The association between gut microbiome affecting concomitant medication and the effectiveness of immunotherapy in patients with stage IV NSCLC.

Several observational studies suggested that gut microbiome-affecting-medication impairs the effectiveness of immunotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). We postulated that if the effectiveness of immunotherapy is affected by drug-related changes of the microbiome, a stronger association between the use of co-medication and overall survival (OS) will be observed in patients treated with immunotherapy as compared to patients treated with chemotherapy. In a retrospective matched cohort study, immunotherapy patients were matched (1:1) to patients treated with chemotherapy in the pre immunotherapy era. The association between the use of antibiotics, opioids, proton pump inhibitors, metformin and other antidiabetics on OS was assessed with multivariable cox-regression analyses. Interaction tests were applied to investigate whether the association differs between patients treated with immuno- or chemotherapy. A total of 442 patients were studied. The use of antibiotics was associated with worse OS (adjusted Hazard Ratio (aHR) 1.39, p = 0.02) independent of the type of therapy (chemotherapy or immunotherapy). The use of opioids was also associated with worse OS (aHR 1.33, p = 0.01). The other drugs studied showed no association with OS. Interaction term testing showed no effect modification by immuno- or chemotherapy for the association of antibiotics and opioids with OS. The use of antibiotics and opioids is similarly associated with worse outcomes in both chemotherapy and immunotherapy treated NSCLC patients. This suggests that the association is likely to be a consequence of confounding rather than disturbing the composition of the microbiome.

[Treating poisoning; how do you choose the best type of gastrointestinal decontamination?] / De behandeling van vergiftigingen.

- A new guideline: 'Intoxication: initial approach in the hospital' will be published this year. This guideline sets out the latest insights on gastrointestinal decontamination in intoxication; the advice is summarized in a flowchart.- The advice is to generally administer activated charcoal, unless there are indications that the toxin will not bind to activated charcoal or that the amount of toxin that the patient has ingested is too great; in these cases gastric lavage can be considered.- Activated charcoal can be administered up to 2 hours after the ingestion of a toxic substance, unless there are contra-indications. Multiple-dose activated charcoal in combination with a laxative can be administered in cases of overdose with toxins that use the enterohepatic circulation (such as theophylline, carbamazepine, quinine, dapsone and phenobarbital).- Gastric lavage should be limited to extremely serious intoxication, when the substance has been ingested less than 1-2 hours previously.- Whole-bowel irrigation should not be performed routinely but should be limited to ingestion of toxins with sustained release or enteric coating, or for toxins that do not bind to activated charcoal.