Obesity Comorbidities Research Articles

Investigating the risk factors for isthmocele development after cesarean delivery

ObjectiveCesarean section (CS) rates are increasing globally, raising concerns about associated complications like isthmocele. Isthmoceles are pouch-like defects in the anterior uterine wall at the site of a prior CS scar. This study aimed to determine isthmocele prevalence, associated symptoms, and risk factors among women with a CS history. MethodsThis cross-sectional study evaluated 297 women with prior CS using transvaginal ultrasound to screen for isthmocele. Data on demographics, pregnancy details, comorbidities, and indications for CS were collected. Isthmocele was defined sonographically as any niche or defect at the hysterotomy site. Descriptive and comparative analyses identified factors associated with isthmocele. ResultsIsthmocele prevalence was 65.3% (n=194). Abnormal vaginal bleeding was reported by 21.1%, pelvic pain by 4.1%, and both by 4.1%. Compared to women without isthmocele, those with isthmocele were older (35.9 vs. 31.6 years), had higher BMI (26.8 vs. 25.5 kg/m2), gravidity (1.8 vs. 1.3), and parity (1.7 vs. 1.2). Repeat CS was more common (30.4% vs. 12.6%) and elective CS less common (33.5% vs. 67.9%) among those with isthmocele. ConclusionOver half of the women with CS history had an isthmocele. Abnormal bleeding was common. Advanced maternal age, obesity, repeat procedures, and certain comorbidities appear to increase risk. Further research on prevention and treatment is warranted given the high prevalence.

Hypertension and hyperglycaemia are positively correlated with local invasion of early cervical cancer.

Metabolic disorders are involved in the development of numerous cancers, but their association with the progression of cervical cancer is unclear. This study aims to investigate the association between metabolic disorders and the pathological risk factors and survival in patients with early cervical cancer. Patients with FIGO IB1 (2009) primary cervical cancer who underwent radical hysterectomy and systematic pelvic lymph node dissection at our institution from October 2014 to December 2017 were included retrospectively. Clinical data regarding the metabolic syndrome and surgical pathology of the patient were collected. The correlations between metabolic disorders (hypertension, hyperglycemia, and obesity) and clinicopathological characteristics as well as survival after surgery were analyzed. The study included 246 patients with clinical IB1 cervical cancer, 111 (45.1%) of whom had at least one of the comorbidities of hypertension, obesity, or hyperglycemia. Hypertension was positively correlated with parametrial invasion and poorly differentiated histology; hyperglycemia was positively correlated with stromal invasion; obesity was negatively associated with lymph node metastasis; but arbitrary disorder did not show any correlation with pathologic features. Hypertension was an independent risk factor for parametrial invasion (OR=6.54, 95% CI: 1.60-26.69); hyperglycemia was an independent risk factor for stromal invasion (OR=2.05, 95% CI: 1.07-3.95); and obesity was an independent protective factor for lymph node metastasis (OR=0.07, 95% CI: 0.01-0.60). Moreover, the patients with hypertension had a significantly lower 5-year OS rate (70.0% vs. 95.3%, P<0.0001) and a significantly lower 5-year PFS rate than those without hypertension (70.0% vs. 91.2%, P=0.010). Hypertension and hyperglycemia are positively associated with local invasion of early cervical cancer, which need to be verified in multi-center, large scale studies.

Obesity and comorbidities in COVID-19: a longitudinal observational retrospective study of the main relationships of life risk

