Epstein-Barr virus (EBV) is linked to lymphoma and epithelioma but lacks drugs specifically targeting EBV-positive tumors. BamHI A Rightward Transcript (BART) miRNAs are expressed in all EBV-positive tumors, suppressing both lytic infection and host cell apoptosis. We identified suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylase enzymes, as an agent that suppresses BART promoter activity and transcription of BART miRNAs. SAHA treatment demonstrated a more pronounced inhibition of cell proliferation in EBV-positive cells compared to EBV-negative cells, affecting both p53 wild-type and mutant gastric epithelial cells. SAHA treatment enhanced lytic infection in wild-type EBV-infected cells, while also enhancing cell death in BZLF1-deficient EBV-infected cells. It reduced BART gene expression by 85% and increased the expression of proapoptotic factors targeted by BART miRNAs. These findings suggest that SAHA not only induces lytic infection but also leads to cell death by suppressing BART miRNA transcription and promoting the apoptotic program.

Tumor lysis syndrome (TLS) remains a debilitating cause of hospitalization and death in patients with cancer and is a significant challenge for healthcare providers despite advancements in its management. This umbrella review analyzed the results of meta-analyses on the use of rasburicase in the treatment of patients with cancer. A literature search was performed of five databases (PubMed, Google Scholar, Cochrane Library, Scopus, Global Index Medicus, and ScienceDirect) for articles with full texts available online. A measurement tool to assess systematic reviews 2 (AMSTAR 2) was used to assess the quality of the included studies, and Review Manager software was used to conduct all statistical analyses. The systematic search identified eight relevant meta-analyses, with primary analyses including outcome data that analyzed mortality, renal failure, and comparisons with allopurinol. The pooled data showed that rasburicase effectively reduced TLS development and serum uric acid levels in children and adults with malignancies. Most outcomes did not differ significantly compared with those of allopurinol. Future trials should focus on the cost-effectiveness of rasburicase compared to that of allopurinol while including high-, intermediate-, and low-risk patients. Rasburicase is safe and effective for managing patients with TLS. However, recent large-scale meta-analyses have reported conflicting results. Most meta-analyses were graded as low to critically low as per AMSTAR 2. The analysis revealed that the benefit of rasburicase did not differ significantly from that of allopurinol, which has higher cost-effectiveness and fewer side effects.

UNASSIGNED: Tumor lysis syndrome (TLS) is often diagnosed in children with hematological malignancies and can be life threatening due to metabolic disturbances. Continuous renal replacement therapy (CKRT) can reverse these disturbances relatively quickly when conventional medical management fails. Our objective was to investigate the benefit of CKRT in the management of TLS in children admitted to the intensive care unit with hematologic malignancies. In addition, we sought to assess risk factors for acute kidney injury (AKI) in the setting of TLS.
UNASSIGNED: Retrospective review of all children admitted to the intensive care unit with TLS who received CKRT from January 2012 to August 2022.
UNASSIGNED: Among 222 children hospitalized with TLS from January 2012 to August 2022, 20 (9%) underwent CKRT to manage TLS in the intensive care unit. The patients\' median age was 13 years (range 3-17 y), and most were males (18/20). T-cell acute lymphoblastic leukemia was the most common diagnosis (n=10), followed by acute myeloid leukemia (n=4), Burkitt lymphoma (n=4), and B-cell acute lymphoblastic leukemia (n=2). Five patients required mechanical ventilation, and 2 required vasopressors. The most common indication for CKRT was hyperphosphatemia, followed by, hyperuricemia, and hyperkalemia. All metabolic abnormalities corrected within 12 h of initiation of CKRT. CKRT courses were brief, with a median duration of 2 days (range 1-7 days). Having higher serum phosphorus levels 12 h preceding CKRT was significantly associated with severe acute kidney injury (AKI). The median phosphorus level was 6.4 mg/dL in children with no/mild AKI and 10.5 mg/dL in children with severe AKI (p=0.0375). Serum uric acid levels before CKRT were not associated with AKI. All children survived to hospital discharge, and the one-year survival rate was 90%.
UNASSIGNED: CKRT is safe in children with hematologic malignancies with severe TLS and reverses metabolic derangements within 6-12 h. Most patients had AKI at the initiation of CKRT but did not require long-term kidney replacement therapy. Hyperphosphatemia before initiation of CKRT is associated with higher risk of AKI.

