No abstract

Ferroptosis, a term first proposed in 2012, is iron-dependent, non-apoptotic regulatory cell death induced by erastin. Ferroptosis was originally discovered during synthetic lethal screening for drugs sensitive to RAS mutant cells, and is closely related to synthetic lethality. Ferroptosis sensitizes cancer stem cells and tumors that undergo epithelial−mesenchymal transition and are resistant to anticancer drugs or targeted therapy. Therefore, ferroptosis-inducing molecules are attractive new research targets. In contrast, synthetic lethal strategies approach mechanisms and genetic abnormalities that cannot be directly targeted by conventional therapeutic strategies, such as RAS mutations, hypoxia, and abnormalities in the metabolic environment. They also target the environment and conditions specific to malignant cells, have a low toxicity to normal cells, and can be used in combination with known drugs to produce new ones. However, the concept of synthetic lethality has not been widely adopted with ferroptosis. In this review, we surveyed the literature on ferroptosis-related factors and synthetic lethality to examine the potential therapeutic targets in ferroptosis-related molecules, focusing on factors related to synthetic lethality, discovery methods, clinical application stages, and issues in drug discovery.

Background Splenic rupture by diffuse large B‐cell lymphoma (DLBCL), which usually progresses insidiously, is extremely rare. Case Presentation A 60‐year‐old man presented with paralysis in his lower left extremity. A magnetic resonance imaging suggested transverse myelitis. No lymphadenopathy or organomegaly was noted. Two months after remission, he was referred to the emergency department complaining of presyncope. He was in preshock due to splenic rupture, and underwent laparotomy after attempts of transcatheter arterial embolization. Splenomegaly, hepatomegaly, and disseminated enlarged lymph nodes were observed. Histological examinations of the resected spleen showed DLBCL. He died of multiple organ failure associated with intractable bleeding. His autopsy revealed diffuse systemic invasions of lymphoma cells except for the brain and spinal cord. Microscopically, the spinal cord showed macular incomplete necrosis and histiocytic infiltration, suggestive of hemophagocytic syndrome. Conclusion The progression of DLBCL in our case is drastically rapid. Undiagnosed transverse myelitis preceded the onset.

Background As messenger RNA (mRNA)-based vaccines for coronavirus disease 2019 (COVID-19) have been administered to millions of individuals worldwide, cases of de novo and relapsing glomerulonephritis after mRNA COVID-19 vaccination are increasing in the literature. While most previous publications reported glomerulonephritis after the first or second dose of an mRNA vaccine, few reports of glomerulonephritis occurring after the third dose of an mRNA vaccine currently exist. Case presentation We report a case of rapidly progressive glomerulonephritis in a patient following the third dose of an mRNA COVID-19 vaccine. A 77-year-old Japanese man with a history of hypertension and atrial fibrillation was referred to our hospital for evaluation of anorexia, pruritus, and lower extremity edema. One year before referral, he received two mRNA vaccines (BNT162b2) for COVID-19. Three months before the visit, he received a third mRNA vaccine (mRNA-1273) for COVID-19. On admission, the patient presented severe renal failure with a serum creatinine level of 16.29 mg/dL, which had increased from 1.67 mg/dL one month earlier, prompting us to initiate hemodialysis. Urinalysis showed nephrotic-range proteinuria and hematuria. Renal biopsy revealed mild mesangial proliferation and expansion, a lobular appearance, and double contours of the glomerular basement membrane. Renal tubules had severe atrophy. Immunofluorescence microscopy showed strong mesangial staining for IgA, IgM, and C3c. Electron microscopy exhibited mesangial and subendothelial electron-dense deposits, leading to a diagnosis of IgA nephropathy with membranoproliferative glomerulonephritis-like changes. The kidney function remained unchanged after steroid therapy. Conclusions Although the link between renal lesions and mRNA vaccines remains unclear, a robust immune response induced by mRNA vaccines may play a role in the pathogenesis of glomerulonephritis. Further studies of the immunological effects of mRNA vaccines on the kidney are warranted.

We encountered a 60-year-old man who had been diagnosed with heart failure of valvular disease and infective endocarditis; he was being treated with intravenous antibiotics and diuretics. On the 12th hospital day, he suddenly lost consciousness; computed tomography showed a right-sided huge subdural hematoma (SDH) with brain herniation. He died after invasive care was discontinued. A massive SDH was noted at autopsy, and microimaging demonstrated ruptured infective arteritis, without aneurysm, on the surface of the culprit lobe. Acute SDH usually occurs after head trauma, but an area of nonsaccular aneurysmal arteritis can also result in acute SDH.