Invasive Fungal Infections in Low-Risk Liver Transplant Recipients: A Multi-Center Prospective Observational Study

Prevention of invasive fungal infections (IFIs) in orthotopic liver transplant (OLT) recipients utilizing postoperative systemic antifungal prophylaxis, typically with fluconazole, is justified among those at high risk for IFI. Use of postoperative antifungal prophylaxis for low-risk OLT recipients is widely practiced but not universally accepted nor supported by data. We conducted a prospective observational study among 200 OLT recipients who were at low risk for IFI and did not receive postoperative antifungal prophylaxis. Patients were considered low risk if they had /=units of 40 blood products or return to the operating room for intra-abdominal bleeding; return to the operating room for anastomotic leak or vascular insufficiency; preoperative serum creatinine of >/=2 mg/dL; and perioperative Candida colonization. Patients were followed 100 d post-transplantation for evidence of IFI. Of 193 eligible patients, 7 (4%) developed an IFI. Three (2%) IFIs were due to Candida spp. and potentially preventable by standard fluconazole prophylaxis. Three patients developed invasive aspergillosis; one developed late onset disseminated cryptococcosis. Liver transplant recipients at low risk for IFI can be identified utilizing pre-determined criteria, and post-transplantation antifungal prophylaxis can be routinely withheld in these patients.     

Age and gender effects on submental motor-evoked potentials

It is not known whether there are age- and/or gender-related differences in magnitude of motor-evoked potentials (MEPs) of the submental muscles. Knowledge of this is important in investigations of neurophysiological aspects of swallowing. Forty healthy participants (20 males, 20 females; 20 young [21–35 years], 20 old [53–88 years]) were recruited. Surface electromyography (EMG) electrodes were placed at midline underlying the submental muscle group. Age- and gender-related differences were evaluated in two neurophysiologic measures of swallowing: MEPs stimulated by single-pulse transcranial magnetic stimulation (TMS) over the motor cortex and surface electromyography (sEMG) recorded from the same submental muscle group during non-stimulated swallows. The older participants had larger MEPs during saliva swallowing than the young participants (p = 0.04, d = 0.86). Conversely, the older participants had lower amplitude submental EMG activity during non-stimulated swallows (p = 0.045, d = 0.67). Gender had no significant effect on MEP magnitude and on submental activity during saliva swallowing. There were no effects of age or gender on MEP latencies. These findings suggest deterioration in muscle function with age in a sample of healthy adults presenting with functional swallowing. We speculate that muscular decline is partially ameliorated by increased cortical activity—i.e., increased submental MEPs—so as to preserve swallowing function in healthy older subjects. These findings emphasize the need for different reference points for evaluation of submental MEPs of different age groups.     

Amino acid metabolism in lactic acidosis

Individual plasma amino acid levels have been determined in six patients with severe lactic acidosis. A consistently distorted pattern was observed whether the disorder was due to shock or was of the idiopathic type. A sixfold elevation in mean alanine concentration was observed, and a significant correlation of alanine with pyruvate concentrations was demonstrated. Since alanine is normally released from muscle and stoichiometrically extracted by liver, normal formation of alanine from pyruvate is suggested by the findings. However, uptake and metabolism of alanine by isolated, perfused rat liver was significantly inhibited by perfusate concentrations of lactate and pyruvate equivalent to those observed in the patients. Thus the high levels of alanine in lactic acidosis are viewed as consistent with normal or increased peripheral release combined with impaired hepatic disposal. The levels of fifteen of the nineteen amino acids measured were elevated. Of the remaining four, three were intermediates of the urea cycle.     

Abnormal resting blood lactate I. The significance of hyperlactatemia in hospitalized patients

1. 1. When patients on a hospital ward were studied to determine the range of blood lactate concentrations to be found, the values varied from 0.430 to 26.42 mM/L.

2. 2. A very small part of this variation was caused by the imperfect sampling technics necessary for bedside use.

3. 3. Only a very small part of the variation could be accounted for by muscular contractions in any patient who was lying still in bed.

4. 4. However, great elevations of blood lactate occasionally occurred in resting patients. These were encountered in a variety of clinical states which seemed to have nothing in common, and other patients with similar diseases showed no similar lactatemia in association with the disease itself.

5. 5. The patients with hyperlactatemia had variable blood pyruvate concentrations; in some patients the elevated pyruvate level accounted for the elevated lactate, through its effects in the lactic dehydrogenase system, while in other patients there appeared to be a major accumulation of lactate in excess of this and due to some other cause. On this basis the patients were divided into groups 1 and 2.

6. 6. Since the only other cause of a steady state of lactate accumulation is cellular hypoxia, data on circulation and respiration were collected. On this basis group 2 was further subdivided into groups A and B, the former including all patients with hypoxemia or circulatory failure.

7. 7. All patients with hyperlactatemia except the small group 2B were found to exhibit the various known causes of lactate accumulation consistent with the accompanying changes in blood pyruvate but often only indirectly and incidentally related to the “disease” for which hospital admission was required.

8. 8. Group 2B could not be satisfactorily explained in any clinical terms or in relation to other laboratory findings, but the group was nevertheless clinically distinct. All the patients were acidotic and all died.