Does utilization of heart machine perfusion for donation after cardiac death transplantation affect outcomes of other abdominal transplanted organs?

INTRODUCTION: Machine perfusion of heart for donation after circulatory death (DCD) is being increasingly utilized. Current protocols for utilizing heart DCD's machine perfusion might prolong donor warm ischemic time for nonheart organs. The aim of this study was to analyze the effects of utilizing heart machine perfusion on liver and kidney transplants from the same donor. METHODS: We analyzed data of DCD donors from the United Network for Organ Sharing (UNOS) from January-2020 to September-2021 among two groups: donors with heart machine perfusion (HM) and without heart machine perfusion (NHM). Propensity score (PS) matching was performed to compare the short-term outcomes of liver and kidney transplants between two groups. RESULTS: Total of 102 liver and 319 kidney transplants were performed using organs from donors with HM. After PS matching, no statistically significant difference was seen in 1-year graft survival (GS) for both liver and kidney transplants between two groups (liver HM 90.6% vs. NHM 90.2%, p = .47; kidney HM 95.2% vs. NHM 92.9%, p = .40). There was no difference in the delayed graft function (DGF) rates in kidney transplantation (KT) (HM 42% vs. NHM 35%, p = .062). CONCLUSION: Utilization of heart machine perfusion in DCD donors had no significant impact on 1-year outcomes of liver and kidney transplantation.

Successful liver transplantation in a patient recovered from COVID-19.

Transplantation in potential candidates who have recently recovered from COVID-19 is a challenge with uncertainties regarding the diagnosis, multi-organ systemic involvement, prolonged viral shedding in immunocompromised patients, and optimal immunosuppression. A 42 year male with alcoholic hepatitis underwent a successful deceased donor liver transplantation 71 days after the initial diagnosis of COVID-19. At the time of transplant, he was SARS-CoV-2 PCR negative for 24 days and had a MELD score of 33. His post-operative course was complicated by acute rejection which responded to intense immune-suppression using T-cell depletion and steroids. He was discharged with normal end-organ function and no evidence of any active infection including COVID-19. Prospective organ transplant recipients who have recovered from COVID-19 can be considered for transplantation after careful pre-transplant evaluation, donor selection, and individualized risk-benefit analysis.

Implementation of the High-Risk Alcoholism Relapse Scale in a Liver Transplant Clinic.

Because of the high prevalence of alcohol relapse after liver transplantation, transplant programs are challenged to evaluate alcoholism among liver transplant patients. Relapse after liver transplantation can have detrimental outcomes such as organ rejection, medical and social resource exhaustion, financial burden to the family and society, and negative public perception of organ transplantation. The purpose of this project was to improve post-liver transplant assessment for the risk of relapse to heavy alcohol use by implementing a protocol using the High-Risk Alcoholism Relapse (HRAR) scale (DiMartini et al., 2000; Yates et al., 1993). The project was conducted in an urban organ transplant center's outpatient post liver transplant clinic. Chart reviews assessed the process of patients identified as being at high risk and the transplant providers' completion of the HRAR scale. Eleven percent of patients assessed were identified as being at high risk for relapse of heavy alcohol use and 85% of providers used the HRAR scale in their clinic interviews. This project demonstrates that further refinements in techniques of predicting the risks of relapse are necessary, and nurses are in ideal positions to screen patients for alcohol use.

BK Polyomavirus microRNA in Kidney Transplant Recipient.

