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Objective In the era of organ shortage, redo liver transplantation (reLT) is frequently discussed in terms of expected poor outcome, high cost and therefore wasteful resources. However, there is a lack of benchmark data to reliably assess outcomes after reLT. The aim of this study was to define the ideal reLT case, and to establish clinically relevant benchmark values for best achievable outcome in reLT. Methods We collected data on reLT between January 2010 and December 2018 from 22 high volume transplant centers on three continents. Benchmark cases were defined as recipients with model of end-stage liver disease score Results Out of 1110 reLT 413 (37.2%) qualified as benchmark cases. Benchmark values included: Length of intensive care unit and hospital stay: =3a complications and the CCI at 1 year: Conclusion ReLT remains associated with high morbidity and mortality. The availability of benchmark values for outcome parameters of reLT may serve for comparison in any future analyses of individuals, patient groups, or centers, but also in the evaluation of new therapeutic strategies and principles.

Patients with cirrhosis have increased risk of postoperative mortality. Several models have been developed to estimate this risk; however, current risk estimation scores cannot compare surgical risk with the risk of not operating.To identify clinical optimal thresholds to favor operative or nonoperative management for a common cirrhosis surgical scenario, the symptomatic abdominal hernia.This was a Markov cohort decision analytical modeling study evaluating elective surgery vs nonoperative management for a symptomatic abdominal hernia in a patient with cirrhosis. Transition probabilities and utilities were derived from the literature and from data using an established cirrhosis cohort in the Veterans Health Administration. Participants included patients who were referred to a surgery clinic for a symptomatic abdominal hernia. Data were obtained from patients diagnosed with cirrhosis between January 1, 2008 and December 31, 2018. Data were analyzed from January 1 to May 1, 2022.Expected quality-adjusted life-years (QALYs) were estimated for each pathway and iterated over baseline model for end-stage liver disease-sodium (MELD-Na) scores ranging from 6 to 25. Markov models were cycled over a 5-year time horizon.A total 2740 patients with cirrhosis (median [IQR] age, 62 [56-66] years; 2699 [98.5%] men) were referred to a surgery clinic for a symptomatic abdominal hernia; 1752 patients (63.9%) did not receive surgery. The median (IQR) follow-up was 42.1 (25.3-70.0) months. Using this cohort to estimate the mortality risk of operative and nonoperative pathways, an initial MELD-Na threshold of 21.3 points, below which surgery was associated with maximized QALYs was identified. Nonoperative management was associated with increased QALYs above this MELD-Na threshold. Although more patients experienced death with a surgical treatment decision across all initial MELD-Na values, this was counterbalanced by increased time spent in a resolved hernia state associated with increased utility. Model results were sensitive to the probability of hernia recurrence and hernia incarceration and utility decrement in the symptomatic hernia state.This decision analytical model study found that elective surgical treatment for a symptomatic abdominal hernia was favored even in the setting of relatively high MELD-Na scores. Patient symptoms, hernia-specific characteristics, and surgeon and center expertise may potentially impact the optimal strategy, emphasizing the importance of shared decision-making.

Kidney transplantation at the time of a global viral pandemic has become challenging in many aspects. Firstly, we must reassess deceased donor safety (for the recipient) especially in communities with a relatively high incidence of coronavirus disease 19 (COVID-19). With respect to elective live donors, if one decides to do them at all, similar considerations must be made that may impose undue hardship on the donor. Recipient selection is also problematic since there is clear evidence of a much higher morbidity and mortality from COVID-19 for patients older than 60 and those with comorbidities such as hypertension, diabetes, obesity and lung disease. Unfortunately, many, if not most of dialysis patients fit that mold. We may and indeed must reassess our allocation policies, but this must be done based on data rather than conjecture. Follow-up routines must be re-engineered to minimize patient travel and exposure. Reliance on technology and telemedicine is paramount. Making this technology available to patients is extremely important. Modifying or changing immunosuppression protocols is controversial and not based on clinical studies. Nevertheless, we should reassess the need for induction therapy across the board for ordinary patients and the more liberal use of mammalian target of rapamycin inhibitors in transplant patients with proven infection.

