This randomized trial demonstrates that ATP has beneficial effects on weight, muscle strength, and QOL in patients with advanced NSCLC.

Key Points• The incidence of acute HEV infection after alloHSCT is relatively low, in contrast to a high probability of developing chronic hepatitis.• HEV infection or reactivation should be included in the differential diagnosis of liver enzyme abnormalities in alloHSCT recipients.Hepatitis E virus (HEV) is increasingly acknowledged as a cause of hepatitis in healthy individuals as well as immunocompromised patients. Little is known of HEV infection in recipients of allogeneic hematopoietic stem cell transplantation (alloHSCT). Therefore, we set out to study the incidence and sequelae of HEV as a cause of hepatitis in a recent cohort of 328 alloHSCT recipients. HEV RNA was tested in episodes of liver enzyme abnormalities. In addition, HEV RNA and HEV serology were assessed pre-and postalloHSCT. We found 8 cases (2.4%) of HEV infection, of which 5 had developed chronic HEV infection. Seroprevalence pre-alloHSCT was 13%. Four patients died with HEV viremia, with signs of ongoing hepatitis, having a median time of infection of 4.1 months. The 4 surviving patients cleared HEV after a median period of 6.3 months. One patient was diagnosed with HEV reactivation after a preceding infection prior to alloHSCT. Although the incidence of developing acute HEV post-alloHSCT is relatively low, the probability of developing chronic hepatitis in severely immunocompromised patients is high. Therefore, alloHSCT recipients should be screened pretransplantation by HEV serology and RNA. Furthermore, a differential diagnosis including hepatitis E is mandatory in all alloHSCT patients with severe liver enzyme abnormalities. (Blood. 2013;122(6):1079-1086

During constant i.v. infusion of ATP in lung cancer patients, ATP is taken up by erythrocytes and reaches dose-dependent plateau levels 50-70% above basal concentrations at approximately 24 h.

We recently reported that regular infusions of adenosine 5'-triphosphate (ATP) inhibited loss of body weight and quality of life in patients with non-small cell lung cancer (NSCLC). In the present paper we investigated whether ATP affects tumor growth and survival in the same group of patients. Fifty-eight NSCLC patients (stage IIIB or IV) were randomly assigned to receive either 10 i.v. 30-h ATP infusions every 2-4 weeks over a 24-week period (n = 28) or no ATP (control patients, n = 30). ATP was given for a median of 6.5 infusions. Differences in time to progression and survival between patients in both groups were tested by means of the log-rank test and Cox regression analysis. Forty-nine patients were evaluable for tumor response. None of the evaluable patients showed a complete or partial response. Median time to progression was 3.9 months [95% confidence interval (CI) = 2.3-5.5] in the ATP group compared to 3.0 months (95% CI = 2.4-3.7) in the control group (p = 0.71). Median survival was 5.6 months (95% CI = 1.1-10.1) for the ATP group and 4.7 months (95% CI = 2.6-6.8) for the control group (p = 0.68). ATP treatment was associated with a significant increase in survival in the subgroup of weight-losing patients with stage IIIB NSCLC: in this subgroup, median survival was 9.3 months (95% CI = 2.1-16.5) for ATP-treated patients versus 3.5 months (95% CI = 2.3-4.7) for control patients (between-group difference: p = 0.009). No significant effect of ATP was observed for weight-losing patients with stage IV NSCLC or for weight-stable NSCLC patients. Although ATP as a single therapy does not lead to tumor regression or increased survival in patients with advanced lung cancer, it may prolong survival in weight-losing patients with stage IIIB lung cancer. The latter finding is intriguing, but requires confirmation in larger clinical trials.

