10, 2023

Tumor recurrence affects up to 70% of early-stage hepatocellular carcinoma (HCC) patients, depend... more Tumor recurrence affects up to 70% of early-stage hepatocellular carcinoma (HCC) patients, depending on treatment option. Deep learning algorithms allow in-depth exploration of imaging data to discover imaging features that may be predictive of recurrence. This study explored the use of convolutional neural networks (CNN) to predict HCC recurrence in patients with early-stage HCC from pre-treatment magnetic resonance (MR) images. This retrospective study included 120 patients with early-stage HCC. Pre-treatment MR images were fed into a machine learning pipeline (VGG16 and XGBoost) to predict recurrence within six different time frames (range 1-6 years). Model performance was evaluated with the area under the receiver operating characteristic curves (AUC-ROC). After prediction, the model's clinical relevance was evaluated using Kaplan-Meier analysis with recurrence-free survival (RFS) as the endpoint. Of 120 patients, 44 had disease recurrence after therapy. Six different models performed with AUC values between 0.71 to 0.85. In Kaplan-Meier analysis, five of six models obtained statistical significance when predicting RFS (log-rank p < 0.05). Our proof-of-concept study indicates that deep learning algorithms can be utilized to predict early-stage HCC recurrence. Successful identification of high-risk recurrence candidates may help optimize follow-up imaging and improve long-term outcomes post-treatment. Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death worldwide 1,2. Although early-stage HCC patients are treated with curative intent, the recurrence rates remain high. Recurrence risk has been noted to be as high as 70% for patients treated with surgical resection 3 or thermal ablation 4 and about 20% with orthotopic liver transplantation (OLT) 5 within 5 years post-treatment. Although patients with recurrence may undergo image-guided locoregional therapy or adjuvant systemic treatment with targeted agents such as sorafenib, supporting evidence for these approaches is limited 6-8. The diagnosis and staging of HCC are mainly based on cross-sectional body imaging, such as magnetic resonance (MR) imaging and computer tomography (CT). The size and number of tumors are the main criteria forming the foundation of various staging systems, for instance, the Barcelona Clinic Liver Cancer (BCLC) system 9. But, the lesion number and size do not adequately characterize the tumor biology or its characteristic imaging appearance. Thus, these systems cannot accurately estimate the patient's post-treatment recurrence risk.

Gastroenterology, May 1, 2023

Annals of Surgery, Jul 31, 2023

Objective: We evaluated long-term oncologic outcomes of patients post-LDLT within and outside sta... more Objective: We evaluated long-term oncologic outcomes of patients post-LDLT within and outside standard transplant selection criteria and the added value of the incorporation of the New York-California (NYCA) score. Summary Background Data: LDLT offers an opportunity to decrease the liver transplant waitlist, reduce waitlist mortality and expand selection criteria for patients with HCC. Methods: Primary adult LDLT recipients between Oct-1999 and Aug-2019 were identified from a multicenter cohort of twelve North American centers. Post-transplant and recurrence-free survival were evaluated using the Kaplan-Meier method. Results: Three-hundred-and-sixty LDLTs were identified. Patients within Milan criteria (MC) at transplant had a 1-,5-, and 10-year post-transplant survival of 90.9%,78.5%, and 64.1% vs. outside MC 90.4%,68.6%, and 57.7%(P=0.20). For patients within the UCSF criteria, respective post-transplant survival was 90.6%,77.8%, and 65.0%, vs. outside UCSF 92.1%,63.8%, and 45.8%(P=0.08). Fifty-three (83%) patients classified as outside MC at transplant would have been classified as either low- or acceptable risk with the NYCA score. These patients had a 5-year OS of 72.2%. Similarly, 28(80%) patients classified as outside UCSF at transplant would have been classified as low- or acceptable risk with a 5-year OS of 65.3%. Conclusions: Long-term survival is excellent for patients with HCC undergoing LDLT within and outside selection criteria, exceeding the minimum recommended 5-years rate of 60% proposed by consensus guidelines. The NYCA categorization offers insight into identifying a substantial proportion of patients with HCC outside the MC and the UCSF criteria who still achieve similar post-LDLT outcomes as patients within the criteria.

