Hepatic Artery Aneurysm/Pseudoaneurysm: An Unusual Cause of Upper Gastrointestinal (UGI) Bleeding and Biliary Obstruction Further Complicated by Glue Dislodgement Leading to Biliary Obstruction.

Hepatic artery aneurysms (HAA) and pseudoaneurysms are rare vascular abnormalities, that can lead to significant morbidity and mortality if left untreated. We present a case report of a 78-year-old lady with a hepatic artery aneurysm who initially presented with upper gastrointestinal bleeding (UGIB) and biliary obstruction and was treated by trans-arterial embolization. Recovery was complicated by glue embolisation leading to obstructive jaundice and biliary sepsis. This case highlights the importance of having a high index of suspicion for HAA and pseudoaneurysm when initial investigations including oesophago gastro duodenoscopy (OGD) are negative. Although rare, glue embolization should be considered in patients who present with obstructive jaundice and abdominal pain.

Mutators can drive the evolution of multi-resistance to antibiotics.

Antibiotic combination therapies are an approach used to counter the evolution of resistance; their purported benefit is they can stop the successive emergence of independent resistance mutations in the same genome. Here, we show that bacterial populations with 'mutators', organisms with defects in DNA repair, readily evolve resistance to combination antibiotic treatment when there is a delay in reaching inhibitory concentrations of antibiotic-under conditions where purely wild-type populations cannot. In populations of Escherichia coli subjected to combination treatment, we detected a diverse array of acquired mutations, including multiple alleles in the canonical targets of resistance for the two drugs, as well as mutations in multi-drug efflux pumps and genes involved in DNA replication and repair. Unexpectedly, mutators not only allowed multi-resistance to evolve under combination treatment where it was favoured, but also under single-drug treatments. Using simulations, we show that the increase in mutation rate of the two canonical resistance targets is sufficient to permit multi-resistance evolution in both single-drug and combination treatments. Under both conditions, the mutator allele swept to fixation through hitch-hiking with single-drug resistance, enabling subsequent resistance mutations to emerge. Ultimately, our results suggest that mutators may hinder the utility of combination therapy when mutators are present. Additionally, by raising the rates of genetic mutation, selection for multi-resistance may have the unwanted side-effect of increasing the potential to evolve resistance to future antibiotic treatments.