Synergistic Anti-Angiogenic Effect of Combined VEGFR Kinase Inhibitors, Lenvatinib, and Regorafenib: A Therapeutic Potential for Breast Cancer.

Background: Breast cancer currently affects more than two million women worldwide, and its incidence is steadily increasing. One of the most essential factors of invasion and metastasis of breast cancer cells is angiogenesis and non-angiogenic vascularization. Lenvatinib and Regorafenib share the same anti-angiogenic effect by inhibiting vascular endothelial growth factor receptors (VEGFRs subtypes 1 to 3) and have been approved for treating different types of cancer. Methods: We investigated Lenvatinib and Regorafenib effects on a well-established in-vitro model of breast cancer using MCF-7 (estrogen, progesterone receptor-positive, and HER2-negative), MDA-MB-231 (triple negative), as well as Human Umbilical Vascular Endothelial Cell line (HUVEC) cell lines. We performed the cell viability assay on four groups of cells, which included a control group, a Lenvatinib treated only group, a Regorafenib treated only group, and a group treated with a combination of both drugs at 24, 48, and 72 h. Data were analyzed as means ± standard deviation, and the drug−drug interactions with Compusyn software. Cellular migration assay, tube formation assay, and Western blots were conducted to determine the functional and the protein expression of downstream signals such as Caspase-9, anti-apoptotic Survivin, P-ERK, and total-ERK in the control and treatment groups. Results: MCF-7 cells showed a reduction in cell survival rates with higher dosing and longer incubation periods with each drug and with the combination of drugs. A synergistic interaction was identified (CI < 1) with both drugs on MCF7 at different dose combinations and at a higher dose in MDA-MB-231 cells. Furthermore, there was a marked decrease in the anti-angiogenic effect of both drugs in tube formation assay using MDA-MB-231 cells and survivin protein expression in MCF-7, and those antitumor markers showed a better outcome in drug combination than the use of each drug alone. Conclusion: Our result is the first to report the synergistic anti-angiogenic potential of combination therapy of Lenvatinib and Regorafenib. Therefore, it shows their therapeutic potential in breast cancer, including the aggressive types. Further studies are warranted to confirm and explore this therapeutic approach.

Epidemiological and Clinical Characteristics Associated with COVID-19 Severity Among Hospitalized Patients in the United Arab Emirates: A Retrospective Multicentre Study.

OBJECTIVES: To investigate the clinical and epidemiological factors associated with severe COVID-19 cases in hospitalized patients across two emirates within the United Arab Emirates (UAE). METHODS: A retrospective observational analytical study analysed data from 738 medical records and conducted 573 in-depth interviews with patients hospitalized across multiple healthcare centers in the UAE, between 29 January 2020 and 14 October 2021. Regression analysis predicted risk factors for COVID-19 severity. RESULTS: Main risk factors identified were crowding (aOR 1.919; 95%CI 1.144, 3.221), obesity (aOR 2.383; 95%CI 1.332, 4.263), diabetes (aOR 11.14; 95%CI 2.653-46.797), severe dehydration (aOR 3.219; 95%CI 2.161, 4.795), cough or sore throat (aOR 1.607; 95%CI 1.032, 2.502), shortness of breath (aOR 1.921; 95%CI 1.294, 2.853), increased days from symptom onset to admission (aOR 1.055; 95%CI 1.006, 1.105), elevated ANC (aOR 1.263, 95%CI 1.121, 1.424), and AST/SGOT (aOR 1.055, 95% CI 1.016, 1.095). Protective factors included smoking (aOR 0.367; 95%CI 0.182, 0.740), first dose of COVID-19 vaccination (aOR 0.595; 95%CI 0.377, 0.93), higher oxygen saturation (aOR 0.853; 95%CI: 0.801, 0.907) and elevated ALC (aOR 0.540; 95%CI 0.323, 0.905). CONCLUSION: Identifying risk factors is crucial for high-risk individuals who may require closer monitoring to improve their outcomes. This can provide guidance for surveillance systems and early detection strategies to mitigate the impact of future outbreaks.

Multiple Systemic Arterial Aneurysms in Kawasaki Disease.

Kawasaki disease is a self-limiting systemic vasculitis that can lead to various cardiac complications, including coronary dilatation and aneurysms. However, systemic aneurysms are uncommon and only occur in rare cases. In this instance, we present the case of an eight-week-old infant who presented to the emergency department with fever, loose motion, and neck swelling, ultimately diagnosed with Kawasaki disease accompanied by multiple systemic arterial aneurysms. This case highlights the potential for Kawasaki disease to cause systemic aneurysms and emphasizes the importance of recognizing and monitoring this rare complication in patients diagnosed with Kawasaki disease.

Unusual Presentation of a Hemiplegic Migraine in a Seven-Year-Old Child: A Case Report.

In the pediatric population, headache is a common presenting symptom, and migraine is often the diagnosis. A hemiplegic migraine is characterized by an aura and sudden-onset weakness on one side of the body that usually resolves without causing any permanent neurological damage. In this case, we present a seven-year-old male child with a known case of proximal tubular dysfunction (homozygous mutation in the SLC4A4 gene) who presented to the emergency department with a one-day history of weakness on the right side of his body. A few hours after being discharged from the hospital, he began complaining of a severe headache on the left side, accompanied by photophobia, phonophobia, and high fever. Radiology scans and laboratory workup were unremarkable, and encephalitis was ruled out. He was later diagnosed with hemiplegic migraine based on his history and clinical presentation.

Prolonged Cholestasis Following Acute Hepatitis A Infection: Case Report and a Review of Literature.

Prolonged cholestasis is a rare complication of hepatitis A infection, characterized by a protracted, indolent course with persistent symptoms of pruritus and malabsorption lasting for several months. A 14-year-old girl, previously treated for acute hepatitis A, presented with yellowing of the eyes. An evaluation of her liver function revealed conjugated hyperbilirubinemia, and a liver biopsy confirmed hepatitis with cholestasis. Fortunately, she responded well to conservative treatment and recovered successfully.

Correction: Intestinal Perforation as a Paradoxical Reaction to Tuberculosis.

[This corrects the article DOI: 10.7759/cureus.24077.].

Intestinal Perforation as a Paradoxical Reaction to Tuberculosis.

Paradoxical reactions (PR) to tuberculosis (TB) treatments are characterized by an initial improvement of the clinical symptoms followed by a clinical or radiological deterioration of existing TB lesions or by the development of new lesions. PR in the gastrointestinal system is a rare phenomenon. Moreover, intestinal perforation is an uncommon but potentially fatal complication of intestinal TB. We report the case of a 29-year-old female who presented with fever and abdominal pain that was associated with watery diarrhea. She was diagnosed as a case of intestinal TB. During her stay, she developed intestinal perforation following the initiation of anti-TB treatment. She was eventually managed as a case of intestinal perforation as a PR to TB.