Real-world approaches to outpatient treatment of status migrainosus: A survey study.

OBJECTIVES: Identify how the American Headache Society (AHS) membership manages status migrainosus (SM) among outpatients. BACKGROUND: SM is defined as a debilitating migraine attack lasting more than 72 h. There is no standard of care for SM, including whether a 72-h duration is required before the attack can be treated as SM. METHODS: The Refractory Headache Special Interest Group from AHS developed a four-question survey distributed to AHS members enquiring (1) whether they treat severe refractory migraine attacks the same as SM regardless of duration, (2) what their first step in SM management is, (3) what the top three medications they use for SM are, and (4) whether they are United Council for Neurologic Subspecialties (UCNS) certified. The survey was conducted in January 2022. Descriptive statistical analyses were performed. RESULTS: Responses were received from 196 of 1859 (10.5%) AHS members; 64.3% were UCNS certified in headache management. Respondents treated 69.4% (136/196) of patients with a severe refractory migraine attack as SM before the 72-h period had elapsed. Most (76.0%, 149/196) chose "treat remotely using outpatient medications at home" as the first step, 11.2% (22/196) preferred procedures, 6.1% (12/196) favored an infusion center, 6.1% (12/196) sent patients to the emergency department (ED) or urgent care, and 0.5% (1/196) preferred direct hospital admission. The top five preferred medications were as follows: (1) corticosteroids (71.4%, 140/196), (2) nonsteroidal anti-inflammatory drugs (NSAIDs) (50.1%, 99/196), (3) neuroleptics (46.9%, 92/196), (4) triptans (30.6%, 60/196), and (5) dihydroergotamine (DHE) (21.4%, 42/196). CONCLUSIONS: Healthcare professionals with expertise in headache medicine typically treated severe migraine attacks early and did not wait 72 h to fulfill the diagnostic criteria for SM. Outpatient management with one or more medications for home use was preferred by most respondents; few opted for ED referrals. Finally, corticosteroids, NSAIDs, neuroleptics, triptans, and DHE were the top five preferred treatments for home SM management.

The role of urgent care centers in headache management: a quality improvement project.

BACKGROUND: Patients with headache often seek urgent medical care to treat pain and associated symptoms that do not respond to therapeutic options at home. Urgent Cares (UCs) may be suitable for the evaluation and treatment of such patients but there is little data on how headache is evaluated in UC settings and what types of treatments are available. We conducted a study to evaluate the types of care available for patients with headache presenting to UCs. DESIGN: Cross-Sectional. METHODS: Headache specialists across the United States contacted UCs to collect data on a questionnaire. Questions asked about UC staffing (e.g. number and backgrounds of staff, hours of operation), average length of UC visits for headache, treatments and tests available for patients presenting with headache, and disposition including to the ED. RESULTS: Data from 10 UC programs comprised of 61 individual UC sites revealed: The vast majority (8/10; 80%) had diagnostic testing onsite for headache evaluation. A small majority (6/10; 60%) had the American Headache Society recommended intravenous medications for acute migraine available. Half (5/10) had a headache protocol in place. The majority (6/10; 60%) had no follow up policy after UC discharge. CONCLUSIONS: UCs have the potential to provide expedited care for patients presenting for evaluation and treatment of headache. However, considerable variability exists amongst UCs in their abilities to manage headaches. This study reveals many opportunities for future research including the development of protocols and professional partnerships to help guide the evaluation, triage, and treatment of patients with headache in UC settings.

The role of cancer stem cells and miRNAs in defining the complexities of brain metastasis.

Researchers and clinicians have been challenged with the development of therapies for the treatment of cancer patients whose tumors metastasized to the brain. Among the most lethal weapons known today, current management of brain metastases involves multiple therapeutic modalities that provide little, if any, for improving the quality of life and overall survival. Recently the role of cancer stem cells (CSCs) in the development of cancer has been studied extensively, and thus its role in the prognosis, diagnosis, and treatment is now being investigated even in the realm of brain metastasis (BM). Recognizing the molecular make-up of CSCs as well as understanding the role of these cells in resistance to treatment modalities is expected to benefit cancer patients. Additionally, past decade has witnessed an increase in awareness and understanding of the role of microRNAs (miRNAs) in various cancer types, and the deregulation miRNAs are critically important for the regulation of genes during the development and progression of human malignancies. The role miRNAs in BM is being investigated, and has also shown tremendous promise for future research. In this review, we discuss the problem and lethality of brain metastases and the current state of management, and further provide insight into novel avenues that are worth considering including the biological complexities of CSCs and miRNAs for designing novel therapies.