BK polyomavirus-associated nephropathy (PyVAN) remains a serious threat for renal dysfunction and graft loss in kidney transplant recipients on immunosuppressive medication. In this study, a pilot cohort of 16 kidney transplant recipients were recruited of which eight were with significant BKPV viremia (sBKPV) and the rest were controls matched to age, gender, and time since transplant. We used next-generation sequencing to characterize the miRNA expression profile in urine samples. In total, the expression of 8 miRNAs (miR-16-5p,miR-200c-3p,bkv-miR-B1-3p,let-7b-3p,miR-1269b,bkv-miR-B1-5p,miR-193a-3p,miR-944) were upregulated whereas 21miRNAs (miR-134-5p,miR-4724-5p,miR-127-3p,miR-6500-3p,miR-507,miR-378b,miR-3911,miR-211-5p,miR-486-5p,miR-143-3p,miR-3195,miR-1307-5p,miR-29a-5p,miR-378f,miR-12136,miR-378g,miR-144-3p,miR-378a-3p,let-7i-5p,miR-204-5p,miR-146a-5p) were downregulated with fold change > 2. We found that bkv-miR-B1-5p and bkv-miR-B1-3p have 19-fold and 5-fold higher expression values in BKPV viremia patient samples, respectively. A few earlier studies have reported BKV miRNA in urine and serum samples using the RT- PCR from PyVAN patients. Our results corroborated findings from earlier studies and highlighted the need for additional evaluation of the role of sequencing approaches for monitoring BKPV specific and host miRNAs to better understand the viral reactivation and disease pathogenesis.

Inferior outcomes of liver transplantation for hepatocellular carcinoma during early-COVID-19 pandemic in the United States.

BACKGROUND: Early in the coronavirus disease 2019 (COVID-19) pandemic, there was a significant impact on routine medical care in the United States, including in fields of transplantation and oncology. AIM: To analyze the impact and outcomes of early COVID-19 pandemic on liver transplantation (LT) for hepatocellular carcinoma (HCC) in the United States. METHODS: WHO declared COVID-19 as a pandemic on March 11, 2020. We retrospectively analyzed data from the United Network for Organ Sharing (UNOS) database regarding adult LT with confirmed HCC on explant in 2019 and 2020. We defined pre-COVID period from March 11 to September 11, 2019, and early-COVID period as from March 11 to September 11, 2020. RESULTS: Overall, 23.5% fewer LT for HCC were performed during the COVID period (518 vs 675, P < 0.05). This decrease was most pronounced in the months of March-April 2020 with a rebound in numbers seen from May-July 2020. Among LT recipients for HCC, concurrent diagnosis of non-alcoholic steatohepatitis significantly increased (23 vs 16%) and alcoholic liver disease (ALD) significantly decreased (18 vs 22%) during the COVID period. Recipient age, gender, BMI, and MELD score were statistically similar between two groups, while waiting list time decreased during the COVID period (279 days vs 300 days, P = 0.041). Among pathological characteristics of HCC, vascular invasion was more prominent during COVID period (P < 0.01), while other features were the same. While the donor age and other characteristics remained same, the distance between donor and recipient hospitals was significantly increased (P < 0.01) and donor risk index was significantly higher (1.68 vs 1.59, P < 0.01) during COVID period. Among outcomes, 90-day overall and graft survival were the same, but 180-day overall and graft were significantly inferior during COVID period (94.7 vs 97.0%, P = 0.048). On multivariable Cox-hazard regression analysis, COVID period emerged as a significant risk factor of post-transplant mortality (Hazard ratio 1.85; 95%CI: 1.28-2.68, P = 0.001). CONCLUSION: During COVID period, there was a significant decrease in LTs performed for HCC. While early postoperative outcomes of LT for HCC were same, the overall and graft survival of LTs for HCC after 180 days were significantly inferior.

Is Compensation Prediction Score Valid for Contralateral Kidney After Living-Donor Nephrectomy in the United States?

