Abstract
Background
Fentanyl was developed in the 1960s as an alternative to morphine, but quickly became a drug of abuse due to its potency, inexpensiveness, and ease of synthesis. One source of ...exposure is mixing fentanyl into other drugs of abuse (e.g., heroin), but users also actively seek out this potent opioid. While monitoring for pain medication compliance and office-based opioid treatment, we noticed increasing fentanyl use. We sought to investigate this increase in the local population, and see if this reflected the regional health, morbidity, and mortality statistics.
Methods
This data review was determined not to involve “human subjects” as defined by federal regulations by the University of Washington (UW) Human Subjects Division (STUDY00014988). Local data were extracted from the laboratory information system and analyzed. Data from the King County Medical Examiner’s Office derives from cases sent to the Washington State Toxicology Laboratory. The Addictions, Drug, and Alcohol Institute (ADAI) at the UW compiled data from the Washington State Department of Health, the Forensic Laboratory Services Bureau, Washington State Patrol, and the state Office of Financial Management.
Results
We found a significant increase in fentanyl positivity in clinical LC-MS/MS assays, an increase in deaths due to fentanyl, and an increase in the fentanyl usage documented by the public health laboratory.
Conclusions
Clinical data from community toxicology testing performed at academic medical centers can reflect trends in society at large, and as such, there may be a compelling reason to publish and use these data to inform public health approaches.
IMPORTANCE: Drug overdose (OD) is a public health challenge and an important cause of out-of-hospital cardiac arrest (OHCA). Existing studies evaluating OD-related OHCA (OD-OHCA) either aggregate all ...drugs or focus on opioids. The epidemiology, presentation, and outcomes of drug-specific OHCA are largely unknown. OBJECTIVE: To evaluate the temporal pattern, clinical presentation, care, and outcomes of adult patients with OHCA overall and according to the drug-specific profile. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of adults with OHCA in King County Washington was conducted between January 1, 2015, and December 31, 2021. Etiology of OHCA was determined using emergency medical service, hospital, and medical examiner records. Etiology was classified as non-OD OHCA or OD-OHCA, with drug-specific profiles categorized as (1) opioid without stimulant, (2) stimulant without opioid, (3) opioid and stimulant, or (4) all other nonstimulant, nonopioid drugs. Statistical analysis was performed on July 1, 2023. EXPOSURE: Out-of-hospital cardiac arrest. MAIN OUTCOMES AND MEASURES: The primary outcome was survival to hospital discharge. The secondary outcome was survival with favorable functional status defined by Cerebral Performance Category 1 or 2 based on review of the hospital record. RESULTS: In this cohort study, there were 6790 adult patients with emergency medical services–treated OHCA from a US metropolitan system. During the 7-year study period, there were 702 patients with OD-OHCA (median age, 41 years IQR, 29-53 years; 64% male n = 450 and 36% female n = 252) and 6088 patients with non-OD OHCA (median age, 66 years IQR, 56-77 years; 65% male n = 3944 and 35% female n = 2144). The incidence of OD-OHCA increased from 5.2 (95% CI, 3.8-6.6) per 100 000 person-years in 2015 to 13.0 (95% CI, 10.9-15.1) per 100 000 person-years in 2021 (P < .001 for trend), whereas there was no significant temporal change in the incidence of non-OD OHCA (P = .30). OD-OHCA were more likely to be unwitnessed (66% 460 of 702 vs 41% 2515 of 6088) and less likely to be shockable (8% 56 of 702 vs 25% 1529 of 6088) compared with non-OD OHCA. Unadjusted survival was not different (20% 138 of 702 for OD vs 18% 1095 of 6088 for non-OD). When stratified by drug profile, combined opioid-stimulant OHCA demonstrated the greatest relative increase in incidence. Presentation and outcomes differed by drug profile. Patients with stimulant-only OHCA were more likely to have a shockable rhythm (24% 31 of 129) compared with patients with opioid-only OHCA (4% 11 of 295) or patients with combined stimulant-opioid OHCA 5% 10 of 205), and they were more likely to have a witnessed arrest (50% 64 of 129) compared with patients with OHCA due to other drugs (19% 14 of 73) or patients with combined stimulant-opioid OHCA (23% 48 of 205). Patients with a combined opioid-stimulant OHCA had the lowest survival to hospital discharge (10% 21 of 205) compared with patients with stimulant-only OHCA (22% 29 of 129) or patients with OHCA due to other drugs (26% 19 of 73), a difference that persisted after multivariable adjustment. CONCLUSIONS AND RELEVANCE: In a population-based cohort study, the incidence of OD-OHCA increased significantly from 2015 to 2021, with the greatest increase observed among patients with a combined stimulant-opioid OHCA. Presentation and outcome differed according to the drug-specific profile. The combination of increasing incidence and lower survival among among patients with a opioid-stimulant OHCA supports prevention and treatment initiatives that consider the drug-specific profile.
