Developing a large-scale quality improvement program for thyroid cancer surgery.

BACKGROUND: Surgical quality improvement (QI) plays a critical role in optimizing patient outcomes and reducing healthcare costs. QI programs focusing specifically on thyroid cancer surgical care are lacking. This study aimed to (a) select and introduce surgical quality indicators for thyroid cancer and (b) identify areas for QI at the state-level. METHODS: A multidisciplinary team of thyroid cancer and QI experts selected 10 thyroid cancer-specific quality indicators and assessed the quality of thyroid cancer surgical care compared to current national guidelines. Analysis of the first year (January-December 2023) of data collection was performed using descriptive statistics. RESULTS: The thyroid cancer quality indicators included preoperative cytology, postoperative pathology, staging, cancer size, margin status, extrathyroidal extension, lymph nodes, postoperative complications within 30 days, documented follow-up treatment, and documented surveillance plans. 112 surgeons performed 360 thyroidectomies for thyroid cancer at 51 hospitals. Preoperative cytology was not performed in 34.3% (n = 103) of cases with thyroid cancer on final pathology. When the extent of surgery was evaluated by papillary cancer size, 50.0% (n = 38) of patients with <1 cm cancers underwent total thyroidectomy, and 13.8% (n = 4) with >4 cm underwent thyroid lobectomy. Positive margins were found in 16.2% (n = 53). Postoperatively, 19.2% (n = 69) of patients lacked documented follow-up, and 18.6% (n = 67) lacked thyroid cancer surveillance plans. CONCLUSIONS: Establishing a dedicated QI program for thyroid cancer provides a previously unharnessed opportunity to enhance the quality of thyroid cancer surgical care. Statewide surgical quality collaboratives offer a model for establishing thyroid cancer QI initiatives across diverse healthcare settings in other states and countries.

Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®.

Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa®, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi®, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.

An rhs gene of Pseudomonas aeruginosa encodes a virulence protein that activates the inflammasome.

The rhs genes are a family of enigmatic composite genes, widespread among Gram-negative bacteria. In this study, we characterized rhsT, a Pseudomonas aeruginosa rhs gene that encodes a toxic protein. Expression of rhsT was induced upon contact with phagocytic cells. The RhsT protein was exposed on the bacterial surface and translocated into phagocytic cells; these cells subsequently underwent inflammasome-mediated death. Moreover, RhsT enhanced host secretion of the potent proinflammatory cytokines IL-1ß and IL-18 in an inflammasome-dependent manner. In a mouse model of acute pneumonia, infection with a P. aeruginosa strain lacking rhsT was associated with less IL-18 production, fewer recruited leukocytes, reduced pulmonary bacterial load, and enhanced animal survival. Thus, rhsT encodes a virulence determinant that activates the inflammasome.

Defective gut function in drop-dead mutant Drosophila.

Mutation of the gene drop-dead (drd) causes adult Drosophila to die within 2 weeks of eclosion and is associated with reduced rates of defecation and increased volumes of crop contents. In the current study, we demonstrate that flies carrying the strong allele drd(lwf) display a reduction in the transfer of ingested food from the crop to the midgut, as measured both as a change in the steady-state distribution of food within the gut and also in the rates of crop emptying and midgut filling following a single meal. Mutant flies have abnormal triglyceride (TG) and glycogen stores over the first 4 days post-eclosion, consistent with their inability to move food into the midgut for digestion and nutrient absorption. However, the lifespan of mutants was dependent upon food presence and quality, suggesting that at least some individual flies were able to digest some food. Finally, spontaneous motility of the crop was abnormal in drd(lwf) flies, with the crops of mutant flies contracting significantly more rapidly than those of heterozygous controls. We therefore hypothesize that mutation of drd causes a structural or regulatory defect that inhibits the entry of food into the midgut.