Journal of internal medicine
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Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the enzyme cyclooxygenase (COX), which forms prostaglandins involved in pain and inflammation. COX inhibitors have analgesic and anti-inflammatory effects, but also increase risks for gastrointestinal ulcers, bleeding, and renal and cardiovascular adverse events. Identification of two isoforms of COX, COX-1 and COX-2, led to the development of selective COX-2 inhibitors, which were launched as having fewer gastrointestinal side effects since gastroprotective prostaglandins produced via COX-1 are spared. ⋯ Randomized trials comparing COX-2 inhibitors with NSAIDs have exaggerated their gastrointestinal benefits by using maximal NSAID doses regardless of indication, and/or hidden the cardiovascular risk by comparing with COX-2 selective diclofenac instead of low-dose ibuprofen or naproxen. Observational studies show increased cardiovascular risks within weeks of treatment with COX-2 inhibitors and high doses of NSAIDs other than naproxen, which is the safest alternative. COX inhibitors are symptomatic drugs that should be used intermittently at the lowest effective dosage, especially among individuals with an increased cardiovascular risk.
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Worldwide, nations have struggled during the coronavirus disease 2019 (COVID-19) pandemic. However, Latin America and the Caribbean faced an unmatched catastrophic toll. As of March 2022, the region has reported approximately 15% of cases and 28% of deaths worldwide. ⋯ Moreover, reliance on repurposed and ineffective drugs such as hydroxychloroquine and ivermectin-to treat or prevent COVID-19-was publicised through misinformation and created a false sense of security and poor adherence to social distancing measures. While there were hopes that herd immunity could be achieved after the region's disastrous first peak, the emergence of the Gamma, Lambda, and Mu variants made this unattainable. This review explores how Latin America and the Caribbean fared during the first 2 years of the pandemic, and how, despite all the challenges, the region became a global leader in COVID-19 vaccination, with 63% of its population fully vaccinated.
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DNA methylation is an epigenetic modification that has consistently been shown to be linked with a variety of human traits and diseases. Because DNA methylation is dynamic and potentially reversible in nature and can reflect environmental exposures and predict the onset of diseases, it has piqued interest as a potential disease biomarker. DNA methylation patterns are more stable than transcriptomic or proteomic patterns, and they are relatively easy to measure to track exposure to different environments and risk factors. ⋯ In this review, we will first discuss the advantages and challenges of DNA methylation biomarkers in general. We will then review the current state and future potential of DNA methylation biomarkers in two human traits that show rather consistent alterations in methylome-obesity and smoking. Lastly, we will briefly speculate about the future prospects of DNA methylation biomarkers, and possible ways to achieve them.
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Immunotherapy in cancer takes advantage of the exquisite specificity, potency, and flexibility of the immune system to eliminate alien tumor cells. It involves strategies to activate the entire immune defense, by unlocking mechanisms developed by tumor cells to escape from surrounding immune cells, as well as engineered antibody and cellular therapies. What is important to note is that these are therapeutics with curative potential. ⋯ In this review, we discuss developmental trends of immunotherapy in hematological malignancies, focusing on some of the strategies that we believe will have the most impact on future clinical practice in this field. In particular, we delineate novel developments for therapies that have already been introduced into the clinic, such as immune checkpoint inhibition and chimeric antigen receptor T-cell therapies. Finally, we discuss the therapeutic potential of emerging strategies based on T-cell receptors and adoptive transfer of allogeneic natural killer cells.
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The genetic architecture of cancer has been delineated through advances in high-throughput next-generation sequencing, where the sequential acquisition of recurrent driver mutations initially targeted towards normal cells ultimately leads to malignant transformation. Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are hematologic malignancies frequently initiated by mutations in the normal hematopoietic stem cell compartment leading to the establishment of leukemic stem cells. Although the genetic characterization of MDS and AML has led to identification of new therapeutic targets and development of new promising therapeutic strategies, disease progression, relapse, and treatment-related mortality remain a major challenge in MDS and AML. ⋯ Therefore, targeted surveillance of leukemic stem cells following therapy should, in the future, allow better prediction of relapse and disease progression, but is currently challenged by our restricted ability to distinguish leukemic stem cells from other leukemic cells and residual normal cells. To advance current and new clinical strategies for the treatment of MDS and AML, there is a need to improve our understanding and characterization of MDS and AML stem cells at the cellular, molecular, and genetic levels. Such work has already led to the identification of promising new candidate leukemic stem cell molecular targets that can now be exploited in preclinical and clinical therapeutic strategies, towards more efficient and specific elimination of leukemic stem cells.