Prevalence and outcomes of Clostridioides difficile infection in liver transplant recipients.

BACKGROUND AND AIM: Data are limited on whether Clostridioides difficile infection (CDI) in the first year after liver transplantation (LT) is associated with increased mortality. In an Australian setting without hypervirulent strain of C. difficile we investigated the prevalence, risk factors, and patient survival associated with CDI in LT. METHODS: Consecutive patients who underwent deceased-donor LT from 2007 to 2017 were studied retrospectively. Prevalence and long-term outcomes of LT recipients with and without CDI were examined in the entire LT cohort. A case-control study was performed to investigate risk factors associated with CDI. RESULTS: Six hundred and forty-nine patients underwent LT, of which 32 (4.9%) were diagnosed with CDI within the first 12 months post-LT. There was no difference in patient survival in the overall LT cohort on Kaplan-Meier analysis when stratified by CDI status (log-rank test, p = .08). Furthermore, age was the only predictor of mortality on Cox regression (hazard ratio (HR) 1.06, 95% confidence interval (CI) 1.00-1.13, p = .03). On multivariable logistic regression, rifaximin pre-LT reduced risk (odds ratio (OR) 0.22, 95% CI 0.65-0.74, p = .01) whereas antibiotics pre-LT (OR 7.02, 95% CI 1.26-39.01, p = .03) and length of hospital stay after LT (OR 1.03, 95% CI 1.01-1.06, p = .02) were associated with increased risk of CDI. CONCLUSIONS: Within the local setting of our study, CDI within 12 months post-LT is of low severity, associated with pre-LT antibiotic exposure and longer hospital stay but no survival impact after LT. Rifaximin use pre-LT reduced the risk of CDI post-LT.

Alcohol use disorder and the gut.

Acute and chronic gastrointestinal problems are common in the setting of excessive alcohol use, and excessive alcohol use is associated with injury to all parts of the gastrointestinal tract. There is mounting evidence of gastrointestinal injury and increased cancer risk even from moderate alcohol consumption. The major causes of alcohol-related morbidity and mortality within the gastrointestinal system are liver disease, pancreatitis and gastrointestinal cancer. Other alcohol-related intestinal dysfunction is common but not life-threatening, leading to diarrhoea, malabsorption and nutritional deficiencies. This review describes non-neoplastic and neoplastic alcohol-related disorders of the gastrointestinal tract, omitting the liver, which has been reviewed elsewhere.

The position of an arginine residue influences substrate affinity and K+ coupling in the human glutamate transporter, EAAT1.

Glutamate is the predominant excitatory neurotransmitter in the mammalian central nervous system and extracellular glutamate levels are controlled by a family of transporters known as excitatory amino acid transporters (EAATs). The EAATs transport glutamate and aspartate with similar micromolar affinities and this transport is coupled to the movement of Na(+), K(+), and H(+). The crystal structure of a prokaryotic homologue of the EAATs, aspartate transporter from Pyrococcus horokoshii (Glt(Ph)), has yielded important insights into the architecture of this transporter family. Glt(Ph) is a Na(+)-dependent transporter that has significantly higher affinity for aspartate over glutamate and is not coupled to H(+) or K(+). The highly conserved carboxy-terminal domains of the EAATs and Glt(Ph) contain the substrate and ion binding sites, however, there are a couple of striking differences in this region that we have investigated to better understand the transport mechanism. An arginine residue is in close proximity to the substrate binding site of both Glt(Ph) and the EAATs, but is located in transmembrane domain (TM) 8 in the EAATs and hairpin loop 1 (HP1) of Glt(Ph). Here we report that the position of this arginine residue can explain some of the functional differences observed between the EAATs and Glt(Ph). Moving the arginine residue from TM8 to HP1 in EAAT1 results in a transporter that has significantly increased affinity for both glutamate and aspartate and is K(+) independent. Conversely, moving the arginine residue from HP1 to TM8 in Glt(Ph) results in a transporter that has reduced affinity for aspartate.