OBJECTIVE:To evaluate national trends and clinical outcomes of donation after circulatory death (DCD) simultaneous liver-kidney transplantation (SLKT) in the US, particularly in the modern era following adoption of machine perfusion (MP) and normothermic regional perfusion (NRP). BACKGROUND:Utilization of DCD donors for liver transplantation has increased substantially in the US, and MP and NRP were reported to reduce complications, including reperfusion syndrome and early allograft dysfunction. However, national trends and outcomes of DCD-SLKT in the contemporary era of organ perfusion have not been characterized. METHODS:Using UNOS STAR files, we analyzed 10.687 adult primary SLKT performed between 2000 and 2025. Outcomes of DCD and donation after brain death (DBD) SLKT during 2020-2025 were compared using propensity score matching (PSM) to adjust for donor and recipient characteristics. Kaplan-Meier methods were used to assess graft/patient survival. RESULTS:The utilization of DCD-SLKT increased markedly after 2018, accounting for 29.3% of all SLKT cases in 2024. In 2024, liver MP, kidney MP, and NRP were used in 58.1%, 82.9%, and 40.1% of DCD-SLKT cases. Before matching, recipients in the DBD-SLKT group more frequently required dialysis at transplantation (69.1% vs 54.2%) and were hospitalized preoperatively (51.0% vs 17.2%), and had higher MELD scores (30 vs 23) during 2020-2025. Median follow-up was shorter in DCD-SLKT (706 vs 364 days), reflecting the more recent adoption of DCD transplantation. Liver graft/patient survival were comparable between DCD- and DBD-SLKT regardless of PSM. CONCLUSIONS:Utilization of DCD donors for SLKT has increased substantially in parallel with the expanding use of MP and NRP, with graft/patient outcomes comparable to those of DBD-SLKT regardless of PSM. However, DBD-SLKT recipients had higher baseline preoperative risk. These support broader adoption of DCD donors for SLKT in appropriately selected recipients.

Introduction In Solid Organ Transplant (SOT) recipients, due to immunosuppression, the immunogenicity after COVID-19 vaccination is suboptimal and its durability is unknown. Methods We conducted a post-hoc analysis of a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs JNJ-78436735 as the third dose after two doses of BNT162b2 in adult SOT recipients with active graft to compare long-term immunogenicity. Results Forty-one recipients were analyzed. Median IgG levels against SARS-CoV-2 at 6 months were 53,747 (range 949 – 657,558) and 7,632 (range 642 – 672,000) AU/ml for BNT162b2 vs JNJ-78436735, respectively (p=0.017). The median geometric mean fold increase ratio at 6 months was 37.2 (0.12-618.5) and 4.30 (0.1-204.2) for BNT162b2 vs JNJ-78436735, respectively (p<0.05). After two doses of BNT162b2, homologous approach with BNT162b2 achieved a superior immunogenicity compared to heterologous approach with JNJ-78436735. Conclusion In this post hoc analysis, we report durability of specific IgG between two vaccine strategies and found no statistically significant difference between two groups. (Clinical Trial Registry: NCT05047640)

Solid Organ Transplant (SOT) recipients are at significant higher risk for COVID-19 and due to immunosuppressive medication, the immunogenicity after vaccination is suboptimal. In the previous studies, booster method showed significant benefit in this population. In the current study, we compared using a mix-and-match method vs. same vaccine as a third dose in SOT recipients. This was a patient-blinded, single center, randomized controlled trial comparing BNT162b2 vs. JNJ-78436735 vaccine as the third dose after two doses of BNT162b2 vaccine. We included adult SOT recipients with functional graft who had received two doses of BNT162b2 vaccine. Participants were randomly assigned to receive either BNT162b2 or JNJ-78436735 in one-to-one ratio. Primary outcome was SARS-CoV-2 IgG positivity at 1 month after the third dose. Sixty SOT recipients, including 36 kidney, 12 liver, 2 lung, 3 heart, and 5 combined transplants, were enrolled, and 57 recipients were analyzed per protocol. There were no statistically significant differences between the two vaccine protocols for IgG positivity (83.3% vs. 85.2% for BNT162b2 and JNJ-78436735, respectively, p = 0.85, Odds Ratio 0.95, 95% Confidence Interval 0.23–4.00). Comparison of the geometric mean titer demonstrated a higher trend with BNT162b2 ( p = 0.09). In this pilot randomized controlled trial comparing mix and match method vs. uniform vaccination in SOT recipients, both vaccines were safely used. Since this was a small sample sized study, there was no statistically significant difference in immunogenicity; though, the mix and match method showed relatively lower geometric mean titer, as compared to uniform vaccine. Further studies need to be conducted to determine duration of this immunogenicity. Clinical Trial Registration : https://clinicaltrials.gov/ct2/show/NCT05047640?term=20210641&draw=2&rank=1 , identifier 20210641.

