To map, within a single integrated framework, the full spectrum of desirable (‘feel-good’) and less desirable (‘feel-bad’) psychological outcomes and mental health trajectories after metabolic and bariatric surgery (MBS), and to identify the knowledge gaps that emerge only when both sides are viewed together. Across 251 included studies, the desirable arm comprised four interconnected domains: improved mental health (depression, anxiety, mood, eating disorders); enhanced physical-health domains supporting psychological well-being; improved body image, self-esteem and relational functioning; and gains in occupational, educational and economic participation. The less desirable arm comprised three themes: a spectrum of adverse outcomes; the negotiation of self and existential tensions; and a ‘lonely struggle’ against insufficient support, encompassing the most serious outcomes of suicide, self-harm and alcohol-use disorder. Thirty-seven studies contributed to both arms, and benefits and burdens frequently coexisted within the same patient over time. Recent studies show that these gains are smaller and less durable than group averages suggest. Improvements in depressive and anxiety symptoms are largest in the first year and smaller thereafter or partly reversed; symptoms persist or worsen in a subset of patients; relationship, work, body-image, and weight-stigma outcomes run in both directions; and the benefits differ by sex, ethnicity, age group, and pre-surgical psychiatric history. The psychological aftermath of MBS is a dual reality rather than a uniformly positive or negative one. Reframing psychological success as the net balance between the two trajectories supports biopsychosocial, multidisciplinary, long-term care, and points to a research agenda built on within-cohort, dual-outcome longitudinal designs. This is the first scoping review to map the full spectrum of both desirable and less desirable psychological outcomes after MBS within a single integrated framework, rather than treating the two sides in isolation. Desirable trajectories span mental, physical, psychological/intrapersonal, and social/occupational domains; less desirable trajectories span adverse outcomes, self and existential tensions, and a ‘lonely struggle’ against insufficient support. Both arms are defined by the direction an outcome moved in, so the same domains can appear on each side; the gains are typical rather than universal and can fade with time. Suicide, self-harm, and alcohol use disorder are consistent but under-characterized post-MBS risks; this review consolidates and strengthens the evidence for these severe outcomes. Psychological success after MBS is best understood as the net balance of ‘feel-good’ and ‘feel-bad’ trajectories, supporting integrated, multidisciplinary, lifelong psychosocial care.
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent one of the most significant therapeutic advances in the management of type 2 diabetes and obesity. As their indications have expanded to include cardiovascular and kidney disease, safety concerns involving multiple organ systems have received increasing attention. This narrative review examines the spectrum of adverse effects linked to GLP-1RAs and provides a clinically relevant platform for assessing their safe prescription. Gastrointestinal intolerance, modest increases in heart rate, and a modest but reproducible increase in the risk of gallbladder and biliary disease represent the most consistently supported adverse effects of GLP-1RAs. A risk of pancreatitis is also considered to exist, although some studies have challenged this association. Conversely, correlations with neuropsychiatric and dermatological disorders, diabetic retinopathy, nonarteritic anterior ischemic optic neuropathy, perioperative aspiration, sexual and reproductive disturbances, sarcopenia, and malignancy remain controversial. Most available evidence derives from pharmacovigilance databases, retrospective observational studies, and secondary analyses of randomized trials, which are limited by reporting bias, residual confounding, and inability to establish causality. Heterogeneity in study design, statistical methodology, outcome definitions, and patient populations further complicates interpretation. Although several proposed adverse effects have biologically plausible mechanisms, prospective clinical validation remains limited. Notably, recent regulatory decisions, including the Food and Drug Administration (FDA)’s removal of the suicidality warning from GLP-1RA prescribing information, reflect the evolving nature of these safety assessments. The overall benefit–risk profile of GLP-1RAs is favorable. Most emerging safety concerns should currently be regarded as hypothesis-generating signals rather than established toxicities. Individualized risk assessment and appropriate clinical monitoring remain important as ongoing and future prospective studies further define the long-term safety of this rapidly expanding therapeutic class.
