Clinical Practice Guidelines in the Management of Breakthrough Cancer Pain: A Systematic Review using the Appraisal of Guidelines for Research and Evaluation (AGREE II) Instrument.

BACKGROUND: Several clinical practice guidelines (CPGs), consensus statements, and recommendations currently exist for the diagnosis and management of breakthrough cancer pain (BTcP). These documents have considerable variability amongst them, and to date, their quality and methodologic rigor have not been appraised. AIM: We aim to identify and perform a quality appraisal of CPGs for the diagnosis and management of BTcP using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. METHODS: A comprehensive literature search was performed in MEDLINE (via PubMed), EMBASE, and SCOPUS databases up until January 1, 2021. Four reviewers independently evaluated each guideline using the AGREE II instrument. Scaled domain scores were generated and the threshold used for satisfactory quality was >60%. Additionally, intraclass correlation coefficients (ICC) were calculated to determine level of agreement between reviewers. RESULTS: Eleven guidelines were selected for final evaluation based on inclusion/exclusion criteria. Only one guideline was classified of "average" quality while the rest were classified as "low" quality. The "Editorial Independence" (70.46 ± 35.7) and "Scope and Purpose" (64.78 ± 12.5) domains received the highest mean scores, while the "Applicability" (32.58 ± 13.5) and "Rigor of Development" (35.04 ± 9.0) domains received the lowest mean scores. ICC statistical analysis showed high magnitude of agreement between reviewers with a range of (0.790-0.988). CONCLUSIONS: Reflecting upon our quality appraisal, it is evident that the quality and methodologic rigor of BTcP guidelines can be improved upon in the future. Our findings also elucidate the existing variability/discrepancies among guidelines in diagnostic criteria and management of BTcP.

Review of Current and Future Medical Treatments in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is a complex cancer requiring a multidisciplinary approach. For patients with locally or regionally advanced disease, surgery and/or radiation are the cornerstones of definitive treatment. Medical therapy plays an important adjunct role in this setting, typically consisting of a platinum-based regimen given as induction, concurrent, or adjuvant treatment. While relapsed/metastatic HNSCC has historically been a difficult-to-treat disease with poor outcomes, options have considerably improved with the incorporation of biologics and immune checkpoint inhibitors. Clinical trials are ongoing to investigate novel approaches, including new and combination immunotherapies, targeted therapies, therapeutic vaccines, antibody-drug conjugates, and cellular therapies. The results thus far have been mixed, highlighting the knowledge gaps that continue to challenge the medical oncologist treating HNSCC. Here, we present the most updated and broad review of the current treatment landscape in both locoregional and metastatic HNSCC and discuss the expansive future medical therapies under investigation.

Evidence showing lipotoxicity worsens outcomes in covid-19 patients and insights about the underlying mechanisms.

We compared three hospitalized patient cohorts and conducted mechanistic studies to determine if lipotoxicity worsens COVID-19. Cohort-1 (n = 30) compared COVID-19 patients dismissed home to those requiring intensive-care unit (ICU) transfer. Cohort-2 (n = 116) compared critically ill ICU patients with and without COVID-19. Cohort-3 (n = 3969) studied hypoalbuminemia and hypocalcemia's impact on COVID-19 mortality. Patients requiring ICU transfer had higher serum albumin unbound linoleic acid (LA). Unbound fatty acids and LA were elevated in ICU transfers, COVID-19 ICU patients and ICU non-survivors. COVID-19 ICU patients (cohort-2) had greater serum lipase, damage-associated molecular patterns (DAMPs), cytokines, hypocalcemia, hypoalbuminemia, organ failure and thrombotic events. Hypocalcemia and hypoalbuminemia independently associated with COVID-19 mortality in cohort-3. Experimentally, LA reacted with albumin, calcium and induced hypocalcemia, hypoalbuminemia in mice. Endothelial cells took up unbound LA, which depolarized their mitochondria. In mice, unbound LA increased DAMPs, cytokines, causing endothelial injury, organ failure and thrombosis. Therefore, excessive unbound LA in the circulation may worsen COVID-19 outcomes.