ABSTRACT
Pancreatic ß-cells are essential for survival, being the only cell type capable of insulin secretion. While they are believed to be vulnerable to damage by inflammatory cytokines such as interleukin-1 beta (IL-1ß) and interferon-gamma, we have recently identified physiological roles for cytokine signaling in rodent ß-cells that include the stimulation of antiviral and antimicrobial gene expression and the inhibition of viral replication. In this study, we examine cytokine-stimulated changes in gene expression in human islets using single-cell RNA sequencing. Surprisingly, the global responses of human islets to cytokine exposure were remarkably blunted compared to our previous observations in the mouse. The small population of human islet cells that were cytokine responsive exhibited increased expression of IL-1ß-stimulated antiviral guanylate-binding proteins, just like in the mouse. Most human islet cells were not responsive to cytokines, and this lack of responsiveness was associated with high expression of genes encoding ribosomal proteins. We further correlated the expression levels of RPL5 with stress response genes, and when expressed at high levels, RPL5 is predictive of failure to respond to cytokines in all endocrine cells. We postulate that donor causes of death and isolation methodologies may contribute to stress of the islet preparation. Our findings indicate that activation of stress responses in human islets limits cytokine-stimulated gene expression, and we urge caution in the evaluation of studies that have examined cytokine-stimulated gene expression in human islets without evaluation of stress-related gene expression.
Subject(s)
Cytokines , Islets of Langerhans , Single-Cell Analysis , Humans , Single-Cell Analysis/methods , Islets of Langerhans/metabolism , Islets of Langerhans/drug effects , Cytokines/metabolism , Cytokines/genetics , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/drug effects , Sequence Analysis, RNA , Stress, Physiological/drug effects , Interleukin-1beta/metabolism , Ribosomal Proteins/genetics , Ribosomal Proteins/metabolism , Male , Mice , Animals , RNA-Seq , Female , Middle Aged , Single-Cell Gene Expression AnalysisABSTRACT
BACKGROUND: Metabolic and Bariatric Surgery (MBS) is the most effective management for patients with obesity and weight-related medical conditions. Duodenal switch (DS) is a recent MBS procedure with increasing attention in recent years, however the risk of anastomotic or staple line leaks and the lack of efficient surgical expertise hinders the procedure from becoming fully adopted. OBJECTIVES: To determine the 30-day predictors of leaks following DS and explore their association with other 30-day postoperative complications. SETTING: Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database. METHODS: Patients who underwent a primary biliopancreatic diversion with DS or single-anastomosis duodenoileostomy with sleeve procedure, categorized as DS, were assessed for 30-day leaks. A multivariable logistic regression was constructed to identify the predictors of leaks. The assessment of postoperative complications arising from leaks was also performed. RESULTS: A total of 21,839 DS patients were included, of which 177 (.8%) experienced leaks within 30 postoperative days. The most significant predictor of leaks was steroid immunosuppressive use (adjusted odds ratio [aOR] = 3.01, 95% confidence interval [CI] [1.56-5.13], P < .001) and age, with each decade of life associated with a 26% increase in risk (aOR = 1.26, 95% CI [1.09-1.45], P = .001). Operative length was also associated with leaks, with every additional 30 minutes increasing the odds of a leak by 23% (aOR = 1.23, 95% CI [1.18-1.29], P < .001). The occurrence of leaks was correlated with postoperative septic shock (Crude Odds Ratio [COR] = 280.99 [152.60-517.39]) and unplanned intensive care unit (ICU) admissions (COR = 79.04 [56.99-109.59]). Additionally, mortality rates increased 17-fold with the incidence of leaks (COR = 17.64 [7.41-41.99]). CONCLUSIONS: Leaks following DS are a serious postoperative complication with significant risk factors of steroid use, prolonged operative time and advanced age. Leaks are also associated with other severe complications, highlighting the need for early diagnosis and intervention along with additional studies to further validate our results.
ABSTRACT
Recent advances in machine learning (ML) have led to newer model architectures including transformers (large language models, LLMs) showing state of the art results in text generation and image analysis as well as few-shot learning (FSLC) models which offer predictive power with extremely small datasets. These new architectures may offer promise, yet the 'no-free lunch' theorem suggests that no single model algorithm can outperform at all possible tasks. Here, we explore the capabilities of classical (SVR), FSLC, and transformer models (MolBART) over a range of dataset tasks and show a 'goldilocks zone' for each model type, in which dataset size and feature distribution (i.e. dataset "diversity") determines the optimal algorithm strategy. When datasets are small ( < 50 molecules), FSLC tend to outperform both classical ML and transformers. When datasets are small-to-medium sized (50-240 molecules) and diverse, transformers outperform both classical models and few-shot learning. Finally, when datasets are of larger and of sufficient size, classical models then perform the best, suggesting that the optimal model to choose likely depends on the dataset available, its size and diversity. These findings may help to answer the perennial question of which ML algorithm is to be used when faced with a new dataset.
