In Vivo, In Vitro and In Silico Anticancer Activity of Ilama Leaves: An Edible and Medicinal Plant in Mexico.

Ilama leaves are an important source of secondary metabolites with promising anticancer properties. Cancer is a disease that affects a great number of people worldwide. This work aimed to investigate the in vivo, in vitro and in silico anticancer properties of three acyclic terpenoids (geranylgeraniol, phytol and farnesyl acetate) isolated from petroleum ether extract of ilama leaves. Their cytotoxic activity against U-937 cells was assessed using flow cytometry to determine the type of cell death and production of reactive oxygen species (ROS). Also, a morphological analysis of the lymph nodes and a molecular docking study using three proteins related with cancer as targets, namely, Bcl-2, Mcl-1 and VEGFR-2, were performed. The flow cytometry and histomorphological analysis revealed that geranylgeraniol, phytol and farnesyl acetate induced the death of U-937 cells by late apoptosis and necrosis. Geranylgeraniol and phytol induced a significant increase in ROS production. The molecular docking studies showed that geranylgeraniol had more affinity for Bcl-2 and VEGFR-2. In the case of farnesyl acetate, it showed the best affinity for Mcl-1. This study provides information that supports the anticancer potential of geranylgeraniol, phytol and farnesyl acetate as compounds for the treatment of cancer, particularly with the potential to treat non-Hodgkin's lymphoma.

Markov models for clinical decision-making in radiation oncology: A systematic review.

The intrinsic stochasticity of patients' response to treatment is a major consideration for clinical decision-making in radiation therapy. Markov models are powerful tools to capture this stochasticity and render effective treatment decisions. This paper provides an overview of the Markov models for clinical decision analysis in radiation oncology. A comprehensive literature search was conducted within MEDLINE using PubMed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only studies published from 2000 to 2023 were considered. Selected publications were summarized in two categories: (i) studies that compare two (or more) fixed treatment policies using Monte Carlo simulation and (ii) studies that seek an optimal treatment policy through Markov Decision Processes (MDPs). Relevant to the scope of this study, 61 publications were selected for detailed review. The majority of these publications (n = 56) focused on comparative analysis of two or more fixed treatment policies using Monte Carlo simulation. Classifications based on cancer site, utility measures and the type of sensitivity analysis are presented. Five publications considered MDPs with the aim of computing an optimal treatment policy; a detailed statement of the analysis and results is provided for each work. As an extension of Markov model-based simulation analysis, MDP offers a flexible framework to identify an optimal treatment policy among a possibly large set of treatment policies. However, the applications of MDPs to oncological decision-making have been understudied, and the full capacity of this framework to render complex optimal treatment decisions warrants further consideration.

Categorizing temporomandibular joint arthroscopic procedures for a better clinical practice and teaching.

OBJECTIVE: To provide some clarity to the confusion in the terminology used to classify arthroscopic procedures for the treatment of temporomandibular joint (TMJ) internal derangement (ID) and osteoarthrosis (OA). MATERIAL AND METHODS: The author introduces a new method for categorizing TMJ arthroscopic procedures more accurately, intending to establish a reference point from which further clinical series may built their analyses. RESULTS: Six categories are proposed for establishing a clear distinction among performed arthroscopic procedures: Level Ia, arthroscopic lavage (AL); Level Ib, arthroscopic lysis and lavage (ALL); Level Ic, ALL "needle-therapy"; Level IIa, simple operative arthroscopy (OA); Level IIb, advanced OA; and Level III, OA with discopexy. Several arthroscopic procedures, such as lysis of adherences, coblation of the retrodiscal tissue, anterior myotomy of the lateral pterigoid muscle, or discopexy, are classified in each category depending on the need (or not) to use of one or two working cannulas. CONCLUSION: Teaching and training of maxillofacial surgeons in the acquisition of the skills to perform arthroscopy should be based on a step-by-step approach following this proposed classification. Besides, future clinical series on arthroscopy of the TMJ for the treatment of ID and/or osteoarthrosis may benefit from a clear distinction of the performed arthroscopic procedure in terms of evaluating outcomes and complications.

Impact of an Evidence-Based Prioritization System and Electronic Consultation in Early Diagnosis of Colorectal Cancer.

