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Context: Recreational drug use is known to cause select histopathologic findings in the lungs. Systemic changes may also be seen in the lungs. There is a paucity of large cohort studies assessing histopathologic findings in the lungs of decedents who abused illicit drugs, prescription drugs, and/or alcohol. Design: We queried institutional autopsy files (1998-2014) for cases with a history of substance abuse (illicit, prescription, and/or alcohol) and/or positive postmortem toxicologic studies. We performed a retrospective review of histologic findings in lungs of these autopsy cases. Histologic findings of the interstitium, vasculature, airways, and pleura were recorded. Autopsy reports, and toxicology and clinical records were reviewed. Frequencies of drug categories and histology were compared by using Fisher exact tests. Results: Seventy-three autopsy cases (50 men with a median age of 45 years) were reviewed. Drug overdose/toxicity was the most common cause of death (53%) followed by blunt force trauma (10%). The most common histologic findings included pigmented macrophages (63%), smoking-related changes (56%), interstitial changes (40%), small airways changes (32%), and acute lung injury (22%). Associations included granulomas with fentanyl toxicity (P = .03) (predominantly nonnecrotizing), pigmented macrophages with positive urine THC result (P = .01), and marijuana abuse history (P = .01) (predominantly coarse, brown pigment), and with stimulant abuse history (P = .03) (generally \"crunchy\" brown pigment), and smoking-related changes with positive urine THC result (P = .02) and stimulant abuse history (P = .01). Conclusions: The identification of such histopathologic findings can help to identify previously unknown drug abuse and/or support a known clinical history of abuse in autopsy cases as well as in the surgical pathology setting.

The accurate identification of different lung adenocarcinoma histologic subtypes is important for determining prognosis but can be challenging because of overlaps in the diagnostic features, leading to considerable interobserver variability. To provide an overview of the diagnostic agreement for lung adenocarcinoma subtypes among pathologists and to create a ground truth using the clustering approach for downstream computational applications. Three sets of lung adenocarcinoma histologic images with different evaluation levels (small patches, areas with relatively uniform histology, and whole slide images) were reviewed by 17 international expert lung pathologists and 1 pathologist in training. Each image was classified into one or several lung adenocarcinoma subtypes. Among the 4702 patches of the first set, 1742 (37%) had an overall consensus among all pathologists. The overall Fleiss κ score for the agreement of all subtypes was 0.58. Using cluster analysis, pathologists were hierarchically grouped into 2 clusters, with κ scores of 0.588 and 0.563 in clusters 1 and 2, respectively. Similar results were obtained for the second and third sets, with fair-to-moderate agreements. Patches from the first 2 sets that obtained the consensus of the 18 pathologists were retrieved to form consensus patches and were regarded as the ground truth of lung adenocarcinoma subtypes. Our observations highlight discrepancies among experts when assessing lung adenocarcinoma subtypes. However, a subsequent number of consensus patches could be retrieved from each cluster, which can be used as ground truth for the downstream computational pathology applications, with minimal influence from interobserver variability.

Several reports have shown that statin treatment benefits patients with asthma; however, inconsistent effects have been observed. The mir-152 family (148a, 148b and 152) has been implicated in asthma. These microRNAs suppress HLA-G expression, and rs1063320, a common SNP in the HLA-G 3′UTR that is associated with asthma risk, modulates miRNA binding. We report that statins upregulate mir-148b and 152, and affect HLA-G expression in an rs1063320-dependent fashion. In addition, we found that individuals who carried the G minor allele of rs1063320 had reduced asthma-related exacerbations (emergency department visits, hospitalizations or oral steroid use) compared with non-carriers ( P =0.03) in statin users ascertained in the Personalized Medicine Research Project at the Marshfield Clinic ( n =421). These findings support the hypothesis that rs1063320 modifies the effect of statin benefit in asthma, and thus may contribute to variation in statin efficacy for the management of this disease.