Introduction: Currently, around 30% of the world's population is overweight or obese. By 2030, it is estimated that more than 60% of the world's population will be overweight or obese. The COVID19 pandemic has resulted in the worsening of obesity comorbidities. The primary increase in the inflammatory response in obese patients functions as a predictor for the hyperinflammatory state observed in COVID-19. Therefore, this primary increase can be amplified by SARS-CoV-2 infection, increasing the production of cytokines such as TNF-α, IL-1, and IL-6. Objective: It was to carry out a retrospective longitudinal observational study to quantitatively analyze how cardiovascular comorbidities such as diabetes, hypertension, obesity, smoking, and compromised immunity contribute to the increased risk of life of participants affected by COVID-19. Methods: This study followed a longitudinal observational retrospective design (STROBE). A total of 45 public and official documents from Brazil (ANVISA), WHO (World Health Organization), Pan American Health Organization (PAHO), EASO (The European Association for the Study of Obesity - The European Commission/ National Information on COVID-19, Lancet Resource Centre) and scientific articles were subjected to eligibility analysis and, after that, 32 documents dated from 2019 to 2022 were selected. Results: In total, 3,993,857 participants were found from 32 documents. The highest incidence of deaths occurred in participants who were smokers, had compromised immunity, had diabetes, and were obese. The greatest risk of death was observed among participants who smoke (HR=2.5) and those with compromised immunity (HR=2.1). Despite this, other comorbidities such as diabetes, obesity, and hypertension also presented statistically significant results for the risk of life. It was observed that only the difference between the means of the comorbidities “obesity” and “diabetes” was not statistically significant, with p&lt;0.05, that is, both comorbidities have similar impacts on the worsening and death of participants in the presence of COVID-19. Conclusion: Cardiovascular comorbidities such as diabetes, hypertension, obesity, smoking, and compromised immunity contributed to the increased risk of life in participants affected by COVID-19, especially in those of an older age. The endothelial dysfunction caused by SARS-CoV-2 explains why participants with comorbidities related to blood vessels such as cardiovascular disease, hypertension, diabetes, and obesity are more likely to develop severe COVID-19, even death

Retinol-Binding Protein 4 and Visfatin Levels in Patients with Periodontitis and Obesity/Overweight: A Systematic Review and Meta-Analysis.

Prior studies demonstrated an equivocal conclusion about the association between the level of retinol-binding protein 4 (RBP4)/visfatin and periodontitis patients with obesity. The aim of our study (Prospero ID: CRD42023469058) was to systematically review the available articles linking the biofluid levels of RBP4/visfatin to the comorbidity of periodontitis and obesity. Clinical trials were screened in accordance with specific inclusion criteria from seven databases up to November 2023. A quality assessment was performed with the Newcastle-Ottawa Scale and ROBINS-I tools for observational and interventional trials, respectively. The standard mean difference (SMD) with a 95% confidence interval (CI) related to the RBP4 level was recorded; the other indicators related to the visfatin level were measured via the mean difference (MD) with the corresponding 95% CI, and Fisher's Z transformation was measured to reveal the association using Review Manager 5.4. The current evidence was based on five observational studies and two interventional studies. All of them were included in the systematic review, and six of them were in the meta-analysis. Statistical analysis indicated that there was no significant difference in the circulating levels of RBP4 in the periodontitis patients with obesity or without, who were labeled as OP or NP, respectively (155 OP-107 NP: SMD = 1.38; 95% CI: -0.18-2.94, p = 0.08), as well as the periodontal healthy patients with a normal weight, who were labelled as NnP (116 OP-79 NnP: SMD = 6.76; 95% CI: -5.34-18.87, p = 0.27). Meanwhile, a significant higher level of serum visfatin was found in the OP patients than that of the NP (86 OP-45 NP: MD = 4.21; 95% CI: 2.65-5.77, p < 0.00001)/NnP (164 OP-88 NnP: MD = 13.02; 95% CI: 7.34-18.70, p < 0.00001) group. In addition, a positive association was observed between the serum RBP4 and body mass index/clinical attachment loss (CAL). And, then, there was a positive association between the serum visfatin and periodontal parameters, including the probing depth, CAL, and plaque index, as well as metabolic parameters, including the total cholesterol, triglycerides, fasting blood glucose, and low-density lipoprotein cholesterol. Here, the circulating RBP4 level was not independently related to the comorbidity of periodontitis and obesity, while serum visfatin was significantly associated with periodontitis and obesity. Notably, the positive association between circulating RBP4/visfatin and the periodontal parameters/metabolic parameters firmly suggested that the higher severity of the obese or periodontal status was associated with an elevated level of serum visfatin or RBP4 in the OP group. With more rigorous longitudinal research, the exact causations between RBP4/visfatin and the patients affected by obesity and periodontitis could be disentangled. RBP4 and visfatin might be novel, enlightening prospective bio-indexes for the targeted treatment of comorbidities.

Metabolomic Profiling of Obese Patients with Altered Intestinal Permeability Undergoing a Very Low-Calorie Ketogenic Diet.