(1) Background: Colorectal cancer (CRC) is one of the most common causes of cancer. Timely diagnosis is critical, with even minor delays impacting prognosis. Primary care providers face obstacles in accessing specialist care. This study investigates the impact of implementing an electronic consultation (eConsult) system combined with a specific prioritization system on CRC diagnosis delay and tumor staging. (2) Methods: The study analyzes 245 CRC patients from November 2019 to February 2022, comparing those referred before and after the eConsult system's implementation during the COVID-19 pandemic. Data on referral reasons, pathways, diagnosis delays, and staging were collected. Multivariate analysis aimed to identify independent risk factors for advanced staging at diagnosis. (3) Results: The eConsult system significantly reduced CRC diagnosis delay from 68 to 26 days. The majority of patients referred via eConsult presented with symptoms. Despite expedited diagnoses, no discernible difference in CRC staging emerged between eConsult and traditional referrals. Notably, patients from screening programs or with a positive fecal immunochemical test (FIT) experienced earlier-stage diagnoses. A positive FIT without symptoms and being a never-smoker emerged as protective factors against advanced-stage CRC. (4) Conclusions: This study highlights eConsult's role in reducing CRC diagnosis delay, improving diagnostic efficiency and prioritizing urgent cases, emphasizing FIT effectiveness.

Risk factors for massive gastrointestinal bleeding occurrence and mortality: A prospective single-center study.

BACKGROUND: Massive gastrointestinal bleeding is a life-threatening condition without a well-established definition. We aimed to analyze the characteristics, risk factors, and outcomes of patients with massive upper gastrointestinal bleeding. METHODS: Our study analyzed a prospective registry of patients admitted between 2013 and 2020 with variceal and non-variceal causes. Severe bleeding was defined as ongoing bleeding requiring transfusion of more than 2 units of packed red blood cells within 24 hours, accompanied by signs of shock. The main outcomes were 30-day and 6-month mortality, rebleeding within 7 days, persistent bleeding, and severe complications during admission. RESULTS: Out of 1213 patients, 171 had massive gastrointestinal bleeding, with a predominance of males. The massive bleeding group had higher rates of chronic kidney disease, cirrhosis, in-patient status, disseminated malignancy, alcoholism, and ASA score ≥3. All major outcomes, including 30-day mortality, 6-month mortality, rebleeding, persistent bleeding, and severe complications, were more common in the massive bleeding group. Multivariate logistic regression identified inpatient status, systemic diseases, malignancy, active bleeding in endoscopy, and severe complications as risk factors for massive bleeding and mortality. CONCLUSIONS: Inpatient status and comorbidities, especially systemic diseases, and malignancies, were associated with a higher risk of massive bleeding. Mortality was linked to chronic kidney disease, cirrhosis, severe comorbidities, and alcohol consumption. We observed increased 6-months mortality, probably related to a health status in which gastrointestinal bleeding heralded poor outcomes, some of them potentially preventable. Innovative healthcare interventions, such as Emergency Department-based intermediate care areas or Intensive Care Units, and multidisciplinary follow-up, could potentially improve survival.

Interatrial Septum Stenting for Hypoplastic Left Heart Syndrome in Ex Utero Intrapartum Therapy.

Patients with hypoplastic left heart syndrome (HLHS) with intact atrial septum have an increased mortality rate. This presentation occurs in 6% to 10% of cases. We present a patient with fetal diagnosis of HLHS with restrictive atrial septum. We performed a cesarean section at 37 weeks of gestation, and under ex utero intrapartum treatment proceeded with a median sternotomy and transatrial stenting for left atrial decompression due to findings of intact atrial septum on the fetal echocardiogram performed during the procedure. Subsequently, the patient underwent hybrid stage I palliation followed by a comprehensive stage II procedure at five months of age, but unfortunately died from postoperative complications.

ERG potassium channels and T-type calcium channels contribute to the pacemaker and atrioventricular conduction in zebrafish larvae.