BACKGROUND: Compensation after living donor nephrectomy is well known, and a compensation prediction score (CPS) was made in Japan previously. The aim of this study was to perform external validation of CPS in the United States. METHODS: We studied retrospectively 78 living donor nephrectomies in our institution. We defined a favorable compensation as a postdonation estimated glomerular filtration rate (eGFR) at 1 year of >60% of the predonation eGFR. We analyzed the living donors' clinical characteristics and outcomes and validated CPS score. RESULTS: The median (range) donor age was 43 (21-63) years, and median body mass index was 26.9 (18.3-35.9) kg/m2. Forty-four percent of donors were White. The donor predonation eGFR was 105 (61-134) mL/min/1.73 m2, and the postdonation eGFR at 1 year was 73.2 (0-115) mL/min/1.73 m2. Eighty-three percent of donors had a favorable compensation. The CPS was 9.6 (1.6-15.6) and showed strong diagnostic accuracy for predicting favorable compensation (area under the curve, 0.788; 95% confidence interval, 0.652-0.924; P = .001). The CPS showed a significant positive correlation with the postdonation eGFR at 1 year (R = 0.54; P < .001). CONCLUSIONS: In the United States, the CPS would be a valid tool with which to predict a favorable compensation of remnant kidney function.

Improving Liver Transplant Outcomes for Hepatitis C Virus Hepatocellular Carcinoma in the Direct-Acting Antiviral Therapy Era.

BACKGROUND: Direct-acting antiviral (DAA) therapy has transformed the outcomes of liver transplant (LT) with hepatitis C virus (HCV). This study aimed to analyze the effects of DAA treatment for HCV-associated hepatocellular carcinoma (HCC) in LT. METHODS: We included patients confirmed with HCC on explant, analyzed data from United Network for Organ Sharing, and defined the pre-DAA era (2012-2013) and DAA era (2014-2016). RESULTS: HCV-associated HCC cases totaled 4778 (62%) during the study period. In the DAA era, the median recipient age was older and the median days on the waiting list were longer. For the donor, median age, body mass index, and the rate of HCV significantly increased in the DAA era. In pathology, the median largest tumor size was significantly higher; however, the rate of completed tumor necrosis was significant higher in the DAA era. The 3-year graft/patient survival had significantly improved in the DAA era. In multivariable analysis, the DAA era (hazard ratio, 0.79; 95% confidence interval, 0.68-0.91) had significantly affected the 3-year graft survival. CONCLUSIONS: DAA has a significant beneficial effect on LT. In the DAA era, graft survival for HCV-associated HCC has been significantly improving.

Trends and outcomes of liver transplantation among older recipients in the United States.

BACKGROUND: The average age of recipients and donors of liver transplantation (LT) is increasing. Although there has been a change in the indications for LT over the years, data regarding the trends and outcomes of LT in the older population is limited. AIM: To assess the clinical characteristics, age-related trends, and outcomes of LT among the older population in the United States. METHODS: We analyzed data from the United Network for Organ Sharing database between 1987-2019. The sample was split into younger group (18-64 years old) and older group (≥ 65 years old). RESULTS: Between 1987-2019, 155758 LT were performed in the United States. During this period there was a rise in median age of the recipients and percentage of LT recipients who were older than 65 years increased (P < 0.05) with the highest incidence of LT among older population seen in 2019 (1920, 23%). Common primary etiologies of liver disease leading to LT in older patients when compared to the younger group, were non-alcoholic steatohepatitis (16.4% vs 5.9%), hepatocellular carcinoma (14.9% vs 6.9%), acute liver failure (2.5% vs 5.2%), hepatitis C cirrhosis (HCV) (19.2 % vs 25.6%) and acute alcoholic hepatitis (0.13% vs 0.35%). In older recipient group female sex and Asian race were higher, while model for end-stage liver disease (MELD) score and rates of preoperative mechanical ventilation were lower (P < 0.01). Median age of donor, female sex, body mass index (BMI), donor HCV positive status, and donor risk index (DRI) were significantly higher in older group (P < 0.01). In univariable analysis, there was no difference in post-transplant length of hospitalization, one-year, three-year and five-year graft survivals between the two groups. In multivariable Cox-Hazard regression analysis, older group had an increased risk of graft failure during the five-year post-transplant period (hazard ratio: 1.27, P < 0.001). Other risk factors for graft failure among recipients were male sex, African American race, re-transplantation, presence of diabetes, mechanical ventilation at the time of LT, higher MELD score, presence of portal vein thrombosis, HCV positive status, and higher DRI. CONCLUSION: While there is a higher risk of graft failure in older recipient population, age alone should not be a contraindication for LT. Careful selection of donors and recipients along with optimal management of risk factors during the postoperative period are necessary to maximize the transplant outcomes in this population.

