In-hospital perforation risk in acute appendicitis: Age matters.

BACKGROUND: Controversy exists regarding how quickly an adult with appendicitis requires surgery to prevent perforation, and recent literature on antibiotic use as definitive treatment has complicated this question further. Since perforation is associated with worse outcomes, particularly in the elderly, efforts to prevent this complication are warranted. We studied risk factors for in-hospital perforation in patients diagnosed by admission CT with non-perforated acute appendicitis. METHODS: We evaluated baseline demographics, symptom duration, and time from admission to antibiotics and surgery. Outcome measure was perforation diagnosed intra-operatively by attending surgeon. RESULTS: Of 700 patients, 84 (12%) sustained in-hospital perforation; time from admission to operation or antibiotics were not associated. Duration of symptoms >24 h (aOR = 2.23, 95% CI = 1.33-3.72, p < 0.001) increased perforation risk. Patient age over 46 years (aOR = 4.54, 95% CI = 2.04-10.06, p < 0.001) was also associated with higher risk that increased with increasing age. CONCLUSION: Time to operation and antibiotic timing were not associated with in-hospital perforation in a general adult population. However, these findings suggest a possible benefit to expedient surgery in older patients.

Rehabilitative Training Interacts with Ischemia-Instigated Spine Dynamics to Promote a Lasting Population of New Synapses in Peri-Infarct Motor Cortex.

After subtotal infarcts of primary motor cortex (M1), motor rehabilitative training (RT) promotes improvements in paretic forelimb function that have been linked with its promotion of structural and functional reorganization of peri-infarct cortex, but how the reorganization unfolds is scantly understood. Cortical infarcts also instigate a prolonged period of dendritic spine turnover in peri-infarct cortex. Here we investigated the possibility that synaptic structural responses to RT in peri-infarct cortex reflect, in part, interactions with ischemia-instigated spine turnover. This was tested after artery-targeted photothrombotic M1 infarcts or Sham procedures in adult (4 months) C57BL/6 male and female GFP-M line (n = 24) and male yellow fluorescent protein-H line (n = 5) mice undergoing RT in skilled reaching or no-training control procedures. Regardless of training condition, spine turnover was increased out to 5 weeks postinfarct relative to Sham, as was the persistence of new spines formed within a week postinfarct. However, compared with no-training controls, new spines formed during postinfarct weeks 2-4 in mice undergoing RT persisted in much greater proportions to later time points, by a magnitude that predicted behavioral improvements in the RT group. These results indicate that RT interacts with ischemia-instigated spine turnover to promote preferential stabilization of newly formed spines, which is likely to yield a new population of mature synapses in peri-infarct cortex that could contribute to cortical functional reorganization and behavioral improvement. The findings newly implicate ischemia-instigated spine turnover as a mediator of cortical synaptic structural responses to RT and newly establish the experience dependency of new spine fates in the postischemic turnover context.SIGNIFICANCE STATEMENT Motor rehabilitation, the main treatment for motor impairments after stroke, is far from sufficient to normalize function. A better understanding of neural substrates of rehabilitation-induced behavioral improvements could be useful for understanding how to optimize it. Here, we investigated the nature and time course of synaptic responses to motor rehabilitative training in vivo Focal ischemia instigated a period of synapse turnover in peri-infarct motor cortex of mice. Rehabilitative training increased the stability of new synapses formed during the initial weeks after the infarct, the magnitude of which was correlated with improvements in skilled motor performance. Therefore, the maintenance of new synapses formed after ischemia could represent a structural mechanism of rehabilitative training efficacy.

Effect of non-steroidal anti-inflammatory drugs on post-surgical complications against the backdrop of the opioid crisis.

The USA is currently going through an opioid crisis, associated with tremendous economic and societal impacts. In response to this crisis, healthcare professionals are looking for alternative pain management methods, and non-steroidal anti-inflammatory drugs (NSAIDs) are a sensible choice because of their effectiveness after surgical procedures. However, before surgeons start prescribing NSAIDs in place of opioids, it is crucial to first understand their potential post-surgical complications. The goal of this review is to summarize the data obtained through both animal and human studies, which suggest how a dramatic increase in NSAID use may affect these post-surgical complications. We first provide a short review outlining the mechanisms of action of NSAIDs, followed by a summary of animal studies, which show a trend towards the negative effects of NSAIDs on wound healing and an association between NSAID use and wound infections. Lastly, we present evidence from human studies on the association of NSAIDs with the following complications: anastomotic leaks, necrotizing soft tissue infections, bleeding complications, orthopedic injuries, wound healing, and cancer care. The human studies are much more variable in their conclusions as to whether NSAIDs are beneficial or not, with the only strong evidence showing that NSAIDs inhibit bone healing. This may partially be explained by male and female differences in response to NSAIDs as many animal studies showing the inhibitory effects of NSAIDs were performed on females, while all the human studies were performed with both sexes. We conclude that strong caution should be used in the prescription of NSAIDs, especially in female patients, but larger scale studies are warranted before solid recommendations can be made.

RERE deficiency leads to decreased expression of GATA4 and the development of ventricular septal defects.

Deletions of chromosome 1p36 are associated with a high incidence of congenital heart defects (CHDs). The arginine-glutamic acid dipeptide repeats gene (RERE) is located in a critical region for CHD on chromosome 1p36 and encodes a cardiac-expressed nuclear receptor co-regulator. Mutations affecting RERE cause atrial and ventricular septal defects (VSDs) in humans, and RERE-deficient mice also develop VSDs. During cardiac development, mesenchymal cells destined to form part of the atrioventricular (AV) septum are generated when endocardial cells in the AV canal undergo epithelial-to-mesenchymal transition (EMT) and migrate into the space between the endocardium and the myocardium. These newly generated mesenchymal cells then proliferate to fill the developing AV endocardial cushions. Here, we demonstrate that RERE-deficient mouse embryos have reduced numbers of mesenchymal cells in their AV endocardial cushions owing to decreased levels of EMT and mesenchymal cell proliferation. In the endocardium, RERE colocalizes with GATA4, a transcription factor required for normal levels of EMT and mesenchymal cell proliferation. Using a combination of in vivo and in vitro studies, we show that Rere and Gata4 interact genetically in the development of CHDs, RERE positively regulates transcription from the Gata4 promoter and GATA4 levels are reduced in the AV canals of RERE-deficient embryos. Tissue-specific ablation of Rere in the endocardium leads to hypocellularity of the AV endocardial cushions, defective EMT and VSDs, but does not result in decreased GATA4 expression. We conclude that RERE functions in the AV canal to positively regulate the expression of GATA4, and that deficiency of RERE leads to the development of VSDs through its effects on EMT and mesenchymal cell proliferation. However, the cell-autonomous role of RERE in promoting EMT in the endocardium must be mediated by its effects on the expression of proteins other than GATA4.This article has an associated First Person interview with the first author of the paper.