AIM: Bradyarrhythmias result from inhibition of automaticity, prolonged repolarization, or slow conduction in the heart. The ERG channels mediate the repolarizing current IKr in the cardiac action potential, whereas T-type calcium channels (TTCC) are involved in the sinoatrial pacemaker and atrioventricular conduction in mammals. Zebrafish have become a valuable research model for human cardiac electrophysiology and disease. Here, we investigate the contribution of ERG channels and TTCCs to the pacemaker and atrioventricular conduction in zebrafish larvae and determine the mechanisms causing atrioventricular block. METHODS: Zebrafish larvae expressing ratiometric fluorescent Ca2+ biosensors in the heart were used to measure Ca2+ levels and rhythm in beating hearts in vivo, concurrently with contraction and hemodynamics. The atrioventricular delay (the time between the start of atrial and ventricular Ca2+ transients) was used to measure impulse conduction velocity and distinguished between slow conduction and prolonged refractoriness as the cause of the conduction block. RESULTS: ERG blockers caused bradycardia and atrioventricular block by prolonging the refractory period in the atrioventricular canal and in working ventricular myocytes. In contrast, inhibition of TTCCs caused bradycardia and second-degree block (Mobitz type I) by slowing atrioventricular conduction. TTCC block did not affect ventricular contractility, despite being highly expressed in cardiomyocytes. Concomitant measurement of Ca2+ levels and ventricular size showed mechano-mechanical coupling: increased preload resulted in a stronger heart contraction in vivo. CONCLUSION: ERG channels and TTCCs influence the heart rate and atrioventricular conduction in zebrafish larvae. The zebrafish lines expressing Ca2+ biosensors in the heart allow us to investigate physiological feedback mechanisms and complex arrhythmias.

Kidney function in patients with adrenal adenomas: A single-center retrospective cohort study.

OBJECTIVE: Patients with nonfunctioning adrenal adenomas (NFA) and mild autonomous cortisol secretion (MACS) demonstrate an increased risk of chronic kidney disease (CKD), however factors associated with CKD are unknown. We aimed to identify the factors associated with CKD and assess the impact of adrenalectomy on kidney function in patients with NFA or MACS. DESIGN: Single-center cohort study of patients with NFA and MACS, 1999-2020. METHODS: MACS was diagnosed based on post-dexamethasone cortisol (DST) ≥ 1.8 mcg/dL. Age, sex, dysglycemia, hypertension, therapy with statin, angiotensin converting enzyme inhibitor, or angiotensin II receptor blocker were included in the multivariable analysis. Outcomes included estimated glomerular filtration rate (eGFR) at the time of diagnosis with MACS or NFA and post-adrenalectomy delta eGFR. RESULTS: Of 972 patients, 429 (44%) had MACS and 543 (56%) had NFA. At the time of diagnosis, patients with MACS had lower eGFR (median 79.6 vs 83.8 ml/min/1.73m2, p < 0.001) than patients with NFA. In a multivariable analysis, factors associated with lower eGFR were older age, hypertension, and higher DST. In 204 patients (MACS: 155, 76% and NFA: 49, 24%) treated with adrenalectomy, post adrenalectomy eGFR improved in both groups starting at 18 months up to 3.5 years of follow up. Factors associated with increased eGFR were younger age, lower pre-adrenalectomy eGFR and longer follow-up period. CONCLUSION: DST cortisol is an independent risk factor for lower eGFR in patients with adrenal adenomas. Both patients with MACS and NFA demonstrate an increase in eGFR post-adrenalectomy, especially younger patients with lower eGFR pre-adrenalectomy.

Extracellular Cysteine Proteases of Key Intestinal Protozoan Pathogens-Factors Linked to Virulence and Pathogenicity.

Intestinal diseases caused by protistan parasites of the genera Giardia (giardiasis), Entamoeba (amoebiasis), Cryptosporidium (cryptosporidiosis) and Blastocystis (blastocystosis) represent a major burden in human and animal populations worldwide due to the severity of diarrhea and/or inflammation in susceptible hosts. These pathogens interact with epithelial cells, promoting increased paracellular permeability and enterocyte cell death (mainly apoptosis), which precede physiological and immunological disorders. Some cell-surface-anchored and molecules secreted from these parasites function as virulence markers, of which peptide hydrolases, particularly cysteine proteases (CPs), are abundant and have versatile lytic activities. Upon secretion, CPs can affect host tissues and immune responses beyond the site of parasite colonization, thereby increasing the pathogens' virulence. The four intestinal protists considered here are known to secrete predominantly clan A (C1- and C2-type) CPs, some of which have been characterized. CPs of Giardia duodenalis (e.g., Giardipain-1) and Entamoeba histolytica (EhCPs 1-6 and EhCP112) degrade mucin and villin, cause damage to intercellular junction proteins, induce apoptosis in epithelial cells and degrade immunoglobulins, cytokines and defensins. In Cryptosporidium, five Cryptopains are encoded in its genome, but only Cryptopains 4 and 5 are likely secreted. In Blastocystis sp., a legumain-activated CP, called Blastopain-1, and legumain itself have been detected in the extracellular medium, and the former has similar adverse effects on epithelial integrity and enterocyte survival. Due to their different functions, these enzymes could represent novel drug targets. Indeed, some promising results with CP inhibitors, such as vinyl sulfones (K11777 and WRR605), the garlic derivative, allicin, and purified amoebic CPs have been obtained in experimental models, suggesting that these enzymes might be useful drug targets.