Quantitative evaluation of acute renal transplant dysfunction with low-dose three-dimensional MR renography.

PURPOSE: To assess prospectively the ability of quantitative low-dose three-dimensional magnetic resonance (MR) renography to help identify the cause of acute graft dysfunction. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board, and written informed consent was obtained. Between December 2001 and May 2009, sixty patients with transplanted kidneys (41 men and 19 women; mean age, 49 years; age range, 22-71 years) were included. Thirty-one patients had normal function and 29 had acute dysfunction due to acute rejection (n = 12), acute tubular necrosis (ATN) (n = 8), chronic rejection (n = 6), or drug toxicity (n = 3). MR renography was performed at 1.5 T with three-dimensional gradient-echo imaging. With use of a multicompartment renal model, the glomerular filtration rate (GFR) and the mean transit time (MTT) of the tracer for the vascular compartment (MTT(A)), the tubular compartment (MTT(T)), and the collecting system compartment (MTT(C)) were calculated. Also derived was MTT for the whole kidney (MTT(K) = MTT(A) + MTT(T) + MTT(C)) and fractional MTT of each compartment (MTT(A/K) = MTT(A)/MTT(K), MTT(T/K) = MTT(T)/MTT(K), MTT(C/K) = MTT(C)/MTT(K)). These parameters were compared in patients in the different study groups. Statistical analysis was performed by using analysis of covariance. RESULTS: There were significant differences in GFR and MTT(K) between the acute dysfunction group (36.4 mL/min ± 20.8 [standard deviation] and 177.1 seconds ± 46.8, respectively) and the normal function group (65.9 mL/min ± 27.6 and 140.5 seconds ± 51.8, respectively) (P < .001 and P = .004). The MTT(A/K) was significantly higher in the acute rejection group (mean, 12.7% ± 2.9) than in the normal function group (mean, 8.3% ± 2.2; P < .001) or in the ATN group (mean, 7.1% ± 1.4; P < .001). The MTT(T/K) was significantly higher in the ATN group (mean, 83.2% ± 9.2) than in the normal function group (mean, 72.4% ± 10.2; P = .031) or in the acute rejection group (mean, 69.2% ± 6.1; P = .003). CONCLUSION: Low-dose MR renography analyzed by using a multicompartmental tracer kinetic renal model may help to differentiate noninvasively between acute rejection and ATN after kidney transplantation.