A healthy intestinal permeability facilitates the selective transport of nutrients, metabolites, water, and bacterial products, involving cellular, neural, hormonal, and immune factors. An altered intestinal permeability indicates pathologic phenotypes and is associated with the exacerbation of obesity and related comorbidities. To investigate the impact of altered permeability in obese patients undergoing a calorie-restrictive dietary regimen (VLCKD), we collected urinary and fecal samples from obese patients with both normal and altered permeability (determined based on the lactulose/mannitol ratio) before and after treatment. The analysis of volatile organic compounds (VOCs) aids in understanding the metabolites produced by the intestinal microbiota in this unique ecological niche. Furthermore, we examined clinical and anthropometric variables from the cohort and compared them to significant VOC panels. Consequently, we identified specific markers in the metabolomics data that differentiated between normal and altered profiles before and after the diet. These markers indicated how the variable contribution specifically accounted for interleukins and lipopolysaccharides (LPS). The targeted metabolomics experiment detected no differences in measured short-chain fatty acids (SCFA). In summary, our study evaluated metabolomic markers capable of distinguishing low-grade inflammation conditions, exacerbated in more advanced stages of obesity with altered intestinal permeability.

Periodontitis and Metabolic Syndrome: Statistical and Machine Learning Analytics of a Nationwide Study.

This study aimed to analyze the associations between periodontitis and metabolic syndrome (MetS) components and related conditions while controlling for sociodemographics, health behaviors, and caries levels among young and middle-aged adults. We analyzed data from the Dental, Oral, and Medical Epidemiological (DOME) record-based cross-sectional study that combines comprehensive sociodemographic, medical, and dental databases of a nationally representative sample of military personnel. The research consisted of 57,496 records of patients, and the prevalence of periodontitis was 9.79% (5630/57,496). The following parameters retained a significant positive association with subsequent periodontitis multivariate analysis (from the highest to the lowest OR (odds ratio)): brushing teeth (OR = 2.985 (2.739-3.257)), obstructive sleep apnea (OSA) (OR = 2.188 (1.545-3.105)), cariogenic diet consumption (OR = 1.652 (1.536-1.776)), non-alcoholic fatty liver disease (NAFLD) (OR = 1.483 (1.171-1.879)), smoking (OR = 1.176 (1.047-1.322)), and age (OR = 1.040 (1.035-1.046)). The following parameters retained a significant negative association (protective effect) with periodontitis in the multivariate analysis (from the highest to the lowest OR): the mean number of decayed teeth (OR = 0.980 (0.970-0.991)); North America as the birth country compared to native Israelis (OR = 0.775 (0.608-0.988)); urban non-Jewish (OR = 0.442 (0.280-0.698)); and urban Jewish (OR = 0.395 (0.251-0.620)) compared to the rural locality of residence. Feature importance analysis using the eXtreme Gradient Boosting (XGBoost) machine learning algorithm with periodontitis as the target variable ranked obesity, OSA, and NAFLD as the most important systemic conditions in the model. We identified a profile of the "patient vulnerable to periodontitis" characterized by older age, rural residency, smoking, brushing teeth, cariogenic diet, comorbidities of obesity, OSA and NAFLD, and fewer untreated decayed teeth. North American-born individuals had a lower prevalence of periodontitis than native Israelis. This study emphasizes the holistic view of the MetS cluster and explores less-investigated MetS-related conditions in the context of periodontitis. A comprehensive assessment of disease risk factors is crucial to target high-risk populations for periodontitis and MetS.

Randomised, placebo-controlled, double-blinded trial of fecal microbiota transplantation in severe obesity: a study protocol

IntroductionObesity is one of the main threats to public health in western countries and increases the risk of several diseases, overall morbidity and mortality. Sustained weight loss will reduce risk...

Roux-en-Y gastric bypass and sleeve gastrectomy as revisional bariatric procedures after adjustable gastric banding: a retrospective cohort study

IntroductionThe frequency of revisional bariatric surgery is increasing, but its effectiveness and safety are not yet fully established. The aim of our study was to compare short-term outcomes of primary (pRYGB and pSG) and revisional bariatric surgeries (rRYGB and rSG).MethodsWe performed a retrospective cohort study assessing all patients submitted to primary and revisional (after a failed AGB) RYGB and SG in 2019. Each patient was followed-up at 6 months and 12 months after surgery. We compared pRYGB vs. rRYGB, pSG vs. rSG and rRYGB vs. rSG on weight loss, surgical complications, and resolution of comorbidities.ResultsWe assessed 494 patients, of which 18.8% had undergone a revisional procedure. Higher weight loss at 6 and 12 months was observed in patients undergoing primary vs. revisional procedures. Patients submitted to rRYGB lost more weight than those with rSG (%EWL 12 months = 82.6% vs. 69.0%, p < 0.001). Regarding the resolution of obesity-related comorbidities, diabetes resolution was more frequent in pRYGB than rRYGB (54.2% vs. 25.0%; p = 0.038). Also, 41.7% of the patients who underwent rRYGB had dyslipidemia resolution vs. 0% from the rSG group (p = 0.035). Dyslipidemia resolution was also more common in pSG vs. rSG (68.6% vs. 0.0%; p = 0.001). No significant differences in surgical complications were found.ConclusionRevisional bariatric surgery is effective and safe treating obesity and related comorbidities after AGB. Primary procedures appear to be associated with better weight loss outcomes. Further prospective studies are needed to better understand the role of revisional bariatric surgery.

