Risk Factors for Nontuberculous Mycobacteria Infections in Solid Organ Transplant Recipients: A Multinational Case-Control Study.

BACKGROUND: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. METHODS: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. RESULTS: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection. CONCLUSIONS: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.

Where Are We Now and Where Might We Be Headed in Understanding and Managing Brain Metastases in Colorectal Cancer Patients?

OPINION STATEMENT: Compared to liver and lung metastases, brain metastases (BMs) from colorectal cancer (CRC) are rare and remain poorly investigated despite the anticipated rise in their incidence. CRC patients bearing BM have a dismal prognosis with a median survival of 3-6 months, significantly lower than that of patients with BM from other primary tumors, and of those with metastatic CRC manifesting extracranially. While liver and lung metastases from CRC have more codified treatment strategies, there is no consensus regarding the treatment of BM in CRC, and their management follows the approaches of BM from other solid tumors. Therapeutic strategies are driven by the number and localisation of the lesion, consisting in local treatments such as surgery, stereotactic radiosurgery, or whole-brain radiotherapy. Novel treatment modalities are slowly finding their way into this shy unconsented armatorium including immunotherapy, monoclonal antibodies, tyrosine kinase inhibitors, or a combination of those, among others.This article reviews the pioneering strategies aiming at understanding, diagnosing, and managing this disease, and discusses future directions, challenges, and potential innovations in each of these domains. HIGHLIGHTS: • With the increasing survival in CRC, brain and other rare/late-onset metastases are rising. • Distal colon/rectal primary location, long-standing progressive lung metastases, and longer survival are risk factors for BM development in CRC. • Late diagnosis and lack of consensus treatment strategies make BM-CRC diagnosis very dismal. • Liquid biopsies using circulating tumor cells might offer excellent opportunities in the early diagnosis of BM-CRC and the search for therapeutic options. • Multi-modality treatment including surgical metastatic resection, postoperative SRS with/without WBRT, and chemotherapy is the best current treatment option. • Recent mid-sized clinical trials, case reports, and preclinical models show the potential of unconventional therapeutic approaches as monoclonal antibodies, targeted therapies, and immunotherapy. Graphical abstract.