Recent Advances in Adult Post-Transplant Lymphoproliferative Disorder

PTLD is a rare but severe complication of hematopoietic or solid organ transplant recipients, with variable incidence and timing of occurrence depending on different patient-, therapy-, and transplant-related factors. The pathogenesis of PTLD is complex, with most cases of early PLTD having a strong association with Epstein-Barr virus (EBV) infection and the iatrogenic, immunosuppression-related decrease in T-cell immune surveillance. Without appropriate T-cell response, EBV-infected B cells persist and proliferate, resulting in malignant transformation. Classification is based on the histologic subtype and ranges from nondestructive hyperplasias to monoclonal aggressive lymphomas, with the most common subtype being diffuse large B-cell lymphoma-like PTLD. Management focuses on prevention of PTLD development, as well as therapy for active disease. Treatment is largely based on the histologic subtype. However, given lack of clinical trials providing evidence-based data on PLTD therapy-related outcomes, there are no specific management guidelines. In this review, we discuss the pathogenesis, histologic classification, and risk factors of PTLD. We further focus on common preventive and frontline treatment modalities, as well as describe the application of novel therapies for PLTD and elaborate on potential challenges in therapy

The Risk of Immunosuppression: A Case of Salmonella Meningitis

Salmonella meningitis is a rare infection, particularly in adults. We report the case of a 75-year-old female with a history of rheumatoid arthritis on TNF-antagonist immunosuppressive therapy who initially presented to the hospital for management of back and leg pain and was ultimately diagnosed with bacterial meningitis secondary to Salmonella species infection. She was treated with ceftriaxone with slow improvement in neurological function. Though the source of infection was never clearly identified from multiple imaging studies, we suspect the severity of her presentation was due to her history of TNF-antagonist use

Optimizing the AKI definition during first postnatal week using Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) cohort.

BACKGROUND: Neonates with serum creatinine (SCr) rise ≥0.3 mg/dL and/or ≥50% SCr rise are more likely to die, even when controlling for confounders. These thresholds have not been tested in newborns. We hypothesized that different gestational age (GA) groups require different SCr thresholds. METHODS: Neonates in Assessment of Worldwide Acute Kidney Epidemiology in Neonates (AWAKEN) with ≥1 SCr on postnatal days 1-2 and ≥1 SCr on postnatal days 3-8 were assessed. We compared the mortality predictability of SCr absolute (≥0.3 mg/dL) vs percent (≥50%) rise. Next, we determine usefulness of combining absolute with percent rise. Finally, we determined the optimal absolute, percent, and maximum SCr thresholds that provide the highest mortality area under curve (AUC) and specificity for different GA groups. RESULTS: The ≥0.3 mg/dL rise outperformed ≥50% SCr rise. Addition of percent rise did not improve mortality predictability. The optimal SCr thresholds to predict AUC and specificity were ≥0.3 and ≥0.6 mg/dL for ≤29 weeks GA, and ≥0.1 and ≥0.3 mg/dL for \u3e29 week GA. The maximum SCr value provides great specificity. CONCLUSION: Unique SCr rise cutoffs for different GA improves outcome prediction. Percent SCr rise does not add value to the neonatal AKI definition

Incidence and Risk Factors of Early Onset Neonatal AKI

Background and objectives Neonatal AKI is associated with poor short-and long-term outcomes. The objective of this study was to describe the risk factors and outcomes of neonatal AKI in the first postnatal week. Design, setting, participants, & measurements The international retrospective observational cohort study, Assessment of Worldwide AKI Epidemiology in Neonates (AWAKEN), included neonates admitted to a neonatal intensive care unit who received at least 48 hours of intravenous fluids. Early AKI was defined by an increase in serumcreatinine. 0.3mg/dl or urine output, 1ml/kg per hour on postnatal days 2-7, the neonatalmodification of KidneyDisease: ImprovingGlobalOutcomes criteria. We assessed risk factors forAKI and associations ofAKI with death and duration of hospitalization. ResultsTwenty-onepercent (449of 2110) experiencedearlyAKI. EarlyAKIwas associatedwithhigher riskof death (adjusted odds ratio, 2.8; 95% confidence interval, 1.7 to 4.7) and longer duration of hospitalization (parameter estimate: 7.3 days 95% confidence interval, 4.7 to 10.0), adjusting for neonatal and maternal factors along with medication exposures. Factors associated with a higher risk of AKI included: outborn delivery; resuscitation with epinephrine; admission diagnosis of hyperbilirubinemia, inborn errors of metabolism, or surgical need; frequent kidney function surveillance; and admission to a children's hospital. Those factors that were associated with a lower risk includedmultiplegestations, cesarean section, andexposuresto antimicrobials, methylxanthines, diuretics, and vasopressors. Risk factors varied by gestational age strata. Conclusions AKI in the first postnatal week is common and associated with death and longer duration of hospitalization. The AWAKEN study demonstrates a number of specific risk factors that should serve as "red flags" for clinicians at the initiation of the neonatal intensive care unit course