Anesthesia for Morbidly Obese Patients.

The prevalence of morbid obesity (BMI >35 kg/m2) has risen steadily in recent decades. With the corresponding rise in the number of bariatric operations, anesthesiologists deal with this patient group more commonly than before, particularly in specialized centers. This review is based on publications retrieved by a selective search in PubMed, including current guidelines and recommendations issued by specialist societies, as well as expert opinion. In the anesthesiological care of morbidly obese patients, a preoperative assessment and risk stratification are just as important as the thoughtful selection of the anesthesia technique, the drugs used and their dosage, and perioperative management. A thorough understanding of the pathophysiological changes and comorbidities of morbid obesity and the associated risks is essential. The risk of pulmonary complications such as respiratory failure, hypoxia, and apnea is markedly higher in morbidly obese patients, especially those with obstructive sleep apnea. Short-acting, less lipophilic anesthetic drugs are particularly useful, as is multimodal pain therapy for the avoidance of high opiate doses. The indication for intensified postoperative monitoring depends on the patient's preexisting illnesses, the type of anesthesia, and the type of surgical procedure. Regional anesthetic techniques should be used if possible. The perioperative care of morbidly obese patients presents special challenges. The anesthesiologist must be aware of potential comorbidities, specific risks, and pathophysiological changes in order to provide adequate care to this patient group.

Comparative Clinical Effects and Risk Factors Associated With Vitamin D in Foot and Ankle Fracture and Arthrodesis Healing

Vitamin D deficiency in relation to bone metabolism and healing has been controversial and not well studied. However, hypovitaminosis has been widely identified within the orthopedic patient population. The current best evidence suggests a lack of data on this important topic. The ability to assess patients for optimum bone healing and metabolism is still in question due to lack of a suitable reliable biomarker and multiple other unknown variables affecting bone metabolism. To compound this effect, popular dermatological precautions in the last 20 to 30 years of avoiding sunlight also have the effect of further reducing serum vitamin D production in the skin. As a proof of concept, we performed a preliminary comparative observational retrospective review of orthopedic patients undergoing fracture and arthrodesis osseous healing to determine how serum vitamin D levels are associated with bone healing along with their confounding comorbidities. Based on our review, the current accepted vitamin D levels (≥20 ng/mL) are low and insufficient for fractures and for arthrodesis osseous healing due to observed high rates (>35%) of delayed unions, and an increased (>90%) in the number of multiple confounding comorbidities affecting bone healing process that are often not mentioned or captured in this type of study in previous literature. Obesity and diabetes are significant contributory risks factors, and the preliminary findings suggest that the current accepted adequate levels may not be enough for osseous healing. These low vitamin D levels appear to affect bone healing and prolong treatment, with worsening trends with diabetes and obesity comorbidities.

Racial Disparities in Hospital Outcomes of Autologous Stem Cell Transplantation for Multiple Myeloma: A Comparative NIS 2016 to 2020 Database Study