A of coronavirus disease 2019 (COVID19) vaccines is critical to ending the pandemic. The available mRNA vaccines are 94%–95% effective in preventing COVID-19 in the general population. Vaccineinduced antibody responses are reported to be lower in solid organ transplant recipients (SOTRs) compared with the general population; 17% after the first dose and 54% after the second dose, with poor response, are generally associated with the use of antimetabolite agents. In the United States, approximately 101 million persons are fully vaccinated with vaccine breakthrough infections reported in 10 262 (breakthrough rate 0.01%) as of April 30, 2021. Data on postvaccine infections in SOTRs are limited. We reported the largest series of vaccine breakthrough COVID-19 infections in SOTRs in the United States (the study approved by the University of Miami Institutional Review Board). Twenty-six patients were diagnosed with COVID-19 infection by nasopharyngeal polymerase chain reaction, after receiving 1 (n = 3, 12%) or both (n = 23, 89%) doses of BNT162b2 (Pfizer-BioNTech) vaccine. They had no prior COVID-19 infection. The mean age at the time of vaccination was 58 y (32–81); 54% were males and 72% were of Hispanic ethnicity. Eleven patients (42.3%) reported exposure to unvaccinated family members with COVID-19. The median time from transplant to the vaccine (first dose) was 31 mo (range, 0.7–272), with 4 (15.3%) within 6 mo of transplant, and from vaccine to diagnosis was 34 d (range, 4–96). Antibody testing targeting the spike protein was performed via the VITROS test to measure immunoglobulin G and total antibodies (Table 1). All patients were symptomatic. Thirteen patients (50%) required hospital admission and were treated with remdesivir (92.3%, n = 12), high-dose steroids (84.6%, n = 11), and therapeutic plasma exchange (23%, n = 3; only for refractory cases in cytokine storm). Twelve patients (46%) were managed outpatient with early administration of monoclonal antibodies (MABs; casirivimab/imdevimab); all recovered with no progression of the disease. Two (16.6%) were admitted within 28 d of receiving MABs for non–COVID-19 issues. At a median follow-up of 28.5 d (range, 2–75), 5 (19.2%) had severe COVID-19 and 2 (7.6%) patients died. None of them developed rejection or graft loss. As of April 30, 2021, 2957 SOTRs have been vaccinated at our center, with 26 cases of vaccine breakthrough infection (breakthrough rate 0.87%), which is higher than that reported in the general population. Our findings confirmed that severe COVID-19 and mortality can occur from vaccine breakthrough infections in SOTRs. Data show transplant patients developed cellular and humoral responses despite immunosuppression, suggesting that vaccinated SOTRs may benefit from the vaccine even in the absence of antibody response. In conclusion, SOTRs remain at risk of severe COVID19 even after the vaccination. Vaccinating SOTRs and ring vaccination of close contacts may provide better protection to immunocompromised patients. Transplant centers should continue to reinforce social distancing, mask use, and handwashing in fully vaccinated SOTR, even though mask mandates are relaxed nationally. Multicenter studies assessing cellular and humoral immunogenicity data, role of booster doses, use of MABs as prophylaxis in adjunct to vaccines, and genomic sequencing to identify variants causing vaccine breakthrough infections are needed.

Aim of the study To determine whether liver-directed therapies (LDT) and no therapy affect waiting list times for liver transplant candidates from a single center. Material and methods This retrospective study included patients > 12 years of age diagnosed with hepatocellular carcinoma between January 2014 and June 2019 and followed until the date of transplant, date of delisting, loss to follow-up, or date of death. Waiting list time and associated factors were analyzed using Kaplan-Meier and Cox proportional-hazards methods. Results A total of 181 patients met the selection criteria. The mean age was 60 years with standard deviation (SD) of 7.8 years. Sixty-six percent underwent transplant, and 64% were classified within the Milan criteria. Men had a lower median waiting list time than women (191 days vs. 236 days, p = 0.0093). The overall median survival time or time to transplant for 50% of the population was 218 days (95% CI: 195-235). Men displayed a 3.1-fold (95% CI: 1.5-6.2) higher probability of transplantation than women (p = 0.002). Patients who received no therapy had a 5-fold higher probability of undergoing transplantation than patients under arterial LDT (HR [95% CI]: 5 [1.2, 20], p = 0.02). Patients under combined LDT displayed a 70% reduced probability of transplantation compared to patients who received arterial LDTs (p = 0.0009). Conclusions LDT was associated with a prolonged stay on the transplant list, likely due to the presence of an aggressive liver tumor. However, LDTs allow the patient to remain active on the liver transplant list, increasing their chances of undergoing transplantation.