High prevalence of frailty in patients with adrenal adenomas and adrenocortical hormone excess: a cross-sectional multi-centre study with prospective enrolment.

OBJECTIVE: Frailty, characterized by multi-system decline, increases vulnerability to adverse health outcomes and can be measured using Frailty Index (FI). We aimed to assess the prevalence of frailty in patients with adrenal disorders (based on hormonal sub-type) and examine association between FI and performance-based measures of physical function. DESIGN: Multi-centre, cross-sectional study (March 2019-August 2022). METHODS: Adult patients with adrenal disorders (non-functioning adrenal adenomas [NFA], mild autonomous cortisol secretion [MACS], Cushing syndrome [CS], primary aldosteronism [PA]) and referent subjects without adrenal disorders completed a questionnaire encompassing 47 health variables (comorbidities, symptoms, daily living activities). FI was calculated as the average score of all variables and frailty defined as FI ≥ 0.25. Physical function was assessed with hand grip, timed up-and-go test, chair rising test, 6-minute walk test, and gait speed. RESULTS: Compared to referent subjects (n = 89), patients with adrenal disorders (n = 520) showed increased age, sex, and body mass index-adjusted prevalence of frailty (CS [odds ratio-OR 19.2, 95% confidence interval-CI 6.7-70], MACS [OR 12.5, 95% CI 4.8-42.9], PA [OR 8.4, 95% CI 2.9-30.4], NFA [OR 4.5, 95% CI 1.7-15.9]). Prevalence of frailty was similar to referent subjects when post-dexamethasone cortisol was <28 nmol/L and was higher when post-dexamethasone cortisol was 28-50 nmol/L (OR 4.6, 95% CI 1.7-16.5). FI correlated with all measures of physical function (P < .001). CONCLUSIONS: Whilst frailty prevalence was highest in patients with adrenocortical hormone excess, even patients with NFA demonstrated an increased prevalence compared to the referent population. Future longitudinal studies are needed to evaluate the impact of various management strategies on frailty.

Payment Methods and Demographics Influence Patterns of Dental Service Utilization.

OBJECTIVE: To describe the patterns of specific dental service utilization among the various sociodemographic groups in North Carolina served by the East Carolina University School of Dental Medicine (ECU SoDM). DESIGN: This was a descriptive study utilizing self-reported patients' sociodemographic information, payment method history, and CDT codes of procedures performed. Deidentified clinical data recorded for 26 710 patients and 534 983 procedures from 2011 to 2020 were extracted from a centralized axiUm database. Data were analyzed using IBM SPSS Statistics, version 25.0. Cross-tabulations between dental service utilizations, patients' demographics, and payment method were performed using chi-square analysis. SETTING: Nine dental clinic sites across the state of North Carolina. PARTICIPANTS: In total, 26 710 adults 23 years to older than 65 years were included in the sample for this study. MAIN OUTCOME MEASURES: In total, 534 983 procedure codes completed for the eligible patients were cross-tabulated with payment method. RESULTS: Payment method was significantly related to individual characteristics including location of service, age, race, ethnicity, and untreated decay ( P < .001). Payment method is associated with the dental service type utilized by an individual ( P < .001). Patients who received Medicaid benefits were more likely to receive restorative procedures, removable prosthetics, or oral surgery. Despite NC Medicaid covering preventive procedures, patients who received Medicaid benefits showed lower utilization of preventive procedures than expected. Privately insured or self-paying individuals demonstrated a greater variety of service option utilization, as well as more frequent usage of more specialized procedure options such as endodontics, periodontics, fixed prosthodontics, and implants. CONCLUSIONS: Payment method was found to be related to patients' demographics and type of dental service utilized. Adults older than 65 years demonstrated a higher proportion of self-payment for dental care, indicating a lack of payment options for this population. In the interest of providing care for underserved populations in North Carolina, policy makers should consider expanding dental coverage for adults older than 65 years.

