Early Administration of Intravenous Hydration and Opioid Analgesics Is Correlated with Decreased Admission Rates during Vaso-Occlusive Episodes in Sickle Cell Disease.

Background: Painful vaso-occlusive episodes (VOEs) are the hallmark of sickle cell disease (SCD) and account for frequent visits to the emergency department (ED) or urgent care (UC). Currently, the early administration of analgesics is recommended as initial management; however, there is a need for further understanding of the effect of prompt analgesics and hydration during VOEs. The objective of this study is to analyze the factors associated with the rate of hospital admission in the setting of time to intravenous (IV) analgesics and hydration. Method: This retrospective single-institution study reviewed adult and pediatric patients with SCD who presented with VOEs from January 2018 to August 2023. Results: Of 303 patient encounters, the rates of admission for the overall group, the subgroup which received IV hydration within 60 min of arrival, and the subgroup which received both IV analgesics and hydration within 60 min were 51.8%, 25.6% (RR = 0.46), and 18.2% (RR = 0.33), respectively. Further, factors such as gender and the use of hydroxyurea were found to be significantly associated with the rate of admission. Conclusions: This signifies the importance of standardizing the management of VOEs through the timely administration of IV analgesics and hydration in both adult and pediatric ED/UC.

Comprehensive Review: Unveiling the Pro-Oncogenic Roles of IL-1ß and PD-1/PD-L1 in NSCLC Development and Targeting Their Pathways for Clinical Management.

In the past decade, targeted therapies for solid tumors, including non-small cell lung cancer (NSCLC), have advanced significantly, offering tailored treatment options for patients. However, individuals without targetable mutations pose a clinical challenge, as they may not respond to standard treatments like immune-checkpoint inhibitors (ICIs) and novel targeted therapies. While the mechanism of action of ICIs seems promising, the lack of a robust response limits their widespread use. Although the expression levels of programmed death ligand 1 (PD-L1) on tumor cells are used to predict ICI response, identifying new biomarkers, particularly those associated with the tumor microenvironment (TME), is crucial to address this unmet need. Recently, inflammatory cytokines such as interleukin-1 beta (IL-1ß) have emerged as a key area of focus and hold significant potential implications for future clinical practice. Combinatorial approaches of IL-1ß inhibitors and ICIs may provide a potential therapeutic modality for NSCLC patients without targetable mutations. Recent advancements in our understanding of the intricate relationship between inflammation and oncogenesis, particularly involving the IL-1ß/PD-1/PD-L1 pathway, have shed light on their application in lung cancer development and clinical outcomes of patients. Targeting these pathways in cancers like NSCLC holds immense potential to revolutionize cancer treatment, particularly for patients lacking targetable genetic mutations. However, despite these promising prospects, there remain certain aspects of this pathway that require further investigation, particularly regarding treatment resistance. Therefore, the objective of this review is to delve into the role of IL-1ß in NSCLC, its participation in inflammatory pathways, and its intricate crosstalk with the PD-1/PD-L1 pathway. Additionally, we aim to explore the potential of IL-1ß as a therapeutic target for NSCLC treatment.

Targeting the Tumor Microenvironment in Acute Myeloid Leukemia: The Future of Immunotherapy and Natural Products.

The tumor microenvironment (TME) plays an essential role in the development, proliferation, and survival of leukemic blasts in acute myeloid leukemia (AML). Within the bone marrow and peripheral blood, various phenotypically and functionally altered cells in the TME provide critical signals to suppress the anti-tumor immune response, allowing tumor cells to evade elimination. Thus, unraveling the complex interplay between AML and its microenvironment may have important clinical implications and are essential to directing the development of novel targeted therapies. This review summarizes recent advancements in our understanding of the AML TME and its ramifications on current immunotherapeutic strategies. We further review the role of natural products in modulating the TME to enhance response to immunotherapy.

A rare case of extremely delayed osseous metastasis of pineoblastoma.

Pineoblastoma is a rare, primitive, and malignant tumor arising from the parenchyma of the pineal gland. It typically metastasizes along the cerebral neural axis, with rare extraneural metastasis and even more rare intraosseous extraneural metastasis. A patient with pineoblastoma, initially treated with chemotherapy, presented 10 years after initial diagnosis with multiple osseous metastases including his pelvis, femur, and vertebrae, and is currently undergoing chemotherapy.

A case report of imiquimod topical therapy as treatment for cutaneous metastasis of breast cancer.

Cutaneous metastasis of breast cancer carries a poor prognosis, invokes a poor quality of life, and increases mortality by raising one's risk of bleeding and infection. Currently, options for treatment are systemic chemotherapy, surgical resection and radiation. These treatments are invasive and can have toxic side effects. A 50-year-old African-American woman with stage IV breast cancer with cutaneous metastasis to the left anterior chest and left supraclavicular area was successfully treated with topical imiquimod. She experienced improvement in appearance and symptoms within several months of starting treatment, resulting in near resolution of her cutaneous metastasis. Imiquimod is currently approved for several cutaneous conditions and has the potential to treat cutaneous metastasis of breast cancer.

Anthracycline-induced cardiotoxicity: A case report and review of literature.