Clinical transplantation, Mar 16, 2023

John Wiley & Sons, Ltd eBooks, Aug 1, 2016

Transplantation Proceedings, Jun 1, 2011

Isolated failure of the renal graft after simultaneous kidney-pancreas transplantation (SPK) is a... more Isolated failure of the renal graft after simultaneous kidney-pancreas transplantation (SPK) is a rare but potential outcome. Many of these patients are candidates for kidney retransplantation. This paper describes a series of 3 patients who underwent successful kidney retransplantation after SPK. The operation was completed through an extraperitoneal incision without disruption of the pancreas graft or need for a transplant nephrectomy.

PubMed, 1993

An analysis of the first 740 liver transplants performed at Baylor is presented, including all ca... more An analysis of the first 740 liver transplants performed at Baylor is presented, including all cases to the end of calendar 1992. Kaplan-Meier curves are extended to nine years posttransplant. Our focus on outcome analysis has led us to review our experience with diabetics, with elderly patients, causes and patterns of late graft loss, long-term renal function. Quality of life data tracked for 2 years posttransplant is outlined. Clinical correlates to whole blood and plasma assays of FK506 are reviewed. Concerns remain over the disappointing results of liver transplantation for cholangiocarcinoma and those of patients with hepatitis-B antigenemia under current protocols.

Innovative Surgical Science, Jun 27, 2018

Vascular disease-including coronary artery disease, carotid artery disease, and peripheral vascul... more Vascular disease-including coronary artery disease, carotid artery disease, and peripheral vascular disease-is a leading cause of morbidity and mortality worldwide. The standard of care for restoring patency or bypassing occluded vessels involves using autologous grafts, typically the saphenous veins or internal mammary arteries. Yet, many patients who need life-or limbsaving procedures have poor outcomes, and a third of patients who need vascular intervention have multivessel disease and therefore lack appropriate vasculature to harvest autologous grafts from. Given the steady increase in the prevalence of vascular disease, there is great need for grafts with the biological and mechanical properties of native vessels that can be used as vascular conduits. In this review, we present an overview of methods that have been employed to generate suitable vascular conduits, focusing on the advances in tissue engineering methods and current three-dimensional (3D) bioprinting methods. Tissue-engineered vascular grafts have been fabricated using a variety of approaches such as using preexisting scaffolds and acellular organic compounds. We also give an extensive overview of the novel use of 3D bioprinting as means of generating new vascular conduits. Different strategies have been employed in bioprinting, and the use of cell-based inks to create de novo structures offers a promising solution to bridge the gap of paucity of optimal donor grafts. Lastly, we provide a glimpse of our work to create scaffold-free, bioreactorfree, 3D bioprinted vessels from a combination of rat vascular smooth muscle cells and fibroblasts that remain patent and retain the tensile and mechanical strength of native vessels.

Peritoneal Dialysis International, Nov 1, 1997

Peritonitis is considered an acceptable and controllable risk in patients undergoing chronic peri... more Peritonitis is considered an acceptable and controllable risk in patients undergoing chronic peritoneal dialysis (PD). In contrast, peritonitis due to visceralleakage represents a true "abdominal catastrophe" because of striking morbidity and mortality. To delineate the incidence, causes, and outcomes of catastrophic peritonitis, we compared patients who developed peritonitis due to documented visceral leakage with patients who developed peritonitis due to enteric organisms without evidence of visceral leakage. .Design: Retrospective chart review. .Setting: PD Unit located in tertiary care referral center. .Patients: 230 patients treated by PD between January 1988 and June 1996. .Main Outcome Measures: All episodes of PD-related peritonitis occurring over an 8-year period. Hospital course of all patients with or without renal failure who were treated at University Hospitals of Cleveland for ischemic bowel disease, cholecystitis, viscus perforation, or diverticulitis. .Results: Anatomically documented visceral injury caused 32.5% of episodes of enteric bacterial peritonitis in 72 patients between January 1988 and June 1996. The overall incidence of this "abdominal catastrophe" was 11.3%, or 26 of a total of 230 patients treated by PD. Of the 26 patients, 50% died, 30.7% survived but switched permanently to hemodialysis, and only 19.2% remained on, or returned to, PD. Compared to renal failure patients treated by hemodialysis or transplantation and to nonrenal failure patients, the incidence of abdominal catastrophe was 20-60 times greater in patients treated by PD. .Conclusions: Evidence for injury of an abdominal organ should be sought in allpatients treated by PD who develop peritonitis with enteric organisms. Surgical intervention is definitive for diagnosis, and if performed early may reduce morbidity and mortality.

This is an open access article distributed in accordance with the CC-BY-NC-ND (Creative Commons A... more This is an open access article distributed in accordance with the CC-BY-NC-ND (Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International) license. The article can be used by giving appropriate credit and mentioning the license, but only for noncommercial purposes and only in the original version.