Many obstacles may complicate renal transplant, the preferred treatment for end-stage renal disease. Anatomic anomalies are of special importance during surgery. Double inferior vena cava is a rare anomaly reported in 0.2% to 3% of the population and may complicate renal transplant in certain cases. We present a case of a 29-year-old man with end-stage renal disease who was scheduled for repeat kidney renal transplant from a living related donor. His transplant posed many challenges to the transplant team. These included (1) difficult access for dialysis, which required transhepatic insertion of a dialysis catheter, (2) anomalous inferior vena cava anatomy with a double inferior vena cava, (3) a blocked right inferior vena cava, and (4) a small blocked bridging vein connecting the right inferior vena cava to an additional left inferior vena cava. A stent was inserted into the bridging vein to allow venous drainage from the graft. During the transplant procedure, the donated kidney was transplanted into the left iliac fossa and anastomosed to the left external iliac vein. The surgery was successful, without major operative or postoperative complications. The patient was discharged with normal renal function and enjoys normal renal function 6 months after surgery. This case emphasizes the importance of pretransplant evaluation and preparation and the need for high index of suspicion for anatomic variants in donors and recipients.

Liver transplantation during the COVID-19 pandemic is challenging. Both donor and recipient issues can be influenced by the risks attributed to the pandemic. Allocation policy may need to be modified and criteria may be influenced by local infection rates and availability of medical facilities. Modifying immunosuppression (IS) protocols is controversial and is not evidence-based. In this study, we review the published literature on liver transplant recipients who were infected with COVID-19. A literature review was performed using PubMed, ScienceDirect, and WHO databases to identify relevant English-language articles published up to May 20, 2020. Fifteen articles reported 120 liver transplant recipients who were infected with COVID-19. Only 10 papers with 22 patients reported full encounter characteristics. Four papers reported 23, 17, 13, and 6 patients, respectively, but with minimal data. One paper reported the authors' own 39 patients' characteristics and demographics. The mean age was 58.2 years with 66% males. The most commonly reported presentations in descending order were fever (91%), cough (36.7%), shortness of breath (SOB) (31.8%), and diarrhea (31.8%). Liver transplant patients infected with COVID-19 were maintained on Tac (79%), mycophenolate (MMF) (48.4%), and Prednisone (29.6%) and were managed by reducing MMF in 14.3% of patients and reducing Tac in 14.3% of patients; 28.6% of patients needed ICU admission, 13.6% of patients had died, and the reported general population COVID-19 mortality rate was 3.4%. The clinical presentation of COVID-19 in liver transplant recipients may be different from the general population, with higher rates of severe disease, complications, and mortality.

Genomic DNA is packed by histone proteins that carry a multitude of post-translational modifications that reflect cellular transcriptional state. Cell-free DNA (cfDNA) is derived from fragmented chromatin in dying cells, and as such it retains the histones markings present in the cells of origin. Here, we pioneer chromatin immunoprecipitation followed by sequencing of cell-free nucleosomes (cfChIP-seq) carrying active chromatin marks. Our results show that cfChIP-seq provides multidimensional epigenetic information that recapitulates the epigenetic and transcriptional landscape in the cells of origin. We applied cfChIP-seq to 268 samples including samples from patients with heart and liver pathologies, and 135 samples from 56 metastatic CRC patients. We show that cfChIP-seq can detect pathology-related transcriptional changes at the site of the disease, beyond the information on tissue of origin. In CRC patients we detect clinically-relevant, and patient-specific information, including transcriptionally active HER2 amplifications. cfChIP-seq provides genome-wide information and requires low sequencing depth. Altogether, we establish cell-free chromatin immunoprecipitation as an exciting modality with potential for diagnosis and interrogation of physiological and pathological processes using a simple blood test.One Sentence SummaryChIP-seq of plasma-circulating nucleosomes (cfChIP-seq) from a simple blood test provides detailed information about gene expression programs in human organs, and cancer.

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients. Although the major symptom of this disorder is photosensitivity, rarely, it can cause progressive liver disease requiring liver transplantation (LT). However, LT is not curative and only bone marrow transplantation (BMT) can correct the underlying enzymatic defect. Because liver disease results from accumulation of protoporphyrin in the liver, LT without hematopoietic stem cell transplantation leaves the new liver at risk for similar EPP-related damage. A handful of pediatric patients undergoing sequential LT and stem cell transplantation have been described in the literature; however, to date none has been described in detail in adults. We report a case of an adult male with EPP and liver failure who successfully underwent a sequential liver and hematopoietic stem cell transplantation (HSCT).

