An impaired ability to regulate the activation of microglia by fractalkine (CX3CL1) leads to persistent neuroinflammation and behavioral alterations following lipopolysaccharide (LPS) challenge. While these responses are usually transient, LPS injection caused prolonged depressive-like behavior in fractalkine receptor deficient mice (CX3CR1−/−) that was associated with exaggerated microglial activation and induction of the tryptophan (TRP) degrading enzyme indoleamine 2,3-dioxygenase (IDO). IDO activation and subsequent generation of neuroactive kynurenine metabolites may have a pivotal role in the development of depression. Therefore, the purpose of this study was to determine the extent to which LPS-induced depressive-like behavior in CX3CR1−/− mice was dependent on IDO activation. CX3CR1−/− mice were implanted prior to LPS challenge with a slow release pellet of 1-methyl-tryptophan (1-MT), a competitive inhibitor of IDO. Here we show that the depressive-like behavior evident in CX3CR1−/− mice 72 h after LPS injection was abrogated by inhibition of IDO. LPS also decreased body weight and locomotor activity in CX3CR1−/− mice, but these effects were independent of 1-MT. Consistent with the increased metabolism of TRP by IDO, the ratio of 3-hydroxykynurenine (3-HK) to TRP was increased in the brain 72 h after LPS. Increased serotonin (5-HT) turnover was also evident in the brain. The LPS-associated increases in both 3-HK:TRP and 5-HIAA:5-HT ratios were prevented by the inhibition of IDO. Last, IDO blockade attenuated microglial activation in the prefrontal cortex and hippocampus 72 h after LPS. Collectively these data indicate that LPS-induced IDO activation contributes to persistent microglial activation and depressive-like behavior in CX3CR1−/− mice.

Traumatic brain injury (TBI) is associated with cerebral edema, blood brain barrier breakdown, and neuroinflammation that contribute to the degree of injury severity and functional recovery. Unfortunately, there are no effective proactive treatments for limiting immediate or long-term consequences of TBI. Therefore, the objective of this study was to determine the efficacy of methylene blue (MB), an antioxidant agent, in reducing inflammation and behavioral complications associated with a diffuse brain injury. Here we show that immediate MB infusion (intravenous; 15-30 minutes after TBI) reduced cerebral edema, attenuated microglial activation and reduced neuroinflammation, and improved behavioral recovery after midline fluid percussion injury in mice. Specifically, TBI-associated edema and inflammatory gene expression in the hippocampus were significantly reduced by MB at 1 d post injury. Moreover, MB intervention attenuated TBI-induced inflammatory gene expression (interleukin [IL]-1β, tumor necrosis factor α) in enriched microglia/macrophages 1 d post injury. Cell culture experiments with lipopolysaccharide-activated BV2 microglia confirmed that MB treatment directly reduced IL-1β and increased IL-10 messenger ribonucleic acid in microglia. Last, functional recovery and depressive-like behavior were assessed up to one week after TBI. MB intervention did not prevent TBI-induced reductions in body weight or motor coordination 1-7 d post injury. Nonetheless, MB attenuated the development of acute depressive-like behavior at 7 d post injury. Taken together, immediate intervention with MB was effective in reducing neuroinflammation and improving behavioral recovery after diffuse brain injury. Thus, MB intervention may reduce life-threatening complications of TBI, including edema and neuroinflammation, and protect against the development of neuropsychiatric complications.

Objectives We investigated the impact of anemia based on admission hemoglobin (Hb) level as a prognostic risk factor for severe outcomes in hospitalized patients with coronavirus disease 2019 (COVID-19). Methods A single-center, retrospective cohort study was conducted from a random sample of 733 adult patients (age ≥ 18 years) obtained from a total of 4356 laboratory confirmed SARS-CoV-2 cases who presented to the Emergency Department of Montefiore Medical Center between March–June 2020. The primary outcome was a composite endpoint of in-hospital severe outcomes of COVID-19. A secondary outcome was in-hospital all-cause mortality. Results Among the 733 patients included in our final analysis, 438 patients (59.8%) presented with anemia. 105 patients (14.3%) had mild, and 333 patients (45.5%) had moderate-severe anemia. Overall, 437 patients (59.6%) had a composite endpoint of severe outcomes. On-admission anemia was an independent risk factor for all-cause mortality, (Odds Ratio 1.52, 95% CI [1.01–2.30], p = 0.046) but not for composite severe outcomes. However, moderate-severe anemia (Hb < 11 g/dL) on admission was independently associated with both severe outcomes (OR1.53, 95% CI [1.05–2.23], p = 0.028) and mortality (OR 1.67, 95% CI [1.09–2.56], p = 0.019) during hospitalization. Conclusion Anemia on admission was independently associated with increased odds of all-cause mortality in patients hospitalized with COVID-19. Furthermore, moderate-severe anemia (Hb <11 g/dL) was an independent risk factor for severe COVID-19 outcomes. Moving forward, COVID-19 patient management and risk stratification may benefit from addressing anemia on admission.

Background Appendectomy for acute appendicitis is the most common procedure performed emergently by general surgeons in the United States. The current management of acute appendicitis is increasingly controversial as non-operative management gains favor. Although rare, appendiceal neoplasms are often found as an incidental finding in the setting of appendectomy. Criteria and screening for appendiceal neoplasms are not standardized among surgical societies. Methods The National Surgical Quality Improvement Program (NSQIP) database was queried for all patients who underwent appendectomy over a 9-year period (2010–2018). Over the same time period, patients who underwent appendectomy in two municipal hospitals in The Bronx, New York City, USA were reviewed. Results We found a 1.7% incidence of appendiceal neoplasms locally and a 0.53% incidence of appendiceal tumors in a national population sample. Both groups demonstrated an increased incidence of appendiceal carcinoma by age. This finding was most pronounced after the age of 40 in both local and national populations. In our study, the incidence of appendiceal tumors increased with each decade interval up to the age of 80 and peaked at 2.1% in patients between 70 and 79 years. Conclusions Appendiceal adenocarcinomas were identified in patients with acute appendicitis that seem to be associated with increasing age. The presence of an appendiceal malignancy should be considered in the management of older patients with acute appendicitis before a decision to embark on non-operative therapy.