High-dose Methotrexate and Rituximab Induction Regimen In Immunocompetent Patients With Primary CNS Lymphoma: A Retrospective Single-Center Study of Survival Predictors

Purpose:Primary Central Nervous System Lymphoma (PCNSL) is an aggressive tumor that is confined to the CNS. Although the provision of high-dose methotrexate (HD-MTX) has remarkably improved outcomes in PCNSL patients, the optimal treatment regimens and standard MTX dose have been largely controversial. Herein, we sought to explore the impact of adjuvant Rituximab and different dosages of HD-MTX on survival outcomes of immunocompetent patients with PCNSL.Methods:In this study, we examined patients with PCNSL treated at a single NCI-designated comprehensive cancer center to evaluate their survival outcomes. We conducted a retrospective analysis of 51 immunocompetent patients with PCNSL who received their induction chemotherapy at the University of Alabama at Birmingham (UAB) between 2001 and 2019. Only adult patients with a confirmed diagnosis of PCNSL who had either HD-MTX alone or in combination with Rituximab were included. Patients’ demographics, clinical characteristics, and survival data were collected and analyzed.Results:There is no significant difference in survival among patients who received MTX alone versus MTX plus Rituximab. Furthermore, lower doses of MTX were associated with worse survival outcomes; however, this difference in survival was not significant when adjusted to age.Conclusion:Our experience challenges the role of Rituximab in PCNSL during induction therapy. Our study also highlights the shorter survival in elderly patients with PCNSL which can be related, to some extent, to the relatively lower doses of HD-MTX. There is an unmet need to establish a consensus on the most effective upfront regimen in PCNSL through prospective studies.

Inhibitory KIR2DL2 Receptor and HHV-8 in Classic or Endemic Kaposi Sarcoma

KIR2DL2, an inhibitory Killer cell Immunoglobulin-like Receptor (KIR), has been shown to predispose to the development of several herpesvirus-associated diseases by inhibiting the efficiency of Natural Killer (NK) cells against virus-infected cells. The aim of this observational study was to assess the prevalence of KIR2DL2 and Human Herpes Virus 8 (HHV8) in patients affected with classical and endemic Kaposi sarcoma (KS), as well as in controls. Blood samples collected from 17 Caucasian, HIV-negative, immunocompetent patients affected with classical KS (c-KS), 12 African, HIV-negative patients with endemic KS (e-KS), 83 healthy subjects and 26 psoriatic patients were processed for genotypization by PCR for two KIR alleles, such as KIR2DL2 and KIR2DL3 and analyzed for HHV-8 presence. The totality of both c-KS and e-KS patients presented HHV-8 infection, whereas HHV8 was found in 26.9% of psoriatic subjects and 19.3% of healthy subjects. KIR2DL2 was found in the 76.5% of c-KS subjects, while the receptor was found in 41.7% of the e-KS group, 34.6% of psoriatic patients and 43.4% of healthy controls (p<0.0001). A significantly higher prevalence of KIR2DL2 in c-KS patients than in all the other subjects was also confirmed comparing age-matched groups. Based on these results, the inhibitory KIR2DL2 genotype appears to be a possible cofactor which increases the risk of developing c-KS in HHV8-positive, immunocompetent subjects, while it seems less relevant in e-KS pathogenesis.

Acute Herpes Simplex Esophagitis in an Immunocompetent Adult with Eosinophilic Esophagitis

Herpes simplex esophagitis (HSE) represents a rare entity in immunocompetent patients and has infrequently been described in association with eosinophilic esophagitis (EoE). Causality in this rare association remains a debated topic. We present a case of HSE occurring in an immunocompetent adult with EoE and review the literature in support of EoE induced mucosal disruption predisposing to increased risk of HSE.

Using RNA-Seq to Investigate Immune-Metabolism Features in Immunocompromised Patients With Sepsis

Objective: Sepsis is life threatening and leads to complex inflammation in patients with immunocompromised conditions, such as cancer, and receiving immunosuppressants for autoimmune diseases and organ transplant recipients. Increasing evidence has shown that RNA-Sequencing (RNA-Seq) can be used to define subendotype in patients with sepsis; therefore, we aim to use RNA-Seq to identify transcriptomic features among immunocompromised patients with sepsis.Methods: We enrolled patients who were admitted to medical intensive care units (ICUs) for sepsis at a tertiary referral centre in central Taiwan. Whole blood on day-1 and day-8 was obtained for RNA-Seq. We used Gene Set Enrichment Analysis (GSEA) to identify the enriched pathway of day-8/day-1 differentially expressed genes and MiXCR to determine the diversity of T cell repertoire.Results: A total of 18 immunocompromised subjects with sepsis and 18 sequential organ failure assessment (SOFA) score-matched immunocompetent control subjects were enrolled. The ventilator-day, ICU-stay, and hospital-day were similar between the two groups, whereas the hospital mortality was higher in immunocompromised patients than those in immunocompetent patients (50.0 vs. 5.6%, p &lt; 0.01). We found that the top day-8/day-1 upregulated genes in the immunocompetent group were mainly innate immunity and inflammation relevant genes, namely, PRSS33, HDC, ALOX15, FCER1A, and OLR1, whereas a blunted day-8/day-1 dynamic transcriptome was found among immunocompromised patients with septic. Functional pathway analyses of day-8/day-1 differentially expressed genes identified the upregulated functional biogenesis and T cell-associated pathways in immunocompetent patients recovered from sepsis, whereas merely downregulated metabolism-associated pathways were found in immunocompromised patients with septic. Moreover, we used MiXCR to identify a higher diversity of T cell receptor (TCR) in immunocompetent patients both on day-1 and on day-8 than those in immunocompromised patients.Conclusions: Using RNA-Seq, we found compromised T cell function, altered metabolic signalling, and decreased T cell diversity among immunocompromised patients with septic, and more mechanistic studies are warranted to elucidate the underlying mechanism.

COVID - 19 Presenting with Fungal Infections - The Hidden Pandemic within Pandemic?

As the pandemic continues to spread vigorously, it is being noted that the COVID 19 virus is associated with various complications during the disease and also a great deal of post disease sequel.1 These gruelling complications are integrated with the overwhelming infection caused by the cytokine storm produced by the virus. While the treatment modalities are still under trial, glucocorticoids seem to have played a pivotal role in putting a check to the inflammation caused by the virus and have forbidden the organ damage caused thereafter. However, the aftermath of glucocorticoids usage has its own benefits and risks. Glucocorticoids cause cellular immunodeficiency and thus have immunosuppressive effects, additionally the use of immunomodulators such as tocilizumab alters the immune system and it subsequently predisposes the host to various secondary opportunistic infective agents. In the current state, as the pandemic abstains from fading away, an increasing trend of secondary fungal infections has been seen with COVID-19, resulting in an outbreak of fungal infections such as mucormycosis and candidiasis. Mucormycosis refers to any infection caused by the fungi of the Order Mucorales. Mucormycosis has been documented in the literature to be associated with a high rate of mortality due to its potential to spread drastically.2 Altered immunity is an important risk factor for mucormycosis. Additionally, diabetes has been noted to be critical for the development of mucormycosis in immunocompetent patients. Candidiasis is an infection caused by the candida species due to the immunosuppressed state developed by the use of glucocorticoids, which results in secondary fungal infection requiring urgent medical attention. The objective of this case report is to highlight the impending secondary fungal infection outbreak in COVID-19 and the need to contain this emerging spread of fungal infections under the blanket of this deadly pandemic.