Current Opinion in Organ Transplantation, Jun 1, 2004

ABSTRACT Purpose of review: Liver transplantation is widely accepted as the mainstay of treatment... more ABSTRACT Purpose of review: Liver transplantation is widely accepted as the mainstay of treatment for end-stage liver disease. Unfortunately, the waiting lists are outgrowing the supply of donor livers, forcing more aggressive practices to use marginal organs, non-heart beating donor livers, and partial liver grafts. Recent findings: Several clinical and experimental studies have examined new preservation solutions, such as histidine-tryptophan-ketoglutarate and Celsior, in addition to methods of continuous perfusion that appear promising. Clinical studies have shown that new preservation solutions can have outcomes after liver transplantation that are effective and less costly than the conventional University of Wisconsin solution. In experimental models, the identification of pathways leading to ischemia and reperfusion injury and the manipulation of these mediators may lead to clinical studies in the future. Summary: This review summarizes recent and novel advances in the application of organ preservation solutions and techniques to liver transplantation.

Liver Transplantation, Mar 28, 2016

In June of 2013, the Organ Procurement and Transplantation Network (OPTN) implemented regional sh... more In June of 2013, the Organ Procurement and Transplantation Network (OPTN) implemented regional sharing for Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) candidates with scores reaching 35 and above ("Share 35"). The goal of this distribution change was to increase access to lifesaving transplants for the sickest candidates with chronic liver disease and to reduce the waiting-list mortality for this medically urgent group of patients. To assess the impact of this change, we compared results before and after policy implementation at 2 years. Overall, there were more liver transplants performed under Share 35 and a greater percentage of MELD/PELD 351 candidates underwent transplantation; waiting-list mortality rates in this group were also significantly lower in the post-policy period. Overall adjusted waiting-list mortality was decreased slightly, with no significant changes in mortality by age group or ethnicity. Posttransplant graft and patient survival was unchanged overall and was unchanged for the MELD/PELD 351 recipients. In conclusion, these data demonstrate that the Share 35 policy achieved its goal of increasing access to transplants for these medically urgent patients without reducing access to liver transplants for pediatric and minority candidates. Although the variance in the median MELD at transplant as well as the variance in transport distance increased, there was a decrease in overall liver discard rates and no change in overall cold ischemia times following broader sharing of these organs. The OPTN will continue to monitor this policy, particularly for longer-term posttransplant survival outcomes.

Transplantation, Jun 1, 2002

Bacterial infection is a frequent, morbid, and mortal complication of liver transplantation. Sele... more Bacterial infection is a frequent, morbid, and mortal complication of liver transplantation. Selective bowel decontamination (SBD) has been reported to reduce the rate of bacterial infection after liver transplantation in uncontrolled trials, but benefits of this intervention have been less clear in controlled studies. Eighty candidates for liver transplantation were randomly assigned in a double-blinded fashion to an SBD regimen consisting of gentamicin 80 mg+polymyxin E 100 mg+nystatin 2 million units (37 patients) or to nystatin alone (43 patients). Both treatments were administered orally in 10 ml (increasing to 20 ml, according to predefined criteria), four times daily, through day 21 after transplantation. Anal fecal swab cultures were performed on days 0, 4, 7, and 21. Rates of infection, death, and charges for medical care were assessed from day 0 through day 60. More than 85% of patients in both treatment groups began study treatment more than 3 days before transplantation. Rates of infection (32.4 vs. 27.9%), death (5.4 vs. 4.7%), or charges for medical care (median 194,000vs.194,000 vs. 194,000vs.163,000) were not reduced in patients assigned to SBD. On days 0, 4, 7, and 21, growth of aerobic gram-negative flora in fecal cultures of patients assigned to SBD was significantly less than that of patients taking nystatin alone; growth of aerobic gram-positive flora, anaerobes, and yeast was not significantly different. Routine use of SBD in patients undergoing liver transplantation is not associated with significant benefit.

