#GastricCancer is a common and often lethal cancer that, like cervical and liver cancer, can be attributed in large part to an infectious cause.
Full editorial on gastric cancer risk available here: nej.md/3JQQY4v 1/15
In the case of gastric cancer, the infectious agent is a bacterium, Helicobacter pylori. Until now, hereditary forms of gastric cancer were thought to be limited to a small percentage of CDH1-mutant cases. 2/15
In this week’s issue of NEJM, Usui et al. provide compelling evidence for a substantial contribution from inherited (germline) variants in nine cancer genes to the risk of gastric cancer. Read the study here: nej.md/40Br5MC 3/15
They found that pathogenic variants in genes were much more common among patients with gastric cancer than in the general population, and these variants “collaborated” with H. pylori infection to strongly elevate the risk of gastric cancer. 4/15
These findings imply that the hereditary contribution to the risk of gastric cancer is more important than previously believed and suggests that DNA damage induced by H. pylori, if repaired incorrectly or not at all, is a major driver of gastric carcinogenesis. 5/15
Environmental exposures are believed to drive the vast majority of cases of gastric cancer; in contrast, hereditary germline mutations were previously assumed to account for only 1 to 3% of cases of gastric cancer. 6/15
The concept that gastric cancer largely lacks a hereditary component — and that hereditary cancer syndromes confer a predisposition to breast, ovarian, and colon cancer but not to gastric cancer — is fundamentally challenged by the study by Usui et al. 7/15
The futile attempts of the host to eradicate an H. pylori infection fuel chronic gastric inflammation, which may progress to chronic atrophic gastritis and intestinal metaplasia. 8/15
Although such immunopathologic lesions are well-documented precursor lesions of the “intestinal type” of gastric cancer, H. pylori is also known to have genotoxic activity that is likely to contribute to malignant transformation of gastric epithelial cells. 9/15
The genotoxicity of H. pylori depends in large part on its expression of a functional T4SS and is readily detected in cultured gastric cell lines, organoid cells, and biopsy specimens from patients with H. pylori–induced chronic gastritis. 10/15
H. pylori–induced DNA damage manifests in the form of DNA double-strand breaks that are evident as discontinuities in metaphase chromosomes and through evidence of attempts by the damaged cell to repair its double-strand breaks. 11/15
Two major pathways of H. pylori–induced double-strand breaks have been described; these pathways are complex and likely to be complementary, and they predominantly affect cells during a specific phase of the cell cycle (S phase). 12/15
Although the DNA-damaging activity of H. pylori was first described more than a decade ago, it is only now — thanks to Usui et al. — that we are finally beginning to understand how DNA damage induced by the pathogen promotes malignant transformation. 13/15
It does so in the context of hereditary homologous recombination deficiency. In this respect, it is an example of “multihit” carcinogenesis, in that two or more “hits” are required for cancer to occur. 14/15
Read “A Double Whammy on Gastric Cancer Risk” by Anne Müller, Ph.D., and Jiazhuo He, M.D.: nej.md/3JQQY4v 15/15
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The recent release of ChatGPT and other artificial intelligence tools have put a spotlight on this developing topic. This thread explores the history of AI in medicine, clinical uses of AI and machine learning, and the use of chatbots. Full article: nej.md/3nt4zHH 1/24
As computers and the concept of artificial intelligence (AI) were almost simultaneously developed in the 1940s and 1950s, the field of medicine was quick to see their potential relevance and benefit. 2/24
In 1959, Keeve Brodman and colleagues claimed that “the making of correct diagnostic interpretations of symptoms can be a process in all aspects logical and so completely defined that it can be carried out by a machine.” 3/24
The specialty of #CriticalCare has achieved important advances in survival for many patients with the most complex disorders. Along with these advances, however, there has been an increasing awareness of the complicated and persistent morbidity that follows critical illness. 1/10
Episodes of critical illness result in multidimensional acquired or exacerbated conditions that may persist for years after the critical illness and may not be wholly reversible. Health inequities may worsen these outcomes. 2/10
A continuum of care for patients and families after critical illness, extending from the ICU to community or primary care, must become the standard of care and be developed concurrently with basic science inquiry to elucidate the multiple mechanisms of morbidity. 3/10
Ventricular fibrillation and sudden death triggered by a blunt, nonpenetrating, and often innocent-appearing blow to the chest without damage to the ribs, sternum, or heart (and in the absence of underlying cardiovascular disease) constitute an event known as commotio cordis. 1/9
A March 11, 2010, Review Article in NEJM focuses on the clinical profile, proposed mechanisms, and prevention and treatment of commotio cordis. Read the free article: nej.md/CommotioCordis 2/9
Commotio cordis shows a predilection for children and adolescents. According to the National Commotio Cordis Registry in Minneapolis, 26% of victims were younger than 10 years of age, and only 9% were 25 years of age or older. 3/9