ABSTRACT
The role of the social, physical, and organisational environments in shaping how patients and their caregivers perform work remains largely unexplored in human factors/ergonomics literature. This study recruited 19 dyads consisting of a parent and their child with type 1 diabetes to be interviewed individually and analysed using a macroergonomic framework. Our findings aligned with the macroergonomic factors as presented in previous models, while highlighting the need to expand upon certain components to gain a more comprehensive representation of the patient work system as relevant to dyadic management. Examples of design efforts that should follow from these findings include expanding existing data sharing options to include information from the external environment and capitalising on the capabilities of artificial intelligence as a decision support system. Future research should focus on longitudinally assessing patient work systems throughout transition periods in addition to more explicitly exploring the roles of social network members.
Work performed by patients and their caregivers is shaped by the social, physical, and organisational contexts they are embedded within. This paper explored how adolescents with type 1 diabetes managed their health alongside their parents in the context of these macroergonomic factors. These findings have implications for research and design.
ABSTRACT
Inhibition of the bromodomain and extraterminal domain (BET) protein family is a potential strategy to prevent and treat diabetes; however, the clinical use of BET bromodomain inhibitors (BETis) is associated with adverse effects. Here, we explore a strategy for targeting BETis to ß cells by exploiting the high-zinc (Zn2+) concentration in ß cells relative to other cell types. We report the synthesis of a novel, Zn2+-chelating derivative of the pan-BETi (+)-JQ1, (+)-JQ1-DPA, in which (+)-JQ1 was conjugated to dipicolyl amine (DPA). As controls, we synthesized (+)-JQ1-DBA, a non-Zn2+-chelating derivative, and (-)-JQ1-DPA, an inactive enantiomer that chelates Zn2+. Molecular modeling and biophysical assays showed that (+)-JQ1-DPA and (+)-JQ1-DBA retain potent binding to BET bromodomains in vitro. Cellular assays demonstrated (+)-JQ1-DPA attenuated NF-ĸB target gene expression in ß cells stimulated with the proinflammatory cytokine interleukin 1ß. To assess ß-cell selectivity, we isolated islets from a mouse model that expresses green fluorescent protein in insulin-positive ß cells and mTomato in insulin-negative cells (non-ß cells). Surprisingly, Zn2+ chelation did not confer ß-cell selectivity as (+)-JQ1-DPA was equally effective in both ß and α cells; however, (+)-JQ1-DPA was less effective in macrophages, a nonendocrine islet cell type. Intriguingly, the non-Zn2+-chelating derivative (+)-JQ1-DBA displayed the opposite selectivity, with greater effect in macrophages compared with (+)-JQ1-DPA, suggesting potential as a macrophage-targeting molecule. These findings suggest that Zn2+-chelating small molecules confer endocrine cell selectivity rather than ß-cell selectivity in pancreatic islets and provide valuable insights and techniques to assess Zn2+ chelation as an approach to selectively target small molecules to pancreatic ß cells.NEW & NOTEWORTHY Inhibition of BET bromodomains is a novel potential strategy to prevent and treat diabetes mellitus. However, BET inhibitors have negative side effects. We synthesized a BET inhibitor expected to exploit the high zinc concentration in ß cells to accumulate in ß cells. We show our inhibitor targeted pancreatic endocrine cells; however, it was less effective in immune cells. A control inhibitor showed the opposite effect. These findings help us understand how to target specific cells in diabetes treatment.