Liver Transplantation, 2004

The new allocation policy of the United Network of Organ Sharing (UNOS) based on the model for en... more The new allocation policy of the United Network of Organ Sharing (UNOS) based on the model for end-stage liver disease (MELD) gives candidates with stage T1 or stage T2 hepatocellular carcinoma (HCC) a priority MELD score beyond their degree of hepatic decompensation. The aim of this study was to determine the impact of the new allocation policy on HCC candidates before and after the institution of MELD. The UNOS database was reviewed for all HCC candidates listed between July 1999 and July 2002. The candidates were grouped by two time periods, based on the date of implementation of new allocation policy of February 27, 2002. Pre-MELD candidates were listed for deceased donor liver transplantation (DDLT) before February 27,2002, and post-MELD candidates were listed after February 27, 2002. Candidates were compared by incidence of DDLT, time to DDLT, and dropout rate from the waiting list because of clinical deterioration or death, and survival while waiting and after DDLT. Incidence rates calculated for pre-MELD and post-MELD periods were expressed in person years. During the study, 2,074 HCC candidates were listed for DDLT in the UNOS database. The DDLT incidence rate was 0.439 transplant/person years pre-MELD and 1.454 transplant/person years post-MELD (P < 0.001). The time to DDLT was 2.28 years pre-MELD and 0.69 years post-MELD (P < 0.001). The 5-month dropout rate was 16.5% pre-MELD and 8.5% post-MELD (P < 0.001). The 5-month waiting-list survival was 90.3% pre-MELD and 95.7% post-MELD (P < 0.001). The 5-month survival after DDLT was similar for both time periods. The new allocation policy has led to an increased incidence rate of DDLT in HCC candidates. Furthermore, the 5-month dropout rate has decreased significantly.

Transplant Infectious Disease, Sep 21, 2022

Background: Surgical site infections (SSIs) are common complications after surgeries, usually lea... more Background: Surgical site infections (SSIs) are common complications after surgeries, usually leading to increased health care costs. Therefore, we evaluated the efficiency of current preoperative antibiotic prophylaxis and risk factors of SSIs in the orthopedic wards in a major teaching hospital in China. Methods: We retrospectively reviewed a population of 2,061 patients who underwent orthopedic surgeries between January 2010 and January 2012 and examined the bacterial isolates and their resistance patterns associated with orthopedic infections. Moreover, a multivariate logistic regression was used to identify independent risk factors for SSIs. Results: Thirty-three out of the 45 clinical SSIs were culture positive, and a total of 35 bacterial strains was isolated, among which, 65.72% (n ¼ 23) were gram-positive isolates, and 34.28% (n ¼ 12) were gramnegative bacteria. Significantly, 68.6% of all bacterial isolates were resistant to cefuroxime. Additionally, this study found that diabetes mellitus (odds ratio [OR], 7.539), smoking (OR, 2.378), duration of surgeries longer than 3 hours (OR, 3.633), absence of antibiotic prophylaxis (OR, 6.562), and previous operations (OR, 2.190) were crucial independent risk factors associated with a significant increase in the development rate of SSIs following orthopedic incisional operations. Conclusion: Our data suggested that appropriate modifications to antibiotic prophylaxis regimens should be considered. Furthermore, tightening glucose control, stopping smoking, providing proper antibiotic prophylaxis, and shortening surgery time are promising approaches to reduce the SSIs rate.

PubMed, Dec 1, 1995

In this report we demonstrate that the use of immunoabsorbent beads to remove the OKT3 monoclonal... more In this report we demonstrate that the use of immunoabsorbent beads to remove the OKT3 monoclonal antibody (MoAb) from the sera of transplant recipients is necessary in order to avoid the false positive reactivity in panel reactive antibody (PRA) assay. We have shown that the presence of OKT3 MoAb in patient's sera can give a positive reactivity in PRA, which may be interpreted as antibody development. Rabbit antimouse immunoglobulin covalently linked to sepharose can effectively remove the OKT3 MoAb from patients sera, but has no effect on anti-HLA antibodies. The absorbance of OKT3 MoAb, therefore, is necessary to obtain accurate results in respect to humoral rejection, which may lead to mismanagement of patients.

InTech eBooks, May 2, 2018

The need for liver transplant and its timely nature are both equally vital for a patient with end... more The need for liver transplant and its timely nature are both equally vital for a patient with end stage liver disease. But the ever-growing need for liver transplant across the entire world threatens the two reasons that justify its very existence. The popularity of living donor liver transplant has met great enthusiasm amongst the transplant physicians and surgeons, as it is timely, and also yields superior survival benefit as compared to a deceased donor liver transplant. Living donor liver transplant has been constantly adapting to meet the needs of patients and the expanding wait list. The need for a living donor liver transplant is not the same amongst the various parts of the world, because the population and the disease burden is different. We looked at the trend of living donor liver transplant across the world and also the change in practices over time including a glimpse of what lies ahead for the next decades.