Optimization of risk stratification for anticoagulation-associated intracerebral hemorrhage: net risk estimation

Journal of Neurology - Every anticoagulation decision has in inherent risk of hemorrhage; intracerebral hemorrhage (ICH) is the most devastating hemorrhagic complication. We examined whether...     

ACR Appropriateness Criteria® conservative surgery and radiation--stage I and II breast carcinoma: expert panel on radiation oncology: breast

Breast conservation is a safe and effective alternative to mastectomy for the majority of women with early-stage breast cancer. Adjuvant radiation therapy lowers the risk of recurrence within the breast and also confers a survival benefit. Although acute side effects of radiation therapy are generally well tolerated; efforts are ongoing to minimize the long-term side effects of radiation, most prominently atherosclerotic heart disease. Efforts to minimize radiation therapy are also underway. They include omitting treatment altogether in the elderly and using accelerated, hypofractionated whole-breast irradiation, and accelerated partial-breast irradiation. Several randomized studies are ongoing to determine the efficacy, safety, and appropriate patients for these shorter treatments.     

All India Ophthalmological Society (AIOS) Task Force guidelines to prevent intraocular infections and cluster outbreaks after cataract surgery

Infectious endophthalmitis is a serious and vision-threatening complication of commonly performed intraocular surgeries such as cataract surgery. The occurrence of endophthalmitis can result in severe damage to the uveal and other ocular tissues even among patients undergoing an uncomplicated surgical procedure. If the infections result from common factors such as surgical supplies, operative or operation theater-related risks, there can be a cluster outbreak of toxic anterior segment syndrome (TASS) or infectious endophthalmitis, leading to several patients having an undesirable outcome. Since prevention of intraocular infections is of paramount importance to ophthalmic surgeons, the All India Ophthalmological Society (AIOS) has taken the lead in the formation of a National Task Force to help ophthalmic surgeons apply certain universal precautions in their clinical practice. The Task Force has prepared a handy checklist and evidence-based guidelines to minimize the risk of infectious endophthalmitis following cataract surgery.     

Original research: Nationwide analysis of incidence and predictors of 30-day readmissions in patients with decompensated cirrhosis

Background and objectiveCirrhosis is the number one cause of non-cancer deaths among gastrointestinal diseases and is responsible for significant morbidity and healthcare utilisation. The objectives were to measure the 30-day readmissions rate following index hospitalisation, to determine the predictors of readmission, and to estimate the cost of 30-day readmission in patients with decompensated cirrhosis.MethodsWe performed a retrospective cohort study of patients with decompensated cirrhosis using 2014 Nationwide Readmission Database from January to November. Decompensated cirrhosis was identified based on the presence of at least one of the following: ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis and hepatorenal syndrome. We excluded patients less than 18 years of age, pregnant patients, patients with missing length of stay data, and those who died during the index admission.ResultsAmong 57 305 unique patients with decompensated cirrhosis, the 30-day readmission rate was 23.2%. The top three predictors of 30-day readmission were leaving against medical advice (AMA), ascites and acute kidney injury, which increased the risk of readmission by 47%, 22% and 20%, respectively. Index admission for variceal bleeding was associated with a lower 30-day readmission rate by 18%. The estimated total cost associated with 30-day readmission in our study population was US$234.4 million.ConclusionIn a nationwide population study, decompensated cirrhosis is associated with a 30-day readmission rate of 23%. Leaving AMA, ascites and acute kidney injury are positively associated with readmission. Targeted interventions and quality improvement efforts should be directed toward these potential risk factors to reduce readmissions.     

Deposition of onco-histone H3.3-G34W leads to DNA repair deficiency and activates cGAS/STING-mediated immune responses

Mutations in histone H3.3-encoding genes causing mutant histone tails are associated with specific cancers such as pediatric glioblastomas (H3.3-G34R/V) and giant cell tumor of the bone (H3.3-G34W). The mechanisms by which these mutations promote malignancy are not completely understood. Here we show that cells expressing H3.3-G34W exhibit DNA double-strand breaks (DSBs) repair defects and increased cellular sensitivity to ionizing radiation (IR). Mechanistically, H3.3-G34W can be deposited to damaged chromatin, but in contrast to wild-type H3.3, does not interact with non-homologous end-joining (NHEJ) key effectors KU70/80 and XRCC4 leading to NHEJ deficiency. Together with defective cell cycle checkpoints reported previously, this DNA repair deficiency in H3.3-G34W cells led to accumulation of micronuclei and cytosolic DNA following IR, which subsequently led to activation of the cyclic GMP-AMP synthase/stimulator of interferon genes (cGAS/STING) pathway, thereby inducing release of immune-stimulatory cytokines. These findings suggest a potential for radiotherapy for tumors expressing H3.3-G34W, which can be further improved by combination with STING agonists to induce immune-mediated therapeutic efficacy.