Subject(s)
Chelating Agents , Insulin-Secreting Cells , Zinc , Animals , Zinc/chemistry , Zinc/pharmacology , Zinc/metabolism , Chelating Agents/pharmacology , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Mice , Transcription Factors/metabolism , Transcription Factors/antagonists & inhibitors , Triazoles/pharmacology , Triazoles/chemistry , Humans , Male , Azepines/pharmacology , Azepines/chemistry , Glucagon-Secreting Cells/drug effects , Glucagon-Secreting Cells/metabolism , Mice, Inbred C57BL , Bromodomain Containing Proteins , Nuclear ProteinsABSTRACT
Nitric oxide is produced at low micromolar levels following the induction of inducible nitric oxide synthase (iNOS) and is responsible for mediating the inhibitory actions of cytokines on glucose-stimulated insulin secretion by islets of Langerhans. It is through the inhibition of mitochondrial oxidative metabolism, specifically aconitase and complex 4 of the electron transport chain, that nitric oxide inhibits insulin secretion. Nitric oxide also attenuates protein synthesis, induces DNA damage, activates DNA repair pathways, and stimulates stress responses (unfolded protein and heat shock) in ß-cells. In this report, the time- and concentration-dependent effects of nitric oxide on the expression of six genes known to participate in the response of ß-cells to this free radical were examined. The genes included Gadd45α (DNA repair), Puma (apoptosis), Hmox1 (antioxidant defense), Hsp70 (heat shock), Chop (UPR), and Ppargc1α (mitochondrial biogenesis). We show that nitric oxide stimulates ß-cell gene expression in a narrow concentration range of â¼0.5-1 µM or levels corresponding to iNOS-derived nitric oxide. At concentrations greater than 1 µM, nitric oxide fails to stimulate gene expression in ß-cells, and this is associated with the inhibition of mitochondrial oxidative metabolism. This narrow concentration range of responses is ß-cell selective, as the actions of nitric oxide in non-ß-cells (α-cells, mouse embryonic fibroblasts, and macrophages) are concentration dependent. Our findings suggest that ß-cells respond to a narrow concentration range of nitric oxide that is consistent with the levels produced following iNOS induction, and that these concentration-dependent actions are selective for insulin-containing cells.
Subject(s)
Apoptosis Regulatory Proteins , Gene Expression Regulation , Insulin-Secreting Cells , Nitric Oxide Synthase Type II , Nitric Oxide , Animals , Nitric Oxide/metabolism , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/drug effects , Mice , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/genetics , Gene Expression Regulation/drug effects , Apoptosis Regulatory Proteins/metabolism , Apoptosis Regulatory Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Transcription Factor CHOP/metabolism , Transcription Factor CHOP/genetics , HSP70 Heat-Shock Proteins/metabolism , HSP70 Heat-Shock Proteins/genetics , Heme Oxygenase (Decyclizing)/metabolism , Heme Oxygenase (Decyclizing)/genetics , Cell Cycle Proteins/metabolism , Cell Cycle Proteins/genetics , Insulin/metabolism , Proto-Oncogene Proteins/metabolism , Proto-Oncogene Proteins/genetics , Rats , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Membrane Proteins , Heme Oxygenase-1ABSTRACT
BACKGROUND: Metabolic and bariatric surgery (MBS), despite being the most effective durable treatment for obesity, remains underused as approximately 1% of all qualified patients undergo surgery. The American Society for Metabolic and Bariatric Surgery established a Numbers Taskforce to specify the annual rate of obesity treatment interventions utilization and to determine if patients in need are receiving appropriate treatment. OBJECTIVE: To provide the best estimated number of metabolic and bariatric procedures being performed in the United States in 2022. SETTING: United States. METHODS: We reviewed data from the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program and National Surgical Quality Improvement Program. In addition, data from industry and state databases were used to estimate activity at non-accredited centers. Data from 2022 were compared mainly with data from the previous 2 years. RESULTS: Compared with 2021, the total number of MBS performed in 2022 increased from approximately 262,893 to 280,000. The sleeve gastrectomy (SG) continues to be the most commonly performed procedure. The gastric bypass procedure trend remained relatively stable. The percentage of revision procedures and biliopancreatic diversion with duodenal switch procedures increased slightly. Intragastric balloon placement increased from the previous year. Endoscopic sleeve gastroplasty increased in numbers. CONCLUSIONS: There was a 6.5% increase in MBS volume from 2021 to 2022 and a 41% increase from 2020, which demonstrates a recovery from the COVID-19 pandemic. SG continues to be the most dominant MBS procedure.