Effect of being overweight and obese on periodontal treatment costs.

BACKGROUND: Obesity can increase a person's risk of developing periodontal disease, and patients with obesity have greater health care costs. However, the effect of obesity on periodontal treatment costs has not been examined. METHODS: This retrospective cohort study used data from the electronic dental records of adult patients examined from July 1, 2010, through July 31, 2019 at a US dental school. Primary exposure was body mass index, which was categorized as obese, overweight, or normal. Periodontal disease was categorized using clinical probing measures. Fee schedules and procedure codes were used to compute the primary outcome, which was total periodontal treatment costs. A generalized linear model with gamma distribution was used to examine the relationship between body mass index and periodontal costs after controlling for initial periodontal disease severity and other confounding variables. Parameter coefficients and mean ratios with 95% CIs were estimated. RESULTS: The study sample included 3,443 adults, of whom 39% were normal weight, 37% were overweight, and 24% were obese. Mean (SD) total periodontal treatment costs for patients who were obese were considerably higher ($420 [$719]) than those for patients who were overweight ($402 [$761]) and patients who were normal weight ($268 [$601]). After controlling for covariates and disease severity, patients who were obese had 27% higher periodontal treatment costs than patients who were normal weight. The additional periodontal treatment costs attributable to obesity were greater than those attributable to either diabetes or smoking. CONCLUSIONS: The study results suggest that among patients at a dental school, those who were obese incurred substantially higher periodontal treatment costs than patients who were normal weight, independent of initial periodontal disease severity. PRACTICAL IMPLICATIONS: The study findings have important implications for clinical guidelines and dental benefit design and coverage policies.

Bariatric Weight Loss Surgery Improves Systolic Function in Obese Patients With Heart Failure.

Obesity has become a worldwide public health issue. Many obese patients concomitantly suffer with heart failure with reduced ejection fraction. There have been reports of improvement in left ventricular systolic function following significant weight loss after bariatric surgery. We sought to investigate this phenomenon within our institution. This was a retrospective single-center analysis of patients conducted between 2010 and 2019. The study included patients with morbid obesity (body mass index >35 kg/m2 and an obesity-related comorbid condition, or a body mass index >40 kg/m2) and left ventricular systolic dysfunction. Analysis was performed based on systolic function recovery after bariatric surgery and advanced heart failure therapy. Of the 190 patients identified, 57 patients had a left ventricular ejection fraction of <40%. Twenty-two patients underwent bariatric surgery, of which at least 54.5% had systolic function recovery. Patients who had systolic function recovery after bariatric surgery were significantly older (51.58 years ± 10.48 vs 32.3 years ± 5.03, P = 0.001). Older age and female sex were predictors of systolic function recovery. In patients with obesity and heart failure with reduced ejection fraction, weight loss following bariatric surgery was shown to be correlated with significant improvement in left ventricular systolic function.

Dp71 Point Mutations Induce Protein Aggregation, Loss of Nuclear Lamina Integrity and Impaired Braf35 and Ibraf Function in Neuronal Cells.

Dystrophin Dp71 is the most abundant product of the Duchenne muscular dystrophy gene in the nervous system, and mutations impairing its function have been associated with the neurodevelopmental symptoms present in a third of DMD patients. Dp71 is required for the clustering of neurotransmitter receptors and the neuronal differentiation of cultured cells; nonetheless, its precise role in neuronal cells remains to be poorly understood. In this study, we analyzed the effect of two pathogenic DMD gene point mutations on the Dp71 function in neurons. We engineered C272Y and E299del mutations to express GFP-tagged Dp71 protein variants in N1E-115 and SH-SY5Y neuronal cells. Unexpectedly, the ectopic expression of Dp71 mutants resulted in protein aggregation, which may be mechanistically caused by the effect of the mutations on Dp71 structure, as predicted by protein modeling and molecular dynamics simulations. Interestingly, Dp71 mutant variants acquired a dominant negative function that, in turn, dramatically impaired the distribution of different Dp71 protein partners, including ß-dystroglycan, nuclear lamins A/C and B1, the high-mobility group (HMG)-containing protein (BRAF35) and the BRAF35-family-member inhibitor of BRAF35 (iBRAF). Further analysis of Dp71 mutants provided evidence showing a role for Dp71 in modulating both heterochromatin marker H3K9me2 organization and the neuronal genes' expression, via its interaction with iBRAF and BRAF5.