Local immune activation at mucosal surfaces, mediated by mucosal lymphoid tissues, is vital for effective immune responses against pathogens. While pathogens like severe acute respiratory syndrome ...coronavirus 2 (SARS-CoV-2) can spread to multiple organs, patients with coronavirus disease 2019 (COVID-19) primarily experience inflammation and damage in their lungs. To investigate this apparent organ-specific immune response, we develop an analytical framework that recognizes the significance of mucosal lymphoid tissues. This framework combines histology, immunofluorescence, spatial transcript profiling, and mathematical modeling to identify cellular and gene expression differences between the lymphoid tissues of the lung and the gut and predict the determinants of those differences. Our findings indicate that mucosal lymphoid tissues are pivotal in organ-specific immune response to SARS-CoV-2, mediating local inflammation and tissue damage and contributing to immune dysfunction. The framework developed here has potential utility in the study of long COVID and may streamline biomarker discovery and treatment design for diseases with differential pathologies at the organ level.
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•Mucosal lymphoid tissues drive organ-specific response during SARS-CoV-2 infection•Injury signature is enriched in the lymphoid tissues of the lung relative to the gut•Lung lymphoid tissues harbor increased inflammatory macrophages during infection•Absence of activated dendritic cells in those tissues suggests immune dysfunction
Ng et al. investigate the role of mucosal lymphoid tissues in SARS-CoV-2 infection, uncovering distinct immune responses in the lung versus the gut. Lung lymphoid tissues exhibit elevated inflammatory macrophages, diminished activated dendritic cells, and amplified injury signatures, underscoring their pivotal role in organ-specific infection response.
Traumatic cardiac ventricular ruptures in children are rare. Only a single case of left ventricular rupture due to child abuse has been reported. We report a child who sustained a fatal left ...ventricular apical rupture. It appeared to have resulted from hydrostatic forces resulting from abusive blunt thoracic injury. That he was being abused was previously missed when he was presented to the emergency department with facial pyoderma. It was not noted that he also had lip and oral mucosal injury, sites not affected by staph toxins. As a result, his underlying, abusive and secondarily infected, facial flow type scald burn was not appreciated. Within a week thereafter his fatal injury occurred, accompanied by extensive and obvious associated abusive injuries. Postmortem high‐detail whole body computed tomography scanning aided the autopsy. Although rare, ventricular rupture from abusive blunt thoracic injury can occur.
The androgen receptor (AR) is strongly expressed in the majority of breast carcinomas, but its role in breast hormonal carcinogenesis is not clear. We believe a better knowledge of the biology of ...normal/benign breast tissue will be the key to understanding this process. Using standard immunohistochemical staining on consecutive sections and dual immunohistochemical labeling, we studied the expression pattern of AR and estrogen receptor (ER) in normal/benign breast luminal epithelial cells. We found that most of the AR-positive cells are also ER positive, about 10% of the cells are AR-positive only, whereas ER-positive only cells are uncommon, a distribution pattern of hormone receptor expression similar to what was revealed in invasive breast carcinomas. Whereas the expression of AR downstream proteins, such as prostate-specific antigen and gross cystic disease fluid protein, was either negative or unrelated to the AR status. We conclude that AR and ER expression status in invasive breast carcinomas reflects that of their progenitor cells in terminal duct lobular units. Our study did not reveal the expression of AR downstream proteins in normal/benign luminal epithelial cells at the regular immunohistochemistry level.
Traumatic cardiac ventricular ruptures in children are rare. Only a single case of left ventricular rupture due to child abuse has been reported. We report a child who sustained a fatal left ...ventricular apical rupture. It appeared to have resulted from hydrostatic forces resulting from abusive blunt thoracic injury. That he was being abused was previously missed when he was presented to the emergency department with facial pyoderma. It was not noted that he also had lip and oral mucosal injury, sites not affected by staph toxins. As a result, his underlying, abusive and secondarily infected, facial flow type scald burn was not appreciated. Within a week thereafter his fatal injury occurred, accompanied by extensive and obvious associated abusive injuries. Postmortem high-detail whole body computed tomography scanning aided the autopsy. Although rare, ventricular rupture from abusive blunt thoracic injury can occur.