Subject(s)
Bariatric Surgery , Humans , Bariatric Surgery/statistics & numerical data , Bariatric Surgery/methods , United States , Societies, Medical , Obesity, Morbid/surgery , Obesity/surgery , Obesity/epidemiologyABSTRACT
IMPORTANCE: No single cognitive screen adequately captures all cognitive domains that are important for inpatient occupational therapy treatment planning. OBJECTIVE: To quantify the content validity of a novel 22-item cognitive screen, the Gaylord Occupational Therapy Cognitive (GOT-Cog) screen, developed to better inform inpatient occupational therapy treatment planning. DESIGN: Delphi-style expert panel review. SETTING: Long-term acute care hospital. PARTICIPANTS: The first panel was attended by four occupational therapists, two speech-language pathologists, one physician assistant, and two neuropsychologists; the second, by four occupational therapists, one speech-language pathologist, and one physician assistant. INTERVENTION: Each Delphi panel discussed the relevance, essentiality, and clarity of each item. After each discussion, panelists completed a content validity survey to summarize their evaluation of each item. OUTCOMES AND MEASURES: On the basis of panelists' survey responses, item- and scale-level relevance, essentiality, and clarity were quantified by calculating the respective content validity index (CVI), content validity ratio (CVR), and content clarity index (CCI). Universal agreement (UA) and κ statistics were also calculated, as appropriate. RESULTS: Upon presenting the initial 23-item instrument covering 10 cognitive domains to the first Delphi panel, several questions were added, removed, or rewritten, resulting in a 22-item instrument representing nine domains. After the second panel, several questions were again rewritten, and the domains reorganized. All scale-level metrics improved, including CVI (from 0.87 to 1.0), UA (0.52 to 1.0), CVR (0.43 to 0.94), and CCI (2.26 to 2.92). CONCLUSIONS AND RELEVANCE: GOT-Cog displays overall excellent content validity and can proceed to construct validity testing. Plain-Language Summary: By reporting on the content validity of the Gaylord Occupational Therapy Cognitive screen, this brief report begins the necessary process of evaluating the measure's overall validity and reliability.
Subject(s)
Occupational Therapy , Humans , Inpatients , Reproducibility of Results , Occupational Therapists , CognitionABSTRACT
BACKGROUND: The use of tourniquets and their role in extremity-based microsurgery has not been thoroughly investigated. The purpose of this study was to investigate tourniquet use and its associated outcomes and complications. The authors hypothesize that tourniquets enhance visualization, bloodless approaches to vessel harvest, flap elevation, and anastomosis without added complications. METHODS: A retrospective chart review was completed for patients who had undergone extremity-based microsurgery with the use of a tourniquet between January 2018 and February 2022 at two large academic institutions. Demographic characteristics, initial reasons for surgery, complications, and outcomes were recorded. Patients were separated into groups based on tourniquet use during three operative segments: (1) flap elevation, (2) vessel harvest, and (3) microvascular anastomosis. An internal comparison of complication rate was performed between cases for which a tourniquet was used for one operative segment to all cases in which it was not used for the same operative segment. Univariate and multivariate statistical analyses were performed to identify statistically significant results. RESULTS: A total of 99 patients (106 surgeries) were included in this study across sites. The mean age was 41.2 years and 67.7% of the patients were male. The most common reason for microsurgical reconstruction was trauma (50.5%). The need for an additional unplanned surgery was the most common surgical complication (16%). A total of 70, 61, and 32% of procedures used a tourniquet for flap elevation, vessel harvest, and for anastomosis, respectively. Statistical analyses identified no difference in complication rates for procedures for which a tourniquet was or was not used for interventions. CONCLUSION: Based on these results, the authors state that tourniquets can be utilized for extremity-based microsurgery to enable bloodless dissection without the concern of increased complication rates.
Subject(s)
Microsurgery , Tourniquets , Humans , Male , Adult , Female , Retrospective Studies , Tourniquets/adverse effects , Extremities/blood supply , Surgical FlapsABSTRACT
BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database collects data from all accredited centers in the US. A prior study showed data quality issues limiting use of up to 20% of the 2015 database. OBJECTIVES: To evaluate the completeness and data quality (internal validity, accuracy, and consistency) of the MBSAQIP database between 2015 and 2019. SETTING: United States. METHODS: All subsets of data from the MBSAQIP Participant User Data File (PUDF) were compiled into one main file. Completeness, internal validity, accuracy, and consistency were evaluated. Completeness was determined via missing values. Internal validity was assessed using the percentage of patients with a body mass index (BMI) < 30 kg/m2 who underwent primary bariatric surgery. Accuracy was evaluated using reported versus calculated BMI. Consistency was assessed using the percentage of patients with a gain of >5 or a loss of >20 units of BMI change in 30 days. Effects across years were assessed using a chi-squared test. RESULTS: Missing data for age, BMI, and ASA was consistently low (<2.5%) with no significant difference across years. Only .02% of patients who underwent a primary bariatric procedure had a reported BMI <30 kg/m2. The mean difference between reported versus calculated BMI was -.02 units. A maximum of .33% of patients gained >5 units of BMI, and a maximum of .85% of patients lost > 20 units of BMI in early follow-up. CONCLUSIONS: While the MBSAQIP is a database with acceptable data quality and minimal changes from 2015-2019, ongoing efforts are needed to improve data.
