A Pilot Single-Blinded, Randomized, Controlled Trial Comparing BNT162b2 vs. JNJ-78436735 Vaccine as the Third Dose After Two Doses of BNT162b2 Vaccine in Solid Organ Transplant Recipients.

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.

When is it safe to perform abdominal transplantation in patients with prior SARS-CoV-2 infection: A case series.

BACKGROUND: The Coronavirus disease 2019(COVID-19) pandemic has negatively impacted worldwide organ transplantation. However, there is limited information on recipients transplanted after SARS-CoV-2 infection. A full understanding of this scenario is required, as transplantation is a life-saving procedure and COVID-19 remains an ongoing threat. METHODS: Abdominal organ transplant recipients diagnosed with COVID-19 prior to transplantation were identified by chart review and clinical data were collected. The primary outcome was the transplant outcome including graft loss, rejection and death, and reactivation of infection post-transplant. RESULTS: We identified 14 patients who received abdominal organ transplants after symptomatic PCR confirmed SARS-CoV-2 infection; four patients had a positive PCR at the time of admission for transplantation. The median time of follow-up was 79 (22-190) days. One recipient with negative PCR before transplant tested positive 9 days after transplant. One of 14 transplanted patients developed disseminated mold infection and died 86 days after transplant. During the follow-up, only one patient developed rejection; thirteen patients had favorable graft outcomes. CONCLUSIONS: We were able to perform abdominal transplantation for patients with COVID-19 before transplant, even with positive PCR at the time of transplant. Larger studies are needed to determine the time to safe transplant after SARS-CoV-2 infection.

Double-blind, randomized crossover study of intravenous infusion of magnesium sulfate versus 5% dextrose on depressive symptoms in adults with treatment-resistant depression.

AIM: Treatment-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. METHODS: Twelve 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. RESULTS: We 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). CONCLUSION: Magnesium 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.

Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma: outcome after liver transplantation.

BACKGROUND: Combined hepatocellular carcinoma and intrahepatic cholangiocarcinoma is a rare hepatobiliary malignancy incorporating components derived from both hepatocyte and intrahepatic bile duct epithelium. The natural history, treatment, and prognosis of this distinct cancer differ from hepatocellular carcinoma (HCC) or cholangiocarcinoma (CC) and are not completely understood. There is considerable controversy about the classification, treatment, and survival, which in turn is related to the rarity of the condition. Treatment options include surgical resection and the prognosis is believed to be better than CC but worse than HCC alone. METHODS: We report a single-center liver transplantation experience with the management of three patients with combined HCC-ICC with LT. Two patients were transplanted with presumed HCC within Milan criteria and the other patient was noted to have an incidental nodule in the explanted liver. Histomorphology and immunohistochemical studies revealed the presence of combined HCC-ICC in all three explants. RESULTS: One patient died 144 days after LT due to metastatic tumor. The second patient is alive and is tumor free at 8.5 years post-LT, and the third patient died of metastatic tumor at 155 days after LT. CONCLUSION: Good long-term survival can be achieved in at least some patients with this combined tumor type.

Impact of liver-directed therapy and non-therapy on the waiting time list of patient candidates for liver transplantation: retrospective survival analysis.

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.

Intravenous infusion of magnesium sulfate is not associated with cardiovascular, liver, kidney, and metabolic toxicity in adults.

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.

Strongyloides Colitis as a Harmful Mimicker of Inflammatory Bowel Disease.

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.

Recurrent Cardiac Tamponade: An Unusual Presentation of Intrahepatic Cholangiocarcinoma.

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.

A Rare Case of Hepatitis C-Associated Cryoglobulinemic Duodenal Vasculitis.

Intestinal involvement of cryoglobulinemia is an uncommon manifestation and marker of severe vasculitis. We describe the case of a woman admitted to our service for management of acute renal failure and progressive gastrointestinal symptoms after initiating hepatitis C virus treatment with ribavirin and sofosbuvir 4 weeks prior. With an undetectable hepatitis C viral load and persistent symptoms despite hepatitis C virus therapy cessation, an upper endoscopy revealed duodenal sloughing, erythema, and bleeding, sparking suspicion for recurrence of cryoglobulinemic vasculitis.

The effect of donor-recipient cytomegalovirus serology on adult liver transplantation: a single center experience.

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.

Propylthiouracil-induced acute liver failure: role of liver transplantation.

Propylthiouracil- (PTU-) induced hepatotoxicity is rare but potentially lethal with a spectrum of liver injury ranging from asymptomatic elevation of transaminases to fulminant hepatic failure and death. We describe two cases of acute hepatic failure due to PTU that required liver transplantation. Differences in the clinical presentation, histological characteristics, and posttransplant management are described as well as alternative therapeutic options. Frequent monitoring for PTU-induced hepatic dysfunction is strongly advised because timely discontinuation of this drug and implementation of noninvasive therapeutic interventions may prevent progression to liver failure or even death.

Successful treatment of autoimmune hepatitis and idiopathic thrombocytopenic purpura with the monoclonal antibody, rituximab: case report and review of literature.

Rituximab, a chimeric monoclonal anti-CD20 antibody, has shown activity in several autoimmune disorders. We describe a case of a 52 years old female who was diagnosed with idiopathic thrombocytopenic purpura and concomitant autoimmune hepatitis (AIH), both non-responsive to steroids. She was subsequently treated with rituximab, which resulted in a rapid increase in her platelet count and an unexpected normalization of her hepatic biochemical tests. Both her platelet count and her hepatic biochemical tests remained normal for over 5 months. In this case, rituximab showed an impressive clinical response for the treatment of AIH, and it may be considered as an alternative treatment in patients who do not respond to corticosteroid therapy. Prospective randomized studies in AIH are needed to validate this observation.