Bariatric surgery dramatically improves glycemic control, yet the underlying molecular mechanisms remain controversial because of confounding weight loss. We performed sleeve gastrectomy (SG) on obese and diabetic leptin receptor–deficient mice (db/db). One week postsurgery, mice weighed 5% less and displayed improved glycemia compared with sham-operated controls, and islets from SG mice displayed reduced expression of diabetes markers. One month postsurgery SG mice weighed more than preoperatively but remained near-euglycemic and displayed reduced hepatic lipid droplets. Pair feeding of SG and sham db/db mice showed that surgery rather than weight loss was responsible for reduced glycemia after SG. Although insulin secretion profiles from islets of sham and SG mice were indistinguishable, clamp studies revealed that SG causes a dramatic improvement in muscle and hepatic insulin sensitivity accompanied by hepatic regulation of hepatocyte nuclear factor-α and peroxisome proliferator–activated receptor-α targets. We conclude that long-term weight loss after SG requires leptin signaling. Nevertheless, SG elicits a remarkable improvement in glycemia through insulin sensitization independent of reduced feeding and weight loss.

Concanavalin A (ConA) induces natural killer T (NKT) cell-mediated liver damage. Glucocerebroside (GC) is a naturally occurring glycolipid. Our aims were to determine the effect of GC in a murine model of ConA-induced hepatitis. Mice in groups A and B were treated with GC 2 h before and 2 h following administration of ConA, respectively; group C mice were treated with ConA; group D mice was treated with GC; group E mice did not receive any treatment. Liver damage was evaluated by serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels and liver histology. The immune effect of GC was determined by fluorescence-activated cell sorter analysis of intrahepatic and intrasplenic NKT lymphocytes, measurement of cytokine levels, and Western blot analysis for STAT 1, 4, 6, and NF-κB expression. The effect of GC on NKT cell proliferation was assessed in vitro. Serum AST and ALT levels were markedly reduced in GC-treated group A mice compared with nontreated group C animals, and histological damage was markedly attenuated in group A. The beneficial effect of GC was associated with a 20% decrease of intrahepatic NKT lymphocytes, significant lowering of serum IFN-γ levels, and decreased STAT1 and STAT6 expression. In vitro administration of GC led to a 42% decrease of NKT cell proliferation in the presence of dendritic cells but not in their absence. Intraperitoneally administered radioactive GC was detected in the liver and bowel. Administration of GC led to amelioration of ConA hepatitis associated with an inhibitory effect on NKT lymphocytes. GC holds promise as a new immune-modulatory agent.

Renal artery injuries are rarely encountered in victims of blunt trauma. However, the rate of early diagnosis of such injuries is increasing due to increased awareness and the liberal use of contrast-enhanced CT. Sporadic case reports have shown the feasibility of endovascular management of blunt renal artery injury. However, no prospective trials or long-term follow-up studies have been reported.To present our experience with endovascular management of blunt renal artery injury, and review the literature.We conducted a retrospective study of 18 months at a level 1 trauma center. Search of our electronic database and trauma registry identified three patients with renal artery injury from blunt trauma who were successfully treated endovascularly. Data recorded included the mechanism of injury, time from injury and admission to revascularization, type of endovascular therapy, clinical and imaging outcome, and complications.Mean time from injury to endovascular revascularization was 193 minutes and mean time from admission to revascularization 154 minutes. Stent-assisted angioplasty was used in two cases, while angioplasty alone was performed in a 4 year old boy. A good immediate angiographic result was achieved in all patients. At a mean follow-up of 13 months the treated renal artery was patent in all patients on duplex ultrasound. The mean percentage renal perfusion of the treated kidney at last follow-up was 36% on DTPA renal scan. No early or late complications were encountered.Endovascular management for blunt renal artery dissection is safe and feasible if an early diagnosis is made. This approach may be expected to replace surgical revascularization in most cases.

Cell-free DNA (cfDNA) in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells and retain some of the cell-of-origin histone modifications. In this study, we applied chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we showed that we can identify pathology-related changes in hepatocyte transcriptional programs. In patients with metastatic colorectal carcinoma, we detected clinically relevant and patient-specific information, including transcriptionally active human epidermal growth factor receptor 2 (HER2) amplifications. Altogether, cfChIP-seq, using low sequencing depth, provides systemic and genome-wide information and can inform diagnosis and facilitate interrogation of physiological and pathological processes using blood samples.