Subject(s)
Bariatric Surgery , Gastric Bypass , Obesity, Morbid , Humans , United States/epidemiology , Child, Preschool , Obesity, Morbid/surgery , Quality Improvement , Treatment Outcome , Bariatric Surgery/methods , Accreditation , Retrospective Studies , Gastrectomy/methodsABSTRACT
BACKGROUND: Adjustable gastric bands (AGB) are frequently converted to sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) due to weight recurrence or band complications. Such conversions carry a higher-risk than primary procedures. Some patients undergo two conversions-from AGB to SG, and subsequently from SG to RYGB. This presents a unique situation with limited literature on indications and complication rates associated with these double conversions. METHODS: We examined the 2020-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Participant Use File to evaluate conversions from AGB to SG and then to RYGB. Patient and operative characteristics, along with outcomes, were evaluated. Descriptive statistics were applied. RESULTS: We identified 276 patients who underwent a conversion from AGB to SG and then to RYGB. The primary reason for the second conversion (SG to RYGB) was gastroesophageal reflux disease (GERD) at 55.1%, followed by inadequate weight loss or weight regain (IWL/WR) at 36.9%. The remaining reasons included dysphagia, nausea, vomiting, or others. Patients converted for IWL/WR demonstrated a higher baseline body mass index and prevalence of sleep apnea compared to other cohorts (both p < 0.001). Meanwhile, patients in the "other reasons" group had the highest rate of open surgical approaches (9.1%) and concurrent lysis of adhesions (p = 0.001 and p = 0.022), with correspondingly higher rates of anastomotic leak, reoperations, serious complications, and mortality. CONCLUSIONS: Patients undergoing double conversions (AGB to SG to RYGB) do so primarily for GERD or IWL/WR. Further research is required to better define the optimal primary operation for each patient, aiming to reduce the necessity for multiple conversions.
Subject(s)
Gastric Bypass , Gastroesophageal Reflux , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Obesity, Morbid/complications , Retrospective Studies , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Gastric Bypass/adverse effects , Gastric Bypass/methods , Gastroesophageal Reflux/etiology , Gastroesophageal Reflux/surgery , Gastrectomy/methods , Weight Loss , Treatment OutcomeABSTRACT
BACKGROUND: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program evaluates 30-day outcomes of bariatric cases performed in the United States. The Participant Use File in 2020 introduced bowel obstruction (BO). We compared the rates of BO, risk factors, and postoperative outcomes after laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), and duodenal switch (DS). METHODS: Retrospective analysis of patients who underwent laparoscopic RYGB, SG, or DS obtained from the 2020-2021 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program. Patients who underwent either as a primary procedure with a body mass index >35 kg/m 2 were selected. Baseline characteristics, operative details, and postoperative complications were collected. The outcome of interest was BO occurring within 30 days. RESULTS: A total of 205,533 cases of which 148,944 were SG (72.4%), 54,606 were RYGB (26.5%), and 1983 were DS (1%). BO occurred in 0.74%, 0.4%, and 0.03% of patients who underwent an RYGB, DS, or SG, respectively. Patients with a BO in the RYGB group were more likely to be on immunosuppressive therapy (5.4% vs. 1.9%, P <0.001) with longer operative time (136.2 min±58.0 min vs. 117.4 min±53.6 min, P <0.001). SG patients with a BO were older (47.5±13.6 vs. 41.9±11.6, P =0.011) with longer operating times (98.6±63.8 vs. 68.9±33.4, P =0.002). Patients in the RYGB group with a BO had the highest rates of readmissions (71.9%) and reoperations (58.4%). CONCLUSIONS: Early bowel obstruction is rare after bariatric surgery. It is more common after RYGB and least common after SG. Readmission and reoperation rates were highest in patients with BO in the RYGB group.