BACKGROUND:Magnesium (Mg) deficiency contributes to the pathophysiology of numerous diseases. The therapeutic use of Mg has steadily increased over time. The increased in-hospital use of intravenous (IV) magnesium sulfate (MgSO4) warrants more extensive investigation regarding the safety of the therapy. The aim of this study was to determine the safety of IV MgSO4 infusion on cardiovascular, liver, kidney, and metabolic markers in adults.METHODS:Twelve volunteers were randomized to one of two cross-over conditions: (a) IV infusion of MgSO4 in 5% dextrose followed by IV infusion of 5% dextrose 1 week later or (b) IV infusion of 5% dextrose followed by IV infusion of MgSO4 in 5% dextrose 1 week later. An electrocardiogram was recorded continuously during the infusions. Blood was drawn pre- and post-infusion for blood count (high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides). Results: Serum Mg increased from pre- to post-infusion in the MgSO4 + 5% dextrose group (p < 0.0001). The QRS interval length increased from pre- to post-infusion in the MgSO4 + 5% dextrose group (p < 0.04). Additionally, serum glucose concentration increased in the MgSO4 + 5% dextrose group (p = 0.04). These significant findings were modeled with gender and age as covariates. No other significant differences were found.CONCLUSIONS:The administration of IV infusion of MgSO4 (4 g/100 mL) in 5% dextrose over a 4-hour treatment period poses no significant deleterious effects on cardiovascular, liver, kidney, or metabolic function.RELEVANCE FOR PATIENTS:IV infusion of MgSO4 may be used for certain treatment indications without significant concern for systemic or organ toxicity.

Autoinfection caused by Strongyloides stercoralis frequently becomes a life-long disease unless it is effectively treated. There is overlapping histomorphology between Strongyloides colitis and inflammatory bowel disease; a low index of suspicion can lead to misdiagnosis and fatal consequences. We present a case of Strongyloides colitis mimicking the clinical and pathologic features of inflammatory bowel disease. A 64-year-old female presented to the emergency department with a four-day history of abdominal pain, diarrhea, and hematochezia. Colonoscopy revealed diffuse inflammation suggestive of inflammatory bowel disease, which led to initiation of 5-aminosalicylic acid and intravenous methylprednisolone. Biopsies of the colon revealed increased lymphoplasmacytic infiltrate of the lamina propria with eosinophilic microabscesses and presence of larvae, consistent with Strongyloides stercoralis. Immunosuppressive medication was halted. The patient ultimately died a few days later. This case emphasizes the importance of identifying the overlapping clinical and pathologic features of Strongyloides colitis and inflammatory bowel disease. A high index of suspicion and recognition of particular histological findings, including eosinophilic microabscesses, aid in the correct diagnosis. Definitive diagnosis is crucial as each disease carries distinct therapeutic implications and outcome.

Introduction: Gastroesophageal varices are a common complication of portal hypertension, present in approximately 50% of patients with cirrhosis. Variceal hemorrhage occurs at a yearly rate of 5-15% in patients with cirrhosis. Despite improvements in medical & endoscopic therapy, variceal hemorrhage still carries a 20% mortality. This outcome is likely multifactorial; however, it could be related to suboptimal identification & resultant inadequate treatment of esophageal varices (EV). Use of a through-the-scope (TTS) Doppler ultrasound probe has been used in management of non-variceal hemorrhage for identification of vessels. The aim of this report is to present 2 cases with novel use of a TTS Doppler ultrasound probe to guide identification & management of EV. Methods: TTS Doppler ultrasound system (VTI, Nashua, NH) was used at mid-depth setting (0-4mm) with light pressure. Following band ligation, Doppler probe was applied 1cm proximal to band. Case 1: 71 year old woman with PBC cirrhosis & known small EV on beta-blockers without history of banding underwent EGD. Two protruding vascular-appearing lesions were identified in the middle third of the esophagus, suspicious for EV. A TTS Doppler probe was applied to the lesions with no auditory signal, indicating no vascular flow within the lesion. These suspected EV were identified as venous blebs, & no intervention was pursued. Case 2: 58 year old man with alcoholic & NASH cirrhosis with EV underwent EGD for EV surveillance. He had EV banding 1 month prior with reported proximal decompression. EGD revealed 2 chains of Grade II EV in the distal third of the esophagus. TTS Doppler ultrasound probe was used to confirm flow by placing the probe over the lesions. Auditory signal of Doppler flow was confirmed in the 2 endoscopically visualized chains. Moreover, the Doppler probe identified an unsuspected third chain of EV that was not endoscopically visible & which may be part of the submucosal plexus of veins & perforators. Three bands were successfully placed. The TTS Doppler probe was reapplied to confirm eradication of flow in all 3 chains. No signal was identified proximally. Discussion: These 2 cases highlight applications of the TTS Doppler ultrasound probe for EV, which has potential to impact variceal screening & bleeding management by identifying blood flow in suspected, & perhaps more importantly, in unsuspected EV. Further prospective studies are warranted to investigate the role of this modality in the management of EV.