Arthroscopic Disc Repositioning Techniques of the Temporomandibular Joint Part 2: Resorbable Pins.

Arthroscopic rigid fixation (ARF) of the temporomandibular joint (TMJ) with resorbable pins and other advanced arthroscopic disc repositioning (ADR) techniques by sutures has provided a renewed interest in the role played by the disc in the treatment of the most severe cases of TMJ ID with anterior disc displacement with severe limitation of mouth opening. These techniques may be the last step prior to open TMJ surgery, if other less complex operative arthroscopic techniques (OAT) have previously failed, or for those cases in which no predictable results are expected with simpler OAT due to the presence of a severe displaced disc or closed lock. In this article, ARF with resorbable pins is being approached, with a special focus on describing the technique while reporting its advantages and disadvantages. Also, potential complications and postoperative management and recovery, together with some advice in terms of pearls and pitfalls will be exposed.

Giardia duodenalis enolase is secreted as monomer during trophozoite-epithelial cell interactions, activates plasminogen and induces necroptotic damage.

Enolase, a multifunctional protein expressed by multiple pathogens activates plasminogen to promote proteolysis on components of the extracellular matrix, an important event in early host-pathogen interactions. A secreted form of enolase that is released upon the interaction of trophozoites with epithelial cells has been detected in the secretome of G. duodenalis. However, the role of enolase in the host-pathogen interactions remains largely unknown. In this work, the effects of G. duodenalis enolase (Gd-eno) on the epithelial cell model (IEC-6) were analyzed. Firstly, the coding sequence of Giardia enolase was cloned and the recombinant protein used to raise antibodies that were then used to define the localization and role of enolase in epithelial cell-trophozoite interactions. Gd-eno was detected in small cytoplasmic vesicles as well as at the surface and is enriched in the region of the ventral disk of Giardia trophozoites. Moreover, the blocking of the soluble monomeric form of the enzyme, which is secreted upon interaction with IEC-6 cells by the anti-rGd-eno antibodies, significantly inhibited trophozoite attachment to intestinal IEC-6 cell monolayers. Further, rGd-eno was able to bind human plasminogen (HsPlg) and enhanced plasmin activity in vitro when the trophozoites were incubated with the intrinsic plasminogen activators of epithelial cells. In IEC-6 cells, rGd-eno treatment induced a profuse cell damage characterized by copious vacuolization, intercellular separation and detachment from the substrate; this effect was inhibited by either anti-Gd-eno Abs or the plasmin inhibitor ϵ- aminocaproic acid. Lastly, we established that in epithelial cells rGd-eno treatment induced a necroptotic-like process mediated by tumor necrosis factor α (TNF-α) and the apoptosis inducing factor (AIF), but independent of caspase-3. All together, these results suggest that Giardia enolase is a secreted moonlighting protein that stimulates a necroptotic-like process in IEC-6 epithelial cells via plasminogen activation along to TNFα and AIF activities and must be considered as a virulence factor.

Use of primary bariatric surgery among patients with obesity and diabetes. Insights from the Diabetes Collaborative Registry.

Despite its cardiometabolic benefits, bariatric surgery has historically been underused in patients with obesity and diabetes, but contemporary data are lacking. Among 1,520,182 patients evaluated from 2013 to 2019 within a multicenter, longitudinal, US registry of outpatients with diabetes, we found that 462,033 (30%) met eligibility for bariatric surgery. After a median follow-up of 854 days, 6310/384,859 patients (1.6%) underwent primary bariatric surgery, with a slight increase over time (0.38% per year [2013] to 0.68% per year [2018]). Patients who underwent bariatric surgery were more likely to be female (63% vs. 56%), white (87% vs. 82%), have higher body mass indices (42.1 ± 6.9 vs. 40.6 ± 5.9 kg/m2), and depression (23% vs. 14%; p < 0.001 for all). Over a median (IQR) follow-up after surgery of 722 days (364-993), patients who underwent bariatric surgery had lost an average of 11.8 ± 18.5 kg (23% of excess body weight), 10.2% were on fewer glucose-lowering medications, and 8.4% were on fewer antihypertensives. Despite bariatric surgery being safer and more accessible over the past two decades, less than one in fifty eligible patients with diabetes receive this therapy.