Obesity is an established risk factor for postmenopausal hormone receptor–positive breast cancer, largely through estrogen-mediated pathways. Emerging evidence suggests that obesity-related metabolic dysfunction may also contribute to the risk and aggressive biology of receptor-negative breast cancer, particularly TNBC, among premenopausal women and populations undergoing rapid metabolic transition. This review evaluates epidemiologic, mechanistic, and translational evidence linking metabolic dysfunction to TNBC. Observational studies and pooled analyses report modest but reproducible associations between adiposity and TNBC, stronger in some metabolically high-risk populations but heterogeneous across studies. BMI-based Mendelian randomization generally yields inverse associations with overall breast cancer, whereas bariatric-surgery studies suggest lower overall incidence without establishing TNBC-specific effects. These discordant causal-inference findings do not demonstrate that obesity directly causes TNBC. Mechanistic studies indicate that adipose inflammation, adipokine imbalance, insulin/IGF-1 signaling, and immune remodeling can promote inflammatory signaling, metabolic adaptation, and epithelial plasticity. These processes support biologic plausibility but do not demonstrate de novo conversion to a receptor-negative subtype in vivo. Current evidence supports a model in which obesity-related metabolic dysfunction may create a breast microenvironment favoring tumor-promoting inflammation and aggressive features associated with TNBC. Priorities include refined metabolic phenotyping, biomarker-driven risk stratification, validation in human-relevant models, and biomarker-enriched feasibility studies testing whether modifying metabolic dysfunction alters intermediate metabolic or tissue endpoints. An evidence-graded framework is needed to distinguish association, biologic plausibility, and causal inference.
We synthesize recent developments across two linked literatures, ultra-processed foods (UPFs) and the construct of UPF addiction, engaging contested questions of health harm, classification, assessment, and recognition. Advances include: 1) feeding trials and diet-quality-adjusted cohorts indicating harm from processing itself; 2) analyses linking critiques of UPF classification predominantly to industry-affiliated authors; 3) findings consistent with the addictive-substance hypothesis: GLP-1 agonists reduce UPF intake and addictive-substance use, and analyses identify UPF attributes driving addictive-like eating; 4) the first clinician-administered UPF addiction interview extends assessment beyond self-report; and 5) Delphi consensus and regulatory and legislative attention signaling recognition of UPF addiction. Evidence increasingly supports treating UPFs and UPF addiction as one problem, the substance and the disorder, reshaping research and policy priorities. The evidence base for recognition rivals that of some recognized disorders, though its sufficiency remains debated. Gaps include targeted interventions and clinician-administered assessment data.
This review evaluates obesity as the organizing exposure linking mechanical loading and adipose-tissue dysfunction with tendon pathology. It synthesizes site- and outcome-specific human evidence, candidate mechanisms, tendon xanthomas associated with familial hypercholesterolemia (FH), and implications for targeted assessment and management. Human studies associate obesity and related cardiometabolic abnormalities with tendinopathy, tendon rupture, and postoperative outcomes, but findings vary by exposure, site, and outcome and remain predominantly observational. Limited human tissue and predominantly preclinical studies support candidate roles for glycation, oxidized lipids, chronic inflammation, mitochondrial and redox dysfunction, and impaired repair, although their causal sequence and human relevance remain uncertain. Recent single-cell and spatial studies reveal tendon cellular heterogeneity but have not established obesity- or metabolism-specific endotypes. Recurrent, bilateral, atraumatic, or treatment-resistant manifestations have been proposed as features of a hypothesis-generating “metabolic tendon phenotype” rather than a validated diagnostic entity. FH-related tendon xanthomas represent a distinct manifestation of severe cumulative low-density lipoprotein cholesterol exposure. Standard tendon-directed rehabilitation remains central, whereas tendon-specific benefits of cardiometabolic optimization, glucagon-like peptide-1 receptor agonists, bariatric surgery, or lipid-lowering therapy remain unconfirmed. The proposed mechanometabolic continuum integrates obesity-associated systemic influences with local loading as a conceptual framework rather than a validated disease model or screening tool. Current evidence does not support universal cardiometabolic or cardiovascular screening based on nonspecific tendinopathy alone; targeted assessment may be considered in selected patients with relevant clinical cues or conventional risk factors. Longitudinal human studies and intervention trials are needed to clarify causality and clinical utility.