Objective: Due to the paucity of data and the difference in-hospital outcomes in the two most common races in America remains controversial. This study aims to compare hospital outcomes in multiple myeloma patients undergoing autologous stem cell transplantation (ASCT) between White and Black patients using data from the National Inpatient Sample (NIS) from 2016 to 2020. Methods: A retrospective analysis of the NIS database was conducted using International Classification of Diseases (ICD-10) codes to identify patients who underwent ASCT for multiple myeloma. STATA version MP14.2 was used for analysis. We used Fischer's exact test to compare proportions, the student's t-test to compare continuous variables, and multivariate regression analysis to calculate the adjusted odds ratio after controlling age, gender, primary payer, and CCI. Following are included in transplant complications (transplant rejection, failure, transplant infection). Results: Among 31,389 hospitalizations, 19,065 (60.74%) were whites, and 6,110 (19.47%) were blacks. The mean age was 62 in whites and 59 in blacks (P &amp;lt; 0.001). Most patients were male, constituting 59.46% among Whites and 71.11% among Blacks. A significantly higher proportion of blacks had comorbidities compared to whites, including CKD (18.9% vs. 14.98%), diabetes mellitus (25.94% vs. 14.29%), obesity (16.35% vs. 11.6%), and mean Charlson Comorbidity Index (2.51 vs. 2.42, P &amp;lt; 0.001). On multivariate analysis compared to whites, blacks had a non-significant difference in the risk of acute kidney injury (adjusted odds ratio [AOR]: 0.94, 95% confidence interval [CI]: 0.76-1.17, P =0.58), cardiac arrest (AOR: 0.71, 95% CI: 0.16-3.20, P = 0.71), and blood transfusion (AOR: 1.11, 95% CI: 0.89-1.37, P = 0.36). Additionally, there was no significant difference in the average length (16.53 vs. 16.52, P = 0.85) and total cost ($195,971 vs. $196,300, P = 0.76) of hospital stay between blacks and whites. However, blacks had significantly lower transplant complications (AOR: 0.56, 95% CI: 0.37-0.87, P = 0.01), ICU admission (AOR: 0.58, 95% CI: 0.35-0.97, P = 0.04) and in-hospital mortality (AOR: 0.28, 95% CI: 0.09-0.91, P = 0.03) compared to whites. Conclusion: According to our study, blacks who underwent ASCT for multiple myeloma had better outcomes than Whites. Despite having a higher mean age and more comorbidities, this finding emphasizes the importance of conducting additional research and providing personalized interventions to enhance patient outcomes. It also suggests the potential for more black Americans to undergo ASTCT and benefit from it while avoiding delays and improving overall survival rates.

Inclusion of Subjects who are Obese in Drug Development: Current Status and Opportunities.

The prevalence of obesity has grown tremendously in recent years and this population has an increased risk of disease comorbidities. The presence of disease comorbidities requires treatment interventions and proper dosing guidelines. However, drug development programs often do not have adequate representation of individuals who are obese in clinical trials, leaving gaps in the understanding of treatment response leading to a lack of adequate individualization options. Based on a recent survey of approved drug product package inserts, very few approved products included specific dosing based on obesity, in both adults and pediatrics. Reasons for the limited information on patients who are obese may include the under-reporting of information regarding such patients and a lack of clinical trial diversity in enrolling patient groups in whom obesity or obesity-related comorbidities are more prevalent. An inadvertent impact of the practice of exclusion of subsets of patients with some comorbidities in clinical trials may play a role in the reduced enrollment of individuals who are obese. Recently, regulatory authorities have taken specific initiatives to promote clinical trial diversity, including engaging with stakeholders and publishing regulatory guidance. These guidance documents highlight the need to enroll diverse clinical trial populations and provide recommendations on concepts related to drug development for obese populations. Such efforts will help to address the gap in information regarding drug response and dosing in patients who are obese.

Impact of Bariatric Surgery on Patients' Satisfaction and Quality of Life: A Narrative Review

Context: Obesity is a significant health issue that has been considered an epidemic in the world during the last 20 years and has persistently increased over time. The World Health Organization recently reported that the worldwide prevalence of overweight among adults was more than 1.9 billion, and approximately 650 million adults were obese. Bariatric surgery remains the most successful and effective long-term option for treating morbid obesity and obesity-related co-morbidities due to the significant outcomes in long-term weight loss, resolution of obesity-related co-morbidities, reduction of cardiovascular complications, and the causes of obesity-related mortality.&#x0D; Aim: This review sought to provide a comprehensive and critical summary of existing literature on the impact of bariatric surgery on patients’ satisfaction and quality of life.&#x0D; Methods: A systematic search was undertaken between 2018 and 2022 with specific inclusion criteria. Search terms were determined to select the best relevant studies using a wide search in different databases, including PubMed, Medline, EBSCO, EBMR, and ERIC. The review used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to identify the literature used in this review. The review identified fifty studies that met the eligibility criteria and were involved in this review.&#x0D; Results: The result indicates that quality of life was improved in most of the studies after the different types of bariatric surgeries. Also, the satisfaction level was high in most of the retrieