Severe Lung Injury Associated With Use of e-Cigarette, or Vaping, Products-California, 2019.

Importance: Since August 2019, more than 2700 patients have been hospitalized with e-cigarette, or vaping, product use-associated lung injury (EVALI) across the United States. This report describes the outbreak in California, a state with one of the highest case counts and with a legal adult-use (recreational) cannabis market. Objective: To present clinical characteristics and vaping product exposures of patients with EVALI in California. Design, Setting, and Participants: Case series describing epidemiologic and laboratory data from 160 hospitalized patients with EVALI reported to the California Department of Public Health by local health departments, who received reports from treating clinicians, from August 7 through November 8, 2019. Exposures: Standardized patient interviews were conducted to assess vaping products used, frequency of use, and method of product acquisition. Vaping products provided by a subset of patients were tested for active ingredients and other substances. Main Outcomes and Measures: Demographic and clinical characteristics, level of care, and outcomes of hospitalization were obtained from medical record review. Results: Among 160 patients with EVALI, 99 (62%) were male, and the median age was 27 years (range, 14-70 years). Of 156 patients with data available, 71 (46%) were admitted to an intensive care unit, and 46 (29%) required mechanical ventilation. Four in-hospital deaths occurred. Of 86 patients interviewed, 71 (83%) reported vaping tetrahydrocannabinol (THC)-containing products, 36 (43%) cannabidiol (CBD)-containing products, and 39 (47%) nicotine-containing products. Sixty-five of 87 (75%) THC-containing products were reported as obtained from informal sources, such as friends, acquaintances, or unlicensed retailers. Of 87 vaping products tested from 24 patients, 49 (56%) contained THC. Vitamin E or vitamin E acetate was found in 41 (84%) of the THC-containing products and no nicotine products. Conclusions and Relevance: Patients' clinical outcomes and vaping behaviors, including predominant use of THC-containing products from informal sources, are similar to those reported by other states, despite California's legal recreational cannabis market. While most THC products tested contained vitamin E or vitamin E acetate, other underlying cause(s) of injury remain possible. The California Department of Public Health recommends that individuals refrain from using any vaping or e-cigarette products, particularly THC-containing products from informal sources, while this investigation is ongoing.

Notes from the Field: Investigation of Hepatitis C Virus Transmission Associated with Injection Therapy for Chronic Pain - California, 2015.

On November 26, 2014, the California Department of Public Health (CDPH) contacted CDC concerning a report from the Santa Barbara County Public Health Department (SBPHD) regarding acute hepatitis C virus (HCV) infection in a repeat blood donor. The patient, who was asymptomatic, was first alerted of the infection by the blood bank and had no traditional risk factors for HCV infection. The donor had a negative HCV nucleic acid test (NAT) 56 days before the first positive NAT test, and an investigation into the donor's health care exposures and other potential risk factors, including injection drug use, incarceration, and long-term hemodialysis within this narrow exposure window, was conducted by SBPHD.

Synthesis and biological evaluation of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of cyclin-dependent kinases.

Using a high-throughput screening strategy, a series of 1-aryl-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4-ones was identified that inhibit the cyclin-dependent kinase (CDK) 4/cyclin D1 complex-mediated phosphorylation of a protein substrate with IC(50)s in the low micromolar range. On the basis of preliminary structure-activity relationships (SAR), a model was proposed in which these inhibitors occupy the ATP-binding site of the enzyme, forming critical hydrogen bonds to the same residue (Val96) to which the amino group in ATP is presumed to bind. X-ray diffraction studies on a later derivative bound to CDK2 support this binding mode. Iterative cycles of synthesis and screening lead to a novel series of potent, CDK2-selective 6-(arylmethyl)pyrazolopyrimidinones. Placement of a hydrogen-bond donor in the meta-position on the 6-arylmethyl group resulted in approximately 100-fold increases in CDK4 affinity, giving ligands that were equipotent inhibitors of CDK4 and CDK2. These compounds exhibit antiproliferative effects in the NCI HCT116 and other cell lines. The potency of these antiproliferative effects is enhanced in anilide derivatives and translates into tumor growth inhibition in a mouse xenograft model.