A 48-year-old Egyptian woman presented with 8 months of sharp right upper chest pain and weight loss. She was discovered to have an enlarged cardiac silhouette on chest x-ray, and an echocardiogram revealed a large pericardial effusion with diastolic right atrial collapse. Pericardial window was done, and epithelial membrane antigen-positive neoplastic cells were identified in the pericardial fluid. Computed tomography showed a 6-cm hypermetabolic lesion on the liver segment IV, confirmed on biopsy to be a moderately differentiated adenocarcinoma consistent with intrahepatic cholangiocarcinoma.

AimTreatment‐resistant depression patients are more likely to suffer from comorbid physical and mental disorders, experience marked and protracted functional impairment, and incur higher health‐care costs than non‐affected individuals. Magnesium sulfate is a treatment option that may offer great potential for patients with treatment‐resistant depression based on prior work in animals and humans.MethodsTwelve subjects with mild or moderate treatment‐resistant depression were randomized into a double‐blind crossover trial to receive an infusion of 4 g of magnesium sulfate in 5% dextrose or placebo infusion of 5% dextrose with a 5‐day washout in between the 8‐day intervention period. Subjects were assessed before and after the intervention for serum and urine magnesium, lipid panel, the Hamilton Rating Scale for Depression, and the Patient Health Questionnaire‐9.ResultsWe found a difference in serum magnesium from day 2 to 8 (pre‐infusion) (P < 0.002) and from baseline to day 8 (P < 0.02). No changes were noted on the Hamilton Rating Scale for Depression or the Patient Health Questionnaire‐9 24 h post‐treatment, but as serum magnesium increased from baseline to day 7, the Patient Health Questionnaire‐9 decreased from baseline to day 7 (P = 0.02).ConclusionMagnesium sulfate did not significantly affect depression 24 h post‐infusion, but other results were consistent with the literature. The association between changes in serum magnesium and the Patient Health Questionnaire‐9 supports the idea that magnesium sulfate may be used to address treatment‐resistant depression, an ongoing medical challenge.

Introduction: Hypervitaminosis A is a known, yet rare, cause of postsinusoidal portal hypertension. We describe a case of a man who presented with anasarca after vitamin A megadosing. A 47-year-old man without prior medical history presented with 3 weeks of increasing abdominal girth, lower extremity edema, dyspnea, and orthopnea. He was taking high doses of multiple nutritional supplements for 5 years, including 120,000 IU of vitamin A per day, but no medications. He denied tobacco, alcohol, or recreational drugs. He appeared cachectic. Right-sided breath sounds were decreased with dullness to percussion. He had a distended abdomen with shifting dullness and an indurated liver edge palpable 5 cm below the costal margin. His spleen was not palpable. He had lower extremity edema, but no other stigmata of chronic liver disease. On presentation, laboratory data showed abnormal liver tests (protein 6.0 g/dL, albumin 2.9 g/dL, total bilirubin 1.3 mg/dL, AST 49 u/L, ALT 31 u/L, alkaline phosphatase 136 u/L, INR 1.2, creatinine 0.81 mg/dL, and platelets 357,000/mm3). Hepatitis A, B, and C serologies and markers for autoimmune hepatitis and PBC were negative. There was no evidence of genetic or metabolic diseases. Abdominal ultrasound showed ascites, hepatomegaly, and patent suprahepatic veins. Paracentesis revealed a total protein of 4.4 g/dL and serum ascites albumin gradient of 1.7 g/dL. Echocardiogram was normal except for a mild pericardial effusion. A liver biopsy showed parenchyma with glycogenated nuclei, centrilobular lipofuscin, prominent stellate cells with vacuolization, mild lymphocytic portal inflammation, and centrilobular sinusoidal dilation with perivenular fibrosis. Trichrome stain showed periportal, centrilobular, and perisinuosidal fibrosis. Smooth muscle actin immunostain highlighted the vacuolated stellate cells. These findings suggested hypervitaminosis A. The patient discontinued vitamin A 2 months after presentation, but continued to deteriorate with worsening ascites, hepatic hydrothorax, encephalopathy, and SBP. He died 8 months after presentation. Vitamin A is known to cause peri- and postsinusoidal fibrosis after prolonged daily doses >25,000 IU. Literature regarding chronic ingestion in adults is scant. Most cases are potentially reversible, although some progress relentlessly despite cessation of vitamin A. Patients with decompensated liver disease tend to have a worse prognosis, and portal hypertension may occur in the absence of cirrhosis. Continued deterioration after cessation may be due to bioaccumulation and slow tissue turnover (half-life: 58-286 days). Hypervitaminosis A should be considered in the differential diagnosis of portal hypertension of obscure origin.