A growing number of patients are living with cancer or have a history of cancer leading to increasing adverse effects of treatment or disease necessitating emergency department (ED) consultation. Long-term cancer survivors are at higher risk of comorbidities causing a substantial increase in health care resource utilization. The most frequent reasons for cancer-related ED visits are dyspnea, fever, pain, gastrointestinal or neurological symptoms leading to high hospital and intensive care unit admission rates. Acute respiratory failure in cancer patients necessitates timely diagnostic testing, whereby computed tomography is superior to chest X‑ray. Delay in intensive care unit (ICU) admission or mechanical ventilation increases mortality. Febrile neutropenia is an emergency with urgent need for antibiotic treatment. Treatment of neutropenic and nonneutropenic patients with sepsis does not differ. Cardiovascular disease is now the second leading cause of long-term morbidity and mortality among cancer survivors. Immunotherapy can lead to substantial and in some patients life-threatening complications that may not easily be recognized in the ED. Cancer-specific emergencies such as leukostasis, tumorlysis or hypercalcemia rarely present to ED and require interdisciplinary care. The constantly growing cancer population is likely to increase ED utilization. Knowledge about cancer treatment and disease-associated complications is crucial for emergency physicians. Palliative care education should secure appropriate end-of-life care avoiding futile interventions.
UNASSIGNED: Die Anzahl der mit einer malignen Grunderkrankung lebenden Patienten steigt stetig an. Damit verbundene krankheits- oder therapieassoziierte Komplikationen sowie die aufgrund des zunehmenden Lebensalters manifesten Komorbiditäten führen zu einer erheblichen und steigenden Inanspruchnahme akut- und notfallmedizinischer Ressourcen. Krebspatienten konsultieren Notaufnahmen zumeist mit Abgeschlagenheit, Dyspnoe, Fieber, Schmerzen, gastrointestinalen oder neurologischen Symptomen. Die Hospitalisierungs- und Intensivstationsaufnahmeraten sind hoch. Die respiratorische Insuffizienz bedarf umgehender Diagnostik. Hier zeigt sich eine Überlegenheit der Computertomographie gegenüber der konventionellen Röntgenaufnahme des Thorax. Die Vermeidung einer notwendigen Intubation oder Verzögerung intensivmedizinischer Maßnahmen ist mit hoher Mortalität assoziiert. Fieber ist ein Notfall mit sofortiger Notwendigkeit einer antiinfektiven Therapie. Die Therapie der Sepsis differiert nicht bei neutropenen und nichtneutropenen Patienten. Kardiovaskuläre Erkrankungen sind, teils therapieassoziiert, einer der häufigsten Gründe für Langzeitmorbidität und -mortalität bei Krebspatienten. Immunvermittelte Komplikationen treten zunehmend und teils vital bedrohlich auf, können aber leicht verkannt werden. Spezifische Notfälle, wie Leukostase, Tumorlyse oder Hyperkalzämie, sind eher selten in der Notaufnahme und bedürfen einer interdisziplinären Behandlung. Aufgrund steigender Patientenzahlen ist von einer Zunahme der notfallmedizinischen Behandlungen auszugehen. Die Kenntnis therapieassoziierter Komplikationen ist für Notfallmediziner von zunehmender Bedeutung. Die Vermeidung aggressiver Behandlungsmaßnahmen am Lebensende sollte angestrebt werden.

OBJECTIVE: During therapeutic intervention for adult T-cell leukemia-lymphoma (ATLL), transient red blood cell (RBC) deformations and rapid anemia progression are often observed. These RBC responses are characteristically observed during the treatment of ATLL, and we examined the details and significance of these RBC responses.
METHODS: Seventeen patients with ATLL were enrolled. Peripheral blood smears and laboratory findings were collected during the first two weeks after treatment intervention. We examined the transition of erythrocyte morphology and the factors associated with the induction of anemia.
RESULTS: RBC abnormalities (i.e., elliptocytes, anisocytosis, and schistocytes) rapidly progressed following therapeutic intervention in five of the six cases for whom evaluable consecutive blood smears were available, with significant improvement evident after two weeks. Changes in RBC morphology were significantly associated with the red cell distribution width (RDW). Laboratory findings from all 17 patients showed various levels of anemia progression. A transient increase in RDW values was observed in 11 cases after therapeutic intervention. The degree of progressive anemia during the two-week period was significantly correlated with increased lactate dehydrogenase and soluble interleukin-2 receptor levels and an increase in RDW (P <0.01).
CONCLUSIONS: In cases of ATLL, transient progression of RBC morphological abnormalities and RDW value were observed early after therapeutic intervention. These RBC responses may be associated with tumor and tissue destruction. RBC morphology or RDW values may provide important information about the tumor dynamics and general condition of the patients.

