Late Onset of Rivaroxaban-Associated Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis.

Although anti-thyroid drugs (ATDs) are the most common cause of drug-associated anti-neutrophil cytoplasmic antibody (ANCA) vasculitis (AAV), many other classes of drugs can lead to drug-associated AAV. We present a unique case of rivaroxaban-associated AAV. A 76-year-old female with a past medical history of atrial fibrillation on rivaroxaban presented with fatigue, bilateral lower extremity purpura, and hemoptysis to an outside hospital. Investigations revealed a positive cytoplasmic-ANCA (c-ANCA) titer of 1:320 and a positive anti-myeloperoxidase (anti-MPO), and negative perinuclear-ANCA (p-ANCA) and anti-proteinase 3 (anti-PR3). In addition, chest imaging demonstrated bilateral ground-glass opacities which raised suspicion for diffuse alveolar hemorrhage (DAH). A lung biopsy revealed acute and ongoing DAH with focally active capillaritis and characteristic pathological findings, which strongly suggested that was likely secondary to rivaroxaban. Rivaroxaban was discontinued, and the patient received pulses of intravenous glucocorticosteroids and rituximab. Her symptoms improved. She continued immunosuppressive therapy with rituximab for 2 years. She presented to our hospital for a second opinion regarding the discontinuation of rituximab, and we decided to discontinue rituximab. After discontinuation, the patient remained stable after 1.5 years of follow-up and did not have any relapses. This is a unique case of rivaroxaban-associated AAV. Clinicians should consider drug-associated AAV in all patients who present with an atypical clinical presentation and/or pathological findings of AAV. Given the broad and rapidly increasing use of novel anticoagulants, it is important to raise awareness of this potential complication. Prompt discontinuation of the drug and initiation of immunosuppressant treatment in severe cases may be lifesaving.

The role of chemical fractionation in risk assessment of toxic metals: a review.

The identification of highly toxic metals like Cd, Ni, Pb, Cr, Co or Cu in ambient particulate matter (PM) has garnered a lot of interest recently. Exposure to toxic metals, including carcinogenic ones, at levels above recommended limits, can significantly affect human health. Prolonged exposure to even trace amounts of toxic or essential metals can also have negative health impacts. In order to assess significant risks, it is crucial to govern the concentrations of bioavailable/bio-accessible metals that are available in PM. Estimating the total metal concentrations in PM is only an approximation of metal toxicity. This review provides an overview of various procedures for extracting soluble toxic metals from PM and the importance of chemical fractionation in risk assessment. It is observed that the environmental risk indices such as bioavailability index (BI), contamination factor (CF) and risk assessment code (RAC) are specifically influenced by the concentration of these metals in a particular fraction. Additionally, there is compelling evidence that health risks assessed using total metal concentrations may be overestimated, therefore, the metal toxicity assessment is more accurate and more sensitive to the concentration of the bioavailable/bio-accessible fraction than the total metal concentrations. Hence, chemical fractionation of toxic metals can serve as an effective tool for developing environmental protection laws and improving air quality monitoring programs for public health.

Chemoimmunotherapy in patients with extensive-stage small cell lung cancer and a poor performance status.

BACKGROUND: Immune checkpoint inhibitor combined with platinum-etoposide is the standard first-line therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The phase 3 clinical trials that led to the approval of chemoimmunotherapy in ES-SCLC excluded patients who had an Eastern Cooperative Group (ECOG) performance status (PS) of 2-3. Therefore, data on the efficacy of chemoimmunotherapy in patients with an ECOG PS of 2-3 are limited. METHODS: A retrospective analysis was performed on patients diagnosed with ES-SCLC who received chemoimmunotherapy (atezolizumab or durvalumab) within the Mayo Clinic Health System between January 2016 and January 2021. The objective of this study was to compare the overall survival (OS), progression-free survival (PFS), and best clinical response to therapy in patients with an ECOG PS of 0-1 vs. patients with an ECOG PS of 2-3 who received chemoimmunotherapy for newly diagnosed ES-SCLC. RESULTS: In total, 82 patients were included in the study. The mean ± standard deviation age was 68.1 ± 8.3 years. Of these, 56 patients were identified with an ECOG PS of 0-1, and 26 patients were identified with an ECOG PS of 2-3. The median PFS was similar regardless of ECOG PS (5.8 months [95% CI, 4.3-6.0 months] in the ECOG PS 0-1 group vs. 4.1 months [95% CI, 3.8-6.9 months] in the ECOG PS 2-3; p = .2994). The median OS was also similar regardless of ECOG PS (10.6 months [95% CI, 8.4-13.4 months] in the ECOG PS 0-1 group vs. 9.3 months [95% CI, 4.9-12.8 months]; p = .2718) in the ECOG PS 2-3 group. CONCLUSIONS: The study results demonstrated no significant difference in PFS or OS among the ECOG PS 2-3 and ECOG PS 0-1 groups. Therefore, chemoimmunotherapy should be considered for patients who have ES-SCLC with an ECOG PS of 2-3.

