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Aims Methods Results Conclusions The SURMOUNT‐1 trial investigated effects of tirzepatide, a glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 receptor agonist, on body weight in participants with obesity or overweight. This analysis evaluated changes in patient‐reported outcomes (PROs) assessing physical function, psychosocial well‐being, and overall health aspects of participants' health‐related quality of life (HRQoL) in SURMOUNT‐1.PRO instruments included the Impact of Weight on Quality of Life‐Lite Clinical Trials version (IWQOL‐Lite‐CT), Short Form Survey‐36 version 2 (SF‐36v2) and EQ‐5D‐5L. Scores were analysed by treatment group and by categorical degree of weight reduction group: >0 to <5%, ≥5 to <10%, ≥10 to <20% and ≥20%. Relevant PROs were evaluated for participants with or without physical or psychosocial limitations at baseline, as measured by Patient Global Impression of Status for physical activity (PGIS) and Patient Health Questionnaire‐2 (PHQ‐2), respectively.All tirzepatide groups demonstrated significant improvements in PRO scores versus placebo. There was a consistent trend of incremental PRO improvement with greater degrees of weight reduction, starting from ≥5% weight reduction. Participants achieving ≥20% weight reduction demonstrated the greatest changes from baseline to week 72 (SF‐36v2 Physical Component Summary, 4.60; SF‐36v2 Mental Component Summary, 0.80; IWQOL‐Lite CT Total score, 24.7). Those with baseline physical and psychosocial limitations experienced greater improvements than those without.Tirzepatide treatment was associated with improved HRQoL compared to placebo in people with overweight or obesity. Higher percentages of weight reduction were associated with greater improvements.Clinical trial registration number for SURMOUNT‐1: NCT04184622. [ABSTRACT FROM AUTHOR]

The multinational CRASH study found that substantive recommendations from health care providers were predictive of actions taken by people with diabetes during and after a severe hypoglycemic event, which highlights the importance of equipping people with actionable strategies to prevent and treat severe hypoglycemia should a severe hypoglycemic event arise., (© 2022 Eli Lilly and Company.)

Engulfment of IgG-coated particles by neutrophils and macrophages is an essential component of the innate immune response. This process, known as phagocytosis, is triggered by clustering of FcgammaR at sites where leukocytes make contact with the opsonized particles. We found that phagocytosis is accompanied by a burst of fluid phase pinocytosis, which is largely restricted to the immediate vicinity of the phagosomal cup. FcgammaR-induced pinocytosis preceded and appeared to be independent of phagosomal sealing. Accordingly, fluid phase uptake was accentuated by actin depolymerization, which precludes phagocytosis. Stimulation of pinocytosis required phosphatidylinositol 3-kinase activity and was eliminated when changes in the cytosolic free Ca(2+) concentration were prevented. Because stimulation of FcgammaR also induces secretion, which is similarly calcium and phosphatidylinositol 3-kinase dependent, we studied the possible relationship between these events. Neutrophil fragments devoid of secretory granules (cytoplasts) were prepared by sedimentation through Ficoll gradients. Cytoplasts could perform FcgammaR-mediated phagocytosis, which was not accompanied by activation of pinocytosis. This observation suggests that granule exocytosis is required for stimulation of pinocytosis. Analysis of the cytosolic Ca(2+) dependence of secretion and pinocytosis suggests that primary (lysosomal) granule exocytosis is the main determinant of pinocytosis during FcgammaR stimulation. Importantly, primary granules are secreted in a polarized fashion near forming phagosomes. Focal pinocytosis during particle engulfment may contribute to Ag processing and presentation and/or to retrieval of components of the secretory machinery. Alternatively, it may represent an early event in the remodeling of the phagosomal membrane, leading to phagosomal maturation.