Since the adoption of the Model for End-Stage Liver Disease, simultaneous liver/kidney transplants (SLKT) have substantially increased. Recently, unfavorable outcomes have been reported yet contributing factors remain unclear. We retrospectively reviewed 74 consecutive adult SLKT performed at our center from 2000 to 2010 and compared with kidney transplant alone (KTA, N = 544). In SLKT, patient and death-censored kidney graft survival rates were 64 ± 6% and 81 ± 5% at 5 years, respectively (median follow-up, 47 months). Multivariable analyses revealed three independent risk factors affecting patient survival: hepatitis C virus positive (HCV+, hazard ratio [HR] 2.9, 95% confidence interval [CI] 1.1–7.9), panel reactive antibody (PRA) > 20% (HR 2.8, 95% CI 1.1–7.2) and female donor gender (HR 2.9, 95% CI 1.1–7.9). For death-censored kidney graft survival, delayed graft function was the strongest negative predictor (HR 8.3, 95% CI 2.5–27.9), followed by HCV+ and PRA > 20%. The adjusted risk of death-censored kidney graft loss in HCV+ SLKT patients was 5.8 (95% CI 1.6–21.6) compared with HCV+ KTA (p = 0.008). Recurrent HCV within 1 year after SLKT correlated with early kidney graft failure (p = 0.004). Careful donor/recipient selection and innovative approaches for HCV+ SLKT patients are critical to further improve long-term outcomes.

The editorial team of Digestive Diseases and Sciences (DDS) wishes to acknowledge the critically important role played by the individuals whose names appear in the following list of reviewers for calendar year 2010. Manuscript reviews by these research scientists and clinical investigators, as well as by members of the editorial board, are the cornerstone of the journal and vital to maintaining and improving the quality of DDS. The editorial team of DDS would like to further acknowledge those reviewers who also contributed editorials related to the manuscript that was reviewed; these critical analyses have provided important perspectives on the impact of the published article.

INTRODUCTION:We investigated the outcomes of adult liver transplants, according to their donor-recipient cytomegalovirus (CMV) serology.MATERIALS AND METHODS:We included in the study all adult primary liver transplants, from January 1, 2002, to December 31, 2005. Follow-up was until December 31, 2007. According to the donor-recipient CMV serology, patients were divided into positive-negative (PN), positive-positive, negative-negative, and negative-positive groups, and all received CMV prophylaxis for 4 months posttransplantation. Hepatitis C patients received conventional immunosuppression, whereas all other patients received either conventional treatment or alemtuzumab (Campath-1H) induction.RESULTS:We studied 438 adult liver transplants. Comparisons were made between high-risk group patients (PN) versus all others: 5-year patient survival was 74.31% vs. 78.8%, (P=NS) and graft survival 63.87% vs. 74.77%, (P=0.042). Five-year freedom from rejection was 42.84% vs. 51.95% (P=0.036). CMV infection (n=3) or disease (n=27) was observed in 30 patients (PN [n=23], positive-positive [n=6], and negative-positive [n=1]). Incidence of CMV infection was 9.8% overall and 34.84% and 2.5%, respectively, for the PN group versus all others (P=0.0000). Patients who received Campath-1H induction did not have an increased incidence of CMV infections compared with those who received conventional immunosuppression.CONCLUSIONS:In our center, in adult liver transplantation, CMV donor-recipient PN serology is associated with rejection, graft survival, and CMV infection but is not correlated with patient survival, Epstein-Barr virus (EBV) occurrence, or viral hepatitis recurrence. The introduction of more potent induction immunosuppression did not accentuate these negative outcomes.