Chemoimmunotherapy as the First-Line Treatment for Patients With Extensive-Stage Small-Cell Lung Cancer and an ECOG Performance Status 2 or 3.

BACKGROUND: Studies demonstrated that chemoimmunotherapy prolongs progression-free survival (PFS) and overall survival (OS) in patients with extensive-stage small-cell lung cancer (ES-SCLC) and an Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. However, there is little data regarding chemoimmunotherapy in patients with ES-SCLC and an ECOG PS 2 or 3. This study aims to evaluate the benefits of chemoimmunotherapy compared to chemotherapy in the first-line treatment of patients with ES-SCLC and ECOG PS 2 or 3. MATERIALS AND METHODS: This retrospective study analyzed 46 adults treated at Mayo Clinic between 2017 and 2020 with de novo ES-SCLC and an ECOG PS 2 or 3. Twenty patients received platinum-etoposide and 26 patients received platinum-etoposide and atezolizumab. Progression-free survival (PFS) and Overall survival (OS) were calculated using Kaplan-Meier methods. RESULTS: PFS was longer in the chemoimmunotherapy group compared to the chemotherapy group, 4.1 months (95% confidence interval [CI]: 3.8-6.9) vs. 3.2 months (95% CI: 0.6-4.8), respectively; P = 0.0491. However, there was no statistically significant difference in the OS between the chemoimmunotherapy and chemotherapy group, 9.3 months (95% CI: : 4.9-12.8) vs. 7.6 months (95% CI: 0.6-11.9), respectively; P = .21. CONCLUSION: Chemoimmunotherapy prolongs PFS compared to chemotherapy in patients with newly diagnosed ES-SCLC and an ECOG PS 2 or 3.  No OS difference was observed among the chemoimmunotherapy and chemotherapy groups; nevertheless, this may be attributed due to the small sample size of the study.

Clinical utility of somatostatin receptor positron emission tomography imaging biomarkers for characterization of meningioma among incidental central nervous system lesions.

OBJECTIVES: Somatostatin receptor (SSTR) PET imaging is utilized with increasing frequency in the clinical management of neuroendocrine tumors. Incidental PET-avid CNS lesions are commonly noted and presumed to be meningiomas. However, SSTR PET lacks specificity for meningioma identification. This study aimed to clarify the role of SSTR-based imaging in the classification of incidental CNS lesions based on current clinical practice. METHODS: Patients who underwent both Ga-68-DOTATATE PET and brain MRI and had an incidental CNS lesion identified with a radiographic prediction of meningioma via one (discordant prediction) or both (concordant prediction) imaging modalities were retrospectively analyzed. Imaging indication, semiquantitative measures, and clinical history were recorded. RESULTS: Among 48 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (64.6%). Cases with concordant lesion-type prediction of meningioma between imaging modalities ( N = 24) displayed a significantly higher SUV max (median 7.9 vs. 4.0; P = 0.008) and Krenning score (median 3.0 vs. 2.0; P = 0.005) on Ga-68-DOTATATE PET compared with cases with a discordant prediction of meningioma ( N = 24). In cases with lower SUV max values, Ga-68-DOTATATE was more likely to discordantly predict meningioma without agreement by the corresponding MRI. Prior cranial radiation or use of somatostatin mimetics did not affect quantitative radiographic measures, and MRI-based tumor size was similar across groups. CONCLUSION: Lesions with increased avidity may be more confidently predicted as meningioma in Ga-68-DOTATATE PET scans, whereas there is more discrepancy in prediction among low SUV cases.