Successful Management of COVID-19 Infection in 2 Early Post-Liver Transplant Recipients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has affected all facets of life and continues to cripple nations. COVID-19 has taken the lives of more than 2.1 million people worldwide, with a global mortality rate of 2.2%. Current COVID-19 treatment options include supportive respiratory care, parenteral corticosteroids, and remdesivir. Although COVID-19 is associated with increased risk of morbidity and mortality in patients with comorbidities, the vulnerability, clinical course, optimal management, and prognosis of COVID-19 infection in patients with organ transplants has not been well described in the literature. The treatment of COVID-19 differs based on the organ(s) transplanted. Preliminary data suggested that liver transplant patients with COVID-19 did not have higher mortality rates than untransplanted COVID-19 patients. Table 1 depicts a compiled list of current published data on COVID-19 liver transplant patients. Most of these studies included both recent and old liver transplant patients. No distinction was made for early liver transplant patients who contract COVID-19 within their posttransplant hospitalization course. This potential differentiation needs to be further explored. Here, we report 2 patients who underwent liver transplantation who acquired COVID-19 during their posttransplant recovery period in the hospital. CASE DESCRIPTIONS: Two patients who underwent liver transplant and contracted COVID-19 in the early posttransplant period and were treated with hydroxychloroquine, methylprednisolone, tocilizumab, and convalescent plasma. This article includes a description of their hospital course, including treatment and recovery. CONCLUSION: The management of post-liver transplant patients with COVID-19 infection is complicated. Strict exposure precaution practice after organ transplantation is highly recommended. Widespread vaccination will help with prevention, but there will continue to be patients who contract COVID-19. Therefore, continued research into appropriate treatments is still relevant and critical. A temporary dose reduction of immunosuppression and continued administration of low-dose methylprednisolone, remdesivir, monoclonal antibodies, and convalescent plasma might be helpful in the management and recovery of severe COVID-19 pneumonia in post-liver transplant patients. Future studies and experiences from posttransplant patients are warranted to better delineate the clinical features and optimal management of COVID-19 infection in liver transplant recipients.

"You've got mail!": the role of e-mail in clinical breast surgical practice.

Easy Internet access is changing the practice of medicine in the US. At least 137 million Americans have access to the World Wide Web, and up to one-half would like to communicate with their physicians by e-mail. The membership of the American Society of Breast Surgeons was surveyed to evaluate the current role of e-mail in patient-doctor relationships. Due to the extensive discussions often involved in the evaluation of breast disease, and the elective nature of most surgical procedures, this specialty may be particularly well-suited to using e-mail communication as an extension of discussions during traditional office visits. A questionnaire was e-mailed to all members of the ASBS who had provided an e-mail address. About 1236 questionnaires were sent, and 285 surgeons responded, a 23% response rate. About 130 (46%) responders were female; 209 responders (73%) did not use e-mail to communicate with patients (76% of responding females, 70% of males). The oldest and youngest surgeons were least likely to use e-mail to communicate with patients. There was no gender-related difference in e-mail use. There was no difference in e-mail use between surgeons who limit their practice to breast disease and those who do not. Urban and university-based surgeons were more likely to use e-mail. Medical-legal liability concerns and confidentiality issues were the most common reasons for not using e-mail. Among those surgeons who did use e-mail, ability to answer at one's own discretion, and the ability to provide an organized response were the major reasons for using e-mail. Overall, the membership expressed a preference for personal interaction over electronic communication.

Intramammary lymph nodes and breast cancer: a marker for disease severity, or just another lymph node?

BACKGROUND: Axillary lymph node status is still considered the most significant prognostic factor for breast cancer outcome, and treatment decisions are based on the presence or absence of nodal disease. Intramammary lymph nodes (IMLNs) can be a site of regional spread. Is this a marker for more aggressive disease? METHODS: We reviewed the cancer center pathology database from 1991 to 2005 for all cases of breast cancer with IMLNs. RESULTS: IMLNs were identified in 64 breast cancer patients, with metastatic spread in 20 patients, and benign IMLNs described in 44 patients. Positive IMLNs were associated with more aggressive disease, including higher rates of invasive versus noninvasive cancers (5% ductal carcinoma-in-situ [DCIS] with positive IMLNs vs. 23% with negative IMLNs), lymphovascular invasion (55% vs. 11%), and a higher rate of axillary lymph node involvement (72% vs. 18%). Patients with positive IMLNs were also more likely to undergo mastectomy (75% vs. 54%). CONCLUSIONS: IMLN metastases are a marker for disease severity; recognition of this may influence choice of adjuvant therapy. The presence of metastatic disease in an IMLN is associated with a high rate of axillary nodal involvement, and should mandate axillary dissection. Preoperative lymphoscintigraphy may help identify these extra-axillary metastases.

A pilot study of letrozole for one year in women at enhanced risk of developing breast cancer: effects on mammographic density.

