García, S. Gómez

Abstract Background: Chronic immunosuppression in solid organ transplant recipients leads to B- and T-cell depletion, which increases the risk of somatic driver mutations that drive monoclonal lymphocyte proliferation. Paradoxically, this impairs cellular immunity, leading to increased susceptibility to both bacterial and viral pathogens. Methods: This retrospective cohort study evaluated solid organ transplant recipients diagnosed with post-transplant lymphoproliferative disorder (PTLD) at the Cleveland Clinic Foundation between January 1, 2010, and December 30, 2021. Patients aged ≥18 years with infection data available for at least one-year post-PTLD diagnosis were included, excluding hematopoietic stem cell transplant recipients. Data on PTLD subtype, Epstein-Barr virus (EBV) status, infectious complications, and outcomes were analyzed using univariate analysis (Pearson’s χ² test) and multivariable logistic regression to identify predictors of infections and mortality. Results: Among 98 PTLD cases, the median onset was 7.03 years post-transplant. EBV-positive PTLD had an onset of 6.97 ± 7.21 years, whereas EBV-negative cases occurred later (8.06 ± 5.24 years). Monomorphic PTLD (94.9%), particularly diffuse large B-cell lymphoma (DLBCL, 63.3%), was predominant. Infections occurred in 60% of patients post-PTLD, with bacterial (41.25%), viral (31.66%), fungal (25.9%), and parasitic (1.19%) infections. At one year, infection-related mortality (48%) exceeded PTLD progression-related deaths (36%). Conclusion: PTLD presents with a complex interplay of immunosuppression, malignancy, and infection. Infections, particularly bacterial infections, are major causes of morbidity and mortality. These findings highlight the need for vigilant infectious disease surveillance and tailored interventions to reduce infection-related mortality and improve outcomes in high-risk populations.

Cardiotoxicity has been extensively reported in venlafaxine (VEN) overdoses. Asthenia is also among the common side effects described for this antidepressant. VEN is metabolized mainly by CYP2D6 and to a minor extent by CYP2C19 to the major active metabolite O-desmethylvenlafaxine (ODV). Altered pharmacokinetic parameters in patients with polymorphisms in the CYP2D6 and CYP2C19 genes that result in decreased enzymatic activity have been documented. Here we describe a patient case of VEN associated palpitations and asthenia. The patient takes VEN extended release 150 mg twice daily. Genotyping confirmed the patient is a poor metabolizer for CYP2D6 and an intermediate metabolizer for CYP2C19. We propose that the palpitations and asthenia are related to sustained VEN exposure due to reduced metabolism.