Adenosine 5'-triphosphate (ATP) is a purine nucleotide found in every cell of the human body. In addition to its well established role in cellular metabolism, extracellular ATP and its breakdown product adenosine, exert pronounced effects in a variety of biological processes including neurotransmission, muscle contraction, cardiac function, platelet function, vasodilatation and liver glycogen metabolism. These effects are mediated by both P1 and P2 receptors. A cascade of ectonucleotidases plays a role in the effective regulation of these processes and may also have a protective function by keeping extracellular ATP and adenosine levels within physiological limits. In recent years several clinical applications of ATP and adenosine have been reported. In anaesthesia, low dose adenosine reduced neuropathic pain, hyperalgesia and ischaemic pain to a similar degree as morphine or ketamine. Postoperative opioid use was reduced. During surgery, ATP and adenosine have been used to induce hypotension. In patients with haemorrhagic shock, increased survival was observed after ATP treatment. In cardiology, ATP has been shown to be a well tolerated and effective pulmonary vasodilator in patients with pulmonary hypertension. Bolus injections of ATP and adenosine are useful in the diagnosis and treatment of paroxysmal supraventricular tachycardias. Adenosine also allowed highly accurate diagnosis of coronary artery disease. In pulmonology, nucleotides in combination with a sodium channel blocker improved mucociliary clearance from the airways to near normal in patients with cystic fibrosis. In oncology, there are indications that ATP may inhibit weight loss and tumour growth in patients with advanced lung cancer. There are also indications of potentiating effects of cytostatics and protective effects against radiation tissue damage. Further controlled clinical trials are warranted to determine the full beneficial potential of ATP, adenosine and uridine 5'-triphosphate.

The inhibition of weight loss by ATP infusions in patients with advanced NSCLC is attributed to counteracting the loss of both metabolically active and inactive tissues. These effects are partly ascribed to maintenance of energy intake.

We recently observed inhibition of weight loss in patients with advanced nonsmall-cell lung cancer after intravenous infusion of ATP. Because liver ATP levels were found to be decreased in lung cancer patients with weight loss, the present 31 P magnetic resonance spectroscopy (MRS) study was aimed at investigating whether ATP infusion restores liver energy status in these patients. Nine patients with advanced nonsmall-cell lung cancer (stage IIIB/ IV) were studied 1 week before (baseline) and at 22 to 24 hours of continuous ATP infusion (37-75 g/kg/min). Localized hepatic 31 P MR spectra (repetition time 15 seconds), obtained in the overnight-fasted state, were analyzed for ATP and P i content. Ten healthy subjects (without ATP infusion) served as control. Liver ATP levels in lung cancer patients increased from 8.8 ؎ 0.7% (relative to total MR-detectable phosphate; mean ؎ SE) at baseline to 12.2 ؎ 0.9% during ATP infusion (P < .05), i.e., a level similar to that in healthy subjects (11.9 ؎ .9%). The increase in ATP level during ATP infusion was most prominent in patients with >5% weight loss (baseline: 7.9 ؎ 0.7%, during ATP infusion: 12.8 ؎ 1.0%, P < .01). In conclusion, ATP infusion restores hepatic energy levels in patients with advanced lung cancer, especially in weight-losing patients. These changes may contribute to the previously reported beneficial effects of ATP infusion on the nutritional status of lung cancer patients. (HEPATOLOGY 2002;35:421-424.) W eight loss is a common phenomenon in lung cancer patients and contributes significantly to the high morbidity and mortality in this disease. 1,2 Alterations in intermediary host metabolism have been frequently described, including elevated protein turnover, 3,4 glucose production, 5,6 and Cori cycle activity. 7 In an in vitro study, gluconeogenesis in isolated hepatocytes from sarcoma-bearing rats was increased during incubation with lactate, resulting in a 42% decrease in adenosine triphosphate (ATP) levels, as compared with hepatocytes from healthy rats (no change in ATP). 8 This suggests that elevated rates of gluconeogenesis in the cancer-bearing host put an increased demand on the energy stores and contribute to weight loss.Alterations in hepatic energy status have been well documented in animal models of various tumors. Decreased liver phosphorylation status, as observed by increased P i /ATP ratios, was detected in rats bearing prostate tumors 9 or sarcomas 10-12 and was correlated with increasing tumor burden. 10 Increased P i /ATP ratios may indicate a decreased energy-regenerating capacity within the hepatocytes of the cancer-bearing host. 8 It is noteworthy that these alterations in liver energy status were already detected before the development of weight loss. 13 Decreased liver ATP levels as detected by 31 P magnetic resonance spectroscopy (MRS) were reported in patients with various tumor types. 14 Recently, we reported decreased hepatic ATP and phosphorylation status in weight-losing lung cancer patients, when compared with weight-stabl...

No abstract