Purpose: Hyperuricemia is a complication arising from tumor lysis syndrome (TLS). Literature has shown that a single 3 mg dose was just as efficacious as a single 6 mg dose when the uric acid (UA) levels were ≤12 mg/dL. Here, we present a multi-center analysis rasburicase utilization and its effect on healthcare costs. Methods: This is a multi-center, retrospective analysis of adult cancer patients who were admitted to Methodist Le Bonheur Healthcare hospitals and received rasburicase from February 2020 to February 2021. The primary endpoint was to test whether rasburicase 3 mg had similar rates of uric acid normalization (defined as uric acid ≤7.5 mg/dL) within 24 h as a dose of 6 mg. Results: Seventy-nine patients were included in the study. While the baseline uric acid was lower in the 3 mg arm compared to the 6 mg arms, there was no difference in the uric acid normalization at 24 h between the 3 mg arm (95%) and 6 mg arm (82%) (p = 0.134). A cost-savings of over $300,000 annually can be achieved with the proposed protocol. Conclusion: A single, fixed rasburicase dose of 3 mg was effective in normalizing uric acid levels within 24 h, and is associated with significant cost-savings.

Tumor lysis syndrome (TLS) is the most common hematologic emergency encountered during the treatment of high-grade malignancies. While it can lead to death, the prognosis is typically excellent if caught early on in the course. Risk stratification prior to treatment initiation is paramount in deciding the utility of prophylaxis and ultimately in reducing morbidity and mortality. The following case describes the development of TLS in a patient categorized as low risk and highlights the need for further elucidation of a unified risk stratification system.

In view of the advancement in the understanding about the most diverse types of cancer and consequently a relentless search for a cure and increased survival rates of cancer patients, finding a therapy that is able to combat the mechanism of aggression of this disease is extremely important. Thus, oncolytic viruses (OVs) have demonstrated great benefits in the treatment of cancer because it mediates antitumor effects in several ways. Viruses can be used to infect cancer cells, especially over normal cells, to present tumor-associated antigens, to activate \"danger signals\" that generate a less immune-tolerant tumor microenvironment, and to serve transduction vehicles for expression of inflammatory and immunomodulatory cytokines. The success of therapies using OVs was initially demonstrated by the use of the genetically modified herpes virus, talimogene laherparepvec, for the treatment of melanoma. At this time, several OVs are being studied as a potential treatment for cancer in clinical trials. However, it is necessary to be aware of the safety and possible adverse effects of this therapy; after all, an effective treatment for cancer should promote regression, attack the tumor, and in the meantime induce minimal systemic repercussions. In this manuscript, we will present a current review of the mechanism of action of OVs, main clinical uses, updates, and future perspectives on this treatment.

BACKGROUND: Venetoclax along with hypomethylating agents (HMAs) is the new standard therapy for older patients with acute myeloid leukemia (AML) not fit for intensive frontline induction chemotherapy. Venetoclax is associated with fatal episodes of tumor lysis syndrome (TLS) in chronic lymphocytic leukemia (CLL), and recommendations are for its initiation for CLL and AML in the inpatient setting with close monitoring. Herein, we evaluated the safety of outpatient venetoclax ramp up when given in addition to HMAs for the treatment of AML.
METHODS: We conducted a retrospective review of patients diagnosed with AML at our institution from 12/1/2016 until 7/1/2020. We identified patients who received HMAs and venetoclax for AML, either as frontline or relapsed/refractory therapy. Records were reviewed for evidence of laboratory or clinical tumor lysis episodes in all patients.
RESULTS: Between 12/1/2016 and 7/1/2020 43, patients at our institution received venetoclax/HMA for the treatment of AML. Thirty-nine patients (91%) had venetoclax initiation and ramp up in the outpatient setting. One episode of laboratory TLS (2.5%) was identified. This patient required admission to the hospital for rasburicase and IV fluids with resolution of the laboratory effects without resultant clinical TLS. There were no episodes of clinical TLS in either group. Thirty-day mortality from venetoclax initiation was 0% in both groups.
CONCLUSIONS: Our experience with HMAs and venetoclax showed that outpatient ramp up of venetoclax is safe with a very low risk of laboratory TLS (2.5%) and no evidence of clinical TLS within our cohort.

Spontaneous tumor lysis syndrome (STLS) is a rare oncologic emergency caused by massive cancer cell lysis or necrosis without a precipitating factor. Although tumor lysis syndrome (TLS) is most commonly associated with hematologic malignancies, a small number of cases in solid tumor malignancies have been reported. We present a case of spontaneous tumor lysis syndrome in a 77-year-old female with a widely metastatic, poorly differentiated adenocarcinoma of unknown origin. She presented in distributive shock, and laboratory testing at admission revealed acute renal failure, high anion gap metabolic acidosis, hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. Rasburicase and continuous renal replacement therapy were initiated, however, her condition deteriorated. Treatment was withdrawn and she died four days after admission.