Subject(s)
Bariatric Surgery , Gastric Bypass , Intestinal Obstruction , Obesity, Morbid , Humans , United States , Obesity, Morbid/surgery , Retrospective Studies , Treatment Outcome , Gastric Bypass/adverse effects , Gastric Bypass/methods , Bariatric Surgery/adverse effects , Bariatric Surgery/methods , Gastrectomy/adverse effects , Gastrectomy/methods , Intestinal Obstruction/epidemiology , Intestinal Obstruction/etiology , Intestinal Obstruction/surgeryABSTRACT
OBJECTIVE: Nutrition therapy for gestational diabetes mellitus (GDM) has conventionally focused on carbohydrate restriction. In a randomized controlled trial (RCT), we tested the hypothesis that a diet (all meals provided) with liberalized complex carbohydrate (60%) and lower fat (25%) (CHOICE diet) could improve maternal insulin resistance and 24-h glycemia, resulting in reduced newborn adiposity (NB%fat; powered outcome) versus a conventional lower-carbohydrate (40%) and higher-fat (45%) (LC/CONV) diet. RESEARCH DESIGN AND METHODS: After diagnosis (at â¼28-30 weeks' gestation), 59 women with diet-controlled GDM (mean ± SEM; BMI 32 ± 1 kg/m2) were randomized to a provided LC/CONV or CHOICE diet (BMI-matched calories) through delivery. At 30-31 and 36-37 weeks of gestation, a 2-h, 75-g oral glucose tolerance test (OGTT) was performed and a continuous glucose monitor (CGM) was worn for 72 h. Cord blood samples were collected at delivery. NB%fat was measured by air displacement plethysmography (13.4 ± 0.4 days). RESULTS: There were 23 women per group (LC/CONV [214 g/day carbohydrate] and CHOICE [316 g/day carbohydrate]). For LC/CONV and CHOICE, respectively (mean ± SEM), NB%fat (10.1 ± 1 vs. 10.5 ± 1), birth weight (3,303 ± 98 vs. 3,293 ± 81 g), and cord C-peptide levels were not different. Weight gain, physical activity, and gestational age at delivery were similar. At 36-37 weeks of gestation, CGM fasting (86 ± 3 vs. 90 ± 3 mg/dL), 1-h postprandial (119 ± 3 vs. 117 ± 3 mg/dL), 2-h postprandial (106 ± 3 vs. 108 ± 3 mg/dL), percent time in range (%TIR; 92 ± 1 vs. 91 ± 1), and 24-h glucose area under the curve values were similar between diets. The %time >120 mg/dL was statistically higher (8%) in CHOICE, as was the nocturnal glucose AUC; however, nocturnal %TIR (63-100 mg/dL) was not different. There were no between-group differences in OGTT glucose and insulin levels at 36-37 weeks of gestation. CONCLUSIONS: A â¼100 g/day difference in carbohydrate intake did not result in between-group differences in NB%fat, cord C-peptide level, maternal 24-h glycemia, %TIR, or insulin resistance indices in diet-controlled GDM.
Subject(s)
Diabetes, Gestational , Insulin Resistance , Pregnancy , Female , Infant, Newborn , Humans , Adiposity , C-Peptide , Random Allocation , Blood Glucose , Obesity , Glucose , Diet, Fat-RestrictedABSTRACT
BACKGROUND: Leak is a feared complication of bariatric surgeries. Time to presentation is important in their management. We used the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) to evaluate the rate and timing of leaks. OBJECTIVES: To determine when leaks present after bariatric surgery. SETTING: MBSAQIP database. METHODS: The MBSAQIP Participant Use Files (PUF) for the years 2015-2020 were evaluated. Outcomes of interest were "organ space infection" and "leak." We evaluated the time to presentation for these variables as well as patient characteristics, operative time, complication rates and 30-day outcomes. RESULTS: There were 370,369 sleeve gastrectomies (SG) and 159,280 Roux-en-Y gastric bypasses (RYGB). We identified 598 (.16%) SG leaks with an average time to presentation of 13.2 ± 7.8 days. For RYGB, there were 520 leaks (.32%) with an average time to presentation of 9.5 ± 7.4 days. Both procedures had longer operative times for the patients with leak; RYGB was 115 minutes versus 131 minutes and SG was 67 minutes versus 77 minutes (both P < .01). SG and RYGB patients with a leak had a higher relative risk (RR) of grade 4 and 5 Clavien-Dindo complication rates. RR of mortality rates in SG patients with leak was 35.2 (confidence interval (CI): 20-61) and in RYGB with leak was 31.4 (CI: 19-50). CONCLUSIONS: The length of time for SG leak presentation was more delayed than RYGB leak presentation. Surgeons should be vigilant for leaks for at least 3 weeks after surgery. Leaks increase the mortality rate and overall serious complications.