3,3'-Diindolylmethane enhances taxotere-induced growth inhibition of breast cancer cells through downregulation of FoxM1.

Emerging evidence suggests that the transcription factor Forkhead Box M1 (FoxM1) is associated with aggressive human carcinomas, including breast cancer. Because elevated expression of FoxM1 has been observed in human breast cancers, FoxM1 has attracted much attention in recent years as a potential target for the prevention and/or therapeutic intervention in breast cancer. However, no information is currently available regarding how downregulation of FoxM1 could be achieved for breast cancer prevention and therapy. Here, we report for the first time that 3,3'-diindolylmethane (DIM), a nontoxic dietary chemopreventive agent could effectively downregulate FoxM1 in various breast cancer cell lines. Using gene transfection, real-time reverse transcription-PCR, Western blotting, invasion and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, we found that DIM could enhance Taxotere-induced growth inhibition of breast cancer cells, and decreased invasive capacity of breast cancer cells was observed after either treatment alone or the combination. These effects were associated with downregulation of FoxM1. We also found that knock down of FoxM1 expression by small interfering RNA (siRNA) transfection increased DIM-induced cell growth inhibition, whereas over-expression of FoxM1 by cDNA transfection attenuated DIM-induced cell growth inhibition, suggesting the mechanistic role of FoxM1. Most importantly, the combination treatment significantly inhibited tumor growth in severe combined immunodeficiency (SCID) mice, and the results were correlated with the downregulation of FoxM1 in tumor remnants. We conclude that inactivation of FoxM1 and its target genes by DIM could enhance the therapeutic efficacy of Taxotere in breast cancer, which could be a useful strategy for the prevention and/or treatment of breast cancer.

Exploitation of protein kinase C: a useful target for cancer therapy.

Protein kinase C is a family of serine/threonine kinases. The PKC family is made up of at least 12 isozymes, which have a role in cell proliferation, differentiation, angiogenesis, and apoptosis. Activation of PKC isozyme is dependent on tyrosine-kinase receptors and G-protein-coupled receptors. PKC isozymes regulate multiple signaling pathways including PI3-K/Akt, MAPK, and GSK-3beta. PKC isozymes have variable roles in tumor biology which in part depend on the cell type and intracellular localization. PKC isozymes are commonly dysregulated in the cancer of the prostate, breast, colon, pancreatic, liver, and kidney. Currently, several classes of PKC inhibitors are being evaluated in clinical trials and several challenges in targeting PKC isozymes have been recently identified. In conclusion, PKC remains a promising target for cancer prevention and therapy.

A novel copper complex of 3-benzoyl-alpha methyl benzene acetic acid with antitumor activity mediated via cyclooxygenase pathway.

Pancreatic cancer (PC) is characterized as one of the deadliest malignancies and its treatment is a great challenge to clinical oncologists. Expression of COX-2 is detectable in 75% of PCs among which 50% showed overexpression, suggesting the importance of COX-2 enzyme and its metabolic product prostaglandin E2 (PGE(2)) in PC. Here the authors report the synthesis and biological activity of a novel COX-2 inhibitor, FPA-306, and its effects on PC cells with different levels of COX-2 expression. Using MTT assay, the authors found a significant growth inhibition of BxPC-3 cells treated by FPA-306 with an IC(50) of 10 micromol/L, which was lower than that of ketoprofen (IC(50) = 35.4 micromol/L) and celecoxib (IC(50) > 100 micromol/L). There was no such effect found in MIAPaCa cell line, which does not express COX-2. The authors also found dose dependent reduction in cell survival and induction of apoptosis by FPA-306 treatment in BxPC-3 cells but not in MIAPaCa cells. These results were correlated with apoptosis data and secreted PGE(2) levels. The molecular modeling of FPA-306 in the COX-2 active site showed that FPA-306 is potentially able to inhibit the activity of enzyme by blocking the active site, thereby resulting in decreased PGE(2) production. The authors also found a significant reduction of COX-2 at the mRNA and protein levels together with downregulation of NF-kappaB DNA binding activity and its downstream genes, Bcl-2 and survivin. These results suggest that FPA-306 is an effective and potent agent in inhibiting the growth of PC cells.