BACKGROUND: Doxorubicin and other anthracycline derivatives inhibit topoisomerase II and is an important class of cytotoxic chemotherapy in cancer treatment. The use of anthracycline is limited by dose-dependent cardiotoxicity, which may manifest initially as asymptomatic cardiac dysfunction with subsequent progression to congestive heart failure. Despite baseline assessment and periodic monitoring of cardiac function for patients receiving anthracycline agents, there are unmet needs in prediction and prevention of anthracycline-induced cardiotoxicity (AIC). CASE SUMMARY: A 35-year-old African American female was found to have a 9-cm high-grade osteosarcoma of right femur and normal baseline cardiac function with left ventricular ejection fraction of approximately 60%-70% determined by transthoracic and dobutamine stress echocardiogram. She underwent perioperative doxorubicin and cisplatin chemotherapy with 3 cycles before surgery and 3 cycles after surgery, and received a total of 450 mg/m2 doxorubicin at the end of her treatment course. She was evaluated regularly during chemotherapy without any cardiac or respiratory symptoms. Approximately two months after her last chemotherapy, the patient presented to the emergency department with dyspnea for one week and was intubated for acute hypoxic respiratory failure. Echocardiogram showed an ejection fraction of 5%-10% with severe biventricular failure. Despite attempts to optimize cardiac function, the patient's hemodynamic status continued to decline, and resuscitation was not successful on the seventh day of hospitalization. The autopsy showed no evidence of osteosarcoma, and the likely cause of death was cardiac failure with the evidence of pulmonary congestion, liver congestion, and multiple body cavity effusions. CONCLUSION: We present a case of 35-year-old African American female developing cardiogenic shock shortly after receiving a cumulative dose of 450 mg/m2 doxorubicin over 9 mo. Cardiac monitoring and management of patients receiving anthracycline chemotherapy have been an area of intense research since introduction of these agents in clinical practice. We have reviewed literature and recent advances in the prediction and prevention of AIC. Although risk factors currently identified can help stratify patients who need closer monitoring, there are limitations to our current understanding and further research is needed in this field.

Real world outcomes of combination and timing of immunotherapy with radiotherapy for melanoma with brain metastases.

INTRODUCTION: Immunotherapy (IT) and radiotherapy (RT) have improved overall survival in patients with melanoma with brain metastasis (MBM). We examined the real-world survival impact of IT and RT combination and timing strategies. MATERIALS AND METHODS: From the facility-based National Cancer Database (NCDB) data set, 3008 cases of MBM were identified between 2011 and 2015. Six treatment cohorts were identified: stereotactic radiosurgery (SRS) + IT, SRS alone, whole brain radiotherapy (WBRT) + IT, WBRT alone, IT alone, and none. Concurrent therapy was defined as IT given within 28 days before or after RT; nonconcurrent defined as IT administered within 28-90 days of RT. The co-primary outcomes were propensity score-adjusted overall survival by treatment regimen and overall survival by RT and IT timing. RESULTS: Median overall survival (mOS) was performed for each treatment category; SRS +IT 15.77 m; (95%CI 12.13-21.29), SRS alone (9.33 m; 95%CI: 8.0-11.3), IT alone (7.29 m; 95%CI: 5.35-12.91), WBRT +IT (4.89 m; 95%CI: 3.65-5.92), No RT or IT (3.29 m; 95%CI: 2.96-3.75), and WBRT alone (3.12 m; 95%CI 2.79-3.52). By propensity score matching, mOS for SRS +IT (15.5 m; 95%CI: 11.5-20.2) was greater than SRS alone (10.1 m; 95%CI: 8.4-11.8) (p = 0.010), and median survival for WBRT +IT (4.6 m; 95%CI: 3.4-5.6) was greater than WBRT alone (2.9 m; 95%CI: 2.5-3.5) (p < 0.001). In the SRS +IT group, 24-month landmark survival was 47% (95%CI; 42-52) for concurrent versus 37% (95%CI; 30-44) for nonconcurrent (p = 0.40). CONCLUSION: Those who received IT in addition to WBRT and SRS experienced longer survival compared to RT modalities alone, while those receiving concurrent SRS and IT trended toward improved survival versus nonconcurrent therapy.

Primary chemoradiation with cisplatin versus cetuximab for locally advanced head and neck cancer: a retrospective cohort study.

OBJECTIVE: To explore the efficacy of primary chemoradiation with cisplatin versus cetuximab with respect to HPV/p16 and smoking statuses. METHODS: We retrospectively reviewed patients from our center with locally advanced non-nasopharyngeal head and neck squamous cell carcinoma (HNSCC) who received primary chemoradiation with cisplatin or cetuximab between 2006 and 2018. RESULTS: The median OS for cisplatin (n = 66) was not reached versus 132 months when treated with cetuximab (n = 55) (p = 0.03). For HPV/p16-positive patients, we found the median OS for cisplatin (n = 34) was not reached versus 60 months with cetuximab (n = 21) (p = 0.036). In the smoking group, the median OS was not reached in the cisplatin group (n = 44) versus 60 months when treated with cetuximab (n = 32) (p = 0.03). CONCLUSION: HPV/p16-positive and smoking cohorts treated with cisplatin-based chemoradiotherapy had a significantly better OS versus cetuximab.