Subject(s)
Bariatric Surgery , Gastric Bypass , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Quality Improvement , Treatment Outcome , Retrospective Studies , Gastrectomy , AccreditationABSTRACT
INTRODUCTION: Because adolescence is a time of difficult management of Type 1 diabetes (T1D) in part from adolescent-parent shared responsibility of T1D management, our objective was to assess the effects of a decision support system (DSS) CloudConnect on T1D-related communication between adolescents and their parents and on glycemic management. METHODS: We followed 86 participants including 43 adolescents with T1D (not on automated insulin delivery systems, AID) and their parents/care-giver for a 12-week intervention of UsualCare + CGM or CloudConnect, which included a Weekly Report of automated T1D advice, including insulin dose adjustments, based on data from continuous glucose monitors (CGM), Fitbit and insulin use. Primary outcome was T1D-specific communication and secondary outcomes were hemoglobin A1c, time-in-target range (TIR) 70-180 mg/dl, and additional psychosocial scales. RESULTS: Adolescents and parents reported a similar amount of T1D-related communication in both the UsualCare + CGM or CloudConnect groups and had similar levels of final HbA1c. Overall blood glucose time in range 70-180 mg/dl and time below 70 mg/dl were not different between groups. Parents but not children in the CloudConnect group reported less T1D-related conflict; however, compared to the UsualCare + CGM group, adolescents and parents in the CloudConnect reported a more negative tone of T1D-related communication. Adolescent-parent pairs in the CloudConnect group reported more frequent changes in insulin dose. There were no differences in T1D quality of life between groups. CONCLUSIONS: While feasible, the CloudConnect DSS system did not increase T1D communication or provide improvements in glycemic management. Further efforts are needed to improve T1D management in adolescents with T1D not on AID systems.
ABSTRACT
This feasibility study aimed to trial a Free Water Protocol (FWP) for patients with thin liquid dysphagia in the Long-Term Acute Care Hospital (LTACH) setting. Patients with dysphagia are often prescribed thickened liquids to avoid or mitigate aspiration. While this clinical intervention can minimize the risk of aspiration pneumonia (PNA), it is generally not well received by patients. As such, the goal of this study was to determine if patients who knowingly aspirate thin liquids can safely tolerate thin liquid water, and if so, to what degree of benefit. The study assessed for adverse events, fluid intake, hydration status, quality of life, and overall swallow function outcomes. These measurements were taken over a 7 day trial period using inventories, lab work, clinical judgment, and observation. Ten participants were enrolled in this study with 9 having sufficient data for analysis (n = 9). No adverse events related to the FWP were observed, and patients saw improved total fluid intake (P = 0.0074), swallow-related quality of life (P = 0.0273), and overall swallow function (P = 0.0002). The results in this feasibility study allowed for the hospital wide implementation of the FWP and laid out the groundwork for future studies looking at longitudinal effects of a FWP.
Subject(s)
Deglutition Disorders , Pneumonia, Aspiration , Humans , Deglutition Disorders/therapy , Hospitals , Quality of Life , Water , Feasibility StudiesABSTRACT
Nitric oxide (NO) plays a dual role in regulating DNA damage response (DDR) signaling in pancreatic ß-cells. As a genotoxic agent, NO activates two types of DDR signaling; however, when produced at micromolar levels by the inducible isoform of NO synthase, NO inhibits DDR signaling and DDR-induced apoptosis in a ß-cell-selective manner. DDR signaling inhibition by NO correlates with mitochondrial oxidative metabolism inhibition and decreases in ATP and NAD+. Unlike most cell types, ß-cells do not compensate for impaired mitochondrial oxidation by increasing glycolytic flux, and this metabolic inflexibility leads to a decrease in ATP and NAD+. Here, we used multiple analytical approaches to determine changes in intermediary metabolites in ß-cells and non-ß-cells treated with NO or complex I inhibitor rotenone. In addition to ATP and NAD+, glycolytic and tricarboxylic acid cycle intermediates as well as NADPH are significantly decreased in ß-cells treated with NO or rotenone. Consistent with glucose-6-phosphate residing at the metabolic branchpoint for glycolysis and the pentose phosphate pathway (NADPH), we show that mitochondrial oxidation inhibitors limit glucose uptake in a ß-cell-selective manner. Our findings indicate that the ß-cell-selective inhibition of DDR signaling by NO is associated with a decrease in ATP to levels that fall significantly below the KM for ATP of glucokinase (glucose uptake) and suggest that this action places the ß-cell in a state of suspended animation where it is metabolically inert until NO is removed, and metabolic function can be restored.
