IgA-mediated human autoimmune hemolytic anemia as a result of hemagglutination in the spleen, but independent of complement activation and FcαRI

International audienceAbstract Autoimmune hemolytic anemia (AIHA) due to warm-acting IgA autoantibodies is rare. We explored the pathogenic mechanisms underlying destruction of red blood cells (RBCs) in a patient with severe AIHA mediated exclusively by polymeric immunoglobulin A (pIgA) anti-Band 3 autoantibodies. The follow-up period was 17 months. RBCs were not destroyed by complement activation as no deposition of complement was observed on the patient's RBCs. pIgA eluted from the patient's RBCs did not induce RBC destruction through phagocytosis by monocytes or antibody–dependent cell–mediated cytotoxicity by natural killer cells. Induction of eryptosis (ie, RBC apoptosis) due to direct alteration of the RBC membrane by pIgA autoantibodies was also excluded. By contrast, upon incubation with pIgA-opsonized RBCs, substantial RBC membrane transfers (ie, trogocytosis) to monocytes were observed that might contribute to RBC immune destruction. This effect was poorly inhibited by blockers of Fc receptors, excluding a major contribution of FcαRI to this process. Histologic analysis revealed a massive accumulation of agglutinated RBCs with little sign of erythrophagocytosis in the spleen. These results, together with the efficacy of splenectomy 17 months after AIHA onset, suggest that the trapping and subsequent sequestration of agglutinated RBCs in the spleen are the principal pathogenic mechanisms of pIgA-mediated AIHA

Practice patterns in the management of bacterial keratitis: a five-continent survey

PurposeTo assess the current diagnostic and therapeutic practice patterns in early management of bacterial keratitis over five continents.MethodsBetween March and August 2019, we distributed an online survey including two clinical scenarios of bacterial keratitis, namely, a mild case and severe case, to 2936 ophthalmologists from 144 countries around the world. The survey consisted of 29 questions. We performed descriptive statistics and a comparative analysis of the answers according to the participants' continent of practice, practice setting, seniority, and subspecialty.ResultsWe received 237 surveys from 54 countries (8% response rate). The proportion of respondents performing microbiological investigations was higher in North America, Asia, Europe, and Oceania than Africa and South America (p < 0.05). This ratio was also higher among ocular surface specialists than for other ophthalmologists (p < 0.001). For mild cases, fluoroquinolone monotherapy and a combination of two or more antibiotics were prescribed by 46% and 41% respondents, respectively. For severe cases, fluoroquinolone monotherapy and a combination of antibiotics were prescribed by 20% and 78% respondents, respectively. Fluoroquinolone monotherapy was the most commonly prescribed treatment in South America, Africa, and Oceania. A combination of two antibiotics was preferentially prescribed in the rest of the world. Topical steroids were prescribed in both circumstances, respectively, in 72% and 75% of cases.ConclusionOur results highlight essential geographical disparities in the current management of bacterial keratitis over five continents

Sciatica in the female patient: anatomical considerations, aetiology and review of the literature

The principal author was confronted few years ago with the case of a 38-year-old woman with a 5-month history of ill-defined L5 sciatic pain that was referred to an orthopaedic department for investigation and eventual surgical treatment for what was suspected to be herniated disc-related sciatica. Removal of her enlarged uterus found unexpectedly close to the sacroiliac joint upon lumbar MRI abolished her symptoms. Review of the literature showed that the lumbosacral trunk is vulnerable to pressure from any abdominal mass originating from the uterus and the ovaries. Physiological processes in the female patient and gynaecological diseases may be the source of sciatica, often not readily searched for, leading to fruitless investigations and surgical treatments. The aim of the paper is to highlight gynaecological and obstetrical causes of sciatica and sciatica-like symptoms. To prevent unproductive expenses and morbidity, a thorough gynaecological examination should be done even though neurological examination may be suggestive of a herniated intervertebral disc, and the cyclic pattern of pain related to menses should be routinely asked for

Effect of Alirocumab on Mortality After Acute Coronary Syndromes An Analysis of the ODYSSEY OUTCOMES Randomized Clinical Trial

10.1161/CIRCULATIONAHA.118.038840CIRCULATION1402103-11