BACKGROUND: Tamoxifen or raloxifen for 5 years reduces the risk of developing invasive breast cancer by 40%. To address safety concerns and seek enhanced efficacy, studies of new chemopreventive agents using mammographic density as a surrogate end point are attractive. PATIENTS AND METHODS: Postmenopausal women with risk factors for developing breast cancer were given letrozole 2.5 mg daily for one year, and mammographic density was the biomarker of breast cancer risk modification. It was assessed (blinded to the reader) at baseline, 6, and 12 months in 16 evaluable women among 20 enrolled. RESULTS: Eight patients exhibited decreased mammographic density at six months, and eleven at 12 months. Toxicities included joint aches not precluding continued treatment. CONCLUSION: This pilot study supports the use of letrozole for reducing breast cancer risk. In addition, it encourages prospective studies of serial changes in mammographic density as a biomarker of risk modification within a selected high-risk population.

A decade of change: an institutional experience with breast surgery in 1995 and 2005.

INTRODUCTION: With the adoption of routine screening mammography, breast cancers are being diagnosed at earlier stages, with DCIS now accouting for 22.5% of all newly diagnosed breast cancers. This has been attributed to both increased breast cancer awareness and improvements in breast imaging techniques. How have these changes, including the increased use of image-guided sampling techniques, influenced the clinical practice of breast surgery? METHODS: The institutional pathology database was queried for all breast surgeries, including breast reconstruction, performed in 1995 and 2005. Cosmetic procedures were excluded. The results were analysed utilizing the Chi-square test. RESULTS: Surgical indications changed during 10-year study period, with an increase in preoperatively diagnosed cancers undergoing definitive surgical management. ADH, and to a lesser extent, ALH, became indications for surgical excision. Fewer surgical biopsies were performed for indeterminate abnormalities on breast imaging, due to the introduction of stereotactic large core biopsy. While the rate of benign breast biopsies remained constant, there was a higher percentage of precancerous and DCIS cases in 2005. The overall rate of mastectomy decreased from 36.8% in 1995 to 14.5% in 2005. With the increase in sentinel node procedures, the rate of ALND dropped from 18.3% to 13.7%. Accompanying the increased recognition of early-stage cancers, the rate of positive ALND also decreased, from 43.3% to 25.0%. CONCLUSIONS: While the rate of benign breast biopsies has remained constant over a recent 10-year period, fewer diagnostic surgical image-guided biopsies were performed in 2005. A greater percentage of patients with breast cancer or preinvasive disease have these diagnoses determined before surgery. More preinvasive and Stage 0 cancers are undergoing surgical management. Earlier stage invasive cancers are being detected, reflected by the lower incidence of axillary nodal metastases.

Intrahepatic portal cavernoma as an indication for liver transplantation.

Cavernous transformation of the portal vein (portal cavernoma) consists of a periportal or/and intrahepatic venous collateral network, developed as a result of acute or long-standing portal vein thrombosis. Better control of hemorrhagic and thrombotic complications in the patients with portal cavernoma substantially improves their life span and the clinical outcome. However, biliary complications that occur in the late stages of this disease have been recently recognized as challenging management issues because they recur and are difficult to treat. Because of the relatively small number of the patients with cholangiopathy due to portal cavernoma, there is no current standardized treatment approach. We report the case of a predominantly intrahepatic portal cavernoma occurring in a patient with chronic idiopathic portal vein thrombosis, which led to severe cholangiopathy that mimicked primary sclerosing cholangitis and cholangiocarcinoma, was unresponsive to endoscopic stent placement, and finally required liver transplantation.

Public health lessons learned from analysis of New York City subway injuries.

Serious subway injuries are devastating to their young victims and have high rates of mortality and amputation. We identified the urban population at greatest risk for subway injuries and investigated the influence of local economies on injury rates. We propose using changes in social conditions as a "trigger" for increased vigilance and protective measures at times of higher risk.