Subject(s)
NAD , Nitric Oxide , Nitric Oxide/metabolism , NADP/metabolism , NAD/metabolism , Rotenone/pharmacology , DNA Damage , Adenosine Triphosphate/metabolism , Glucose/metabolismABSTRACT
BACKGROUND: The implications of operative time (OT) have been studied in different surgical specialties, showing a correlation with higher incidence rates of postoperative complications. However, the impact of OT on bariatric surgery complications is not well elucidated. METHODS: A retrospective review of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program database between 2015 and 2019 was performed. A total of 358,382 SG patients and 123,357 RYGB patients were included. The median OT was 68 min (10-720) and 113 min (10-640) for the sleeve gastrectomy (SG) group and the Roux-en-Y gastric bypass group, respectively. The groups were subdivided into two subgroups based on OT in comparison to the median time of each group. The subgroups were compared for surgical complications and outcomes. To reduce selection bias and risk of confounders, we performed a propensity score matching (PSM) for 22 variables. RESULTS: In the PSM-matched cohort, 18,915 SG and 6,495 RYGB patients were included in each subgroup. The SG cohort showed higher rates of Clavien-Dindo Class 1, 2, 3a, 4, and 5 complications as well as higher rates of readmission, reoperation, and reintervention in the longer OT group before matching. After PSM, the subgroup with longer times continued to have higher rates of Clavien-Dindo Class 2 complications and higher rates of readmission and reoperation. Similarly, there were higher rates of all Clavien-Dindo class complications as well as readmission, reoperation, and reintervention in the RYGB group with higher OT. After PSM, there were still higher rates of Clavien-Dindo Class 3a complications as well as readmission and reintervention in the RYGB subgroup with prolonged OT. CONCLUSION: In both SG and RYGB, longer OT was associated with increased rates of complications as well as readmission, reoperation, and reintervention. Surgeons should be cognizant of the increased rates of complications when operative times are longer.
Subject(s)
Bariatric Surgery , Gastric Bypass , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Obesity, Morbid/complications , Operative Time , Bariatric Surgery/adverse effects , Gastric Bypass/adverse effects , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/surgery , Gastrectomy/adverse effects , Retrospective Studies , Treatment OutcomeABSTRACT
INTRODUCTION/PURPOSE: One anastomosis gastric bypass (OAGB) and single anastomosis duodenoileostomy with sleeve (SADI-S) are two highly effective bariatric procedures that have been recently endorsed by the American Society of Metabolic and Bariatric Surgery (ASMBS). We compared the outcomes and safety profiles of SADI-S and OAGB using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database. MATERIALS AND METHODS: Retrospective analysis on patients who underwent SADI-S or OAGB obtained from the MBSAQIP database 2020-2021. Patients who underwent concurrent procedures (besides EGD) or had missing data were removed. Variables included age, sex, body mass index, American Society of Anesthesiologists (ASA) class, and pertinent medical comorbidities. Data were analyzed for 30-day postoperative morbidity, mortality, reoperation, reintervention, and readmissions. p values were calculated using Student's t-test or Fisher analysis. RESULTS: A total of 694 and 1068 patients respectively underwent SADI-S or OAGB. Statistically significant comorbidities included age (42.2 ± 10.8 vs. 43.7 ± 12.2), BMI (50.6 ± 9.1 vs. 45.3 ± 7.1), ASA 2 (66 (9.5%) vs. 165 (15.4%)), ASA 4 [69 (9.9%) vs. 20 (1.9%)], and immunosuppressive therapy [24 (3.5%) vs. 17 (1.6%)]. Clavien-Dindo-based analysis highlighted that SADI-S had higher grade 2 (p = 0.005) and grade 4b (p = 0.001) complications. Patients who underwent SADI-S were twice as likely to be readmitted within 30 days (3.7% vs. 1.9%; p = 0.021). CONCLUSION: SADI-S had higher readmission rates and higher Clavien-Dindo grade 2 and 4b complications. To note, SADI-S patients had higher BMIs. Further studies are needed to determine the long-term complications and efficacy of both operations.
Subject(s)
Bariatric Surgery , Gastric Bypass , Obesity, Morbid , Humans , Gastric Bypass/adverse effects , Gastric Bypass/methods , Obesity, Morbid/surgery , Retrospective Studies , Quality Improvement , Gastrectomy/methods , Bariatric Surgery/methods , AccreditationABSTRACT
Reactive oxygen species (ROS), such as hydrogen peroxide, are formed when molecular oxygen obtains additional electrons, increasing its reactivity. While low concentrations of hydrogen peroxide are necessary for regulation of normal cellular signaling events, high concentrations can be toxic. To maintain this balance between beneficial and deleterious concentrations of hydrogen peroxide, cells utilize antioxidants. Our recent work supports a primary role for peroxiredoxin, thioredoxin, and thioredoxin reductase as the oxidant defense pathway used by insulin-producing pancreatic ß-cells. These three players work in an antioxidant cycle based on disulfide exchange, with oxidized targets ultimately being reduced using electrons provided by NADPH. Peroxiredoxins also participate in hydrogen peroxide-based signaling through disulfide exchange with redox-regulated target proteins. This chapter will describe the catalytic mechanisms of thioredoxin, thioredoxin reductase, and peroxiredoxin and provide an in-depth look at the roles these enzymes play in antioxidant defense pathways of insulin-secreting ß-cells. Finally, we will evaluate the physiological relevance of peroxiredoxin-mediated hydrogen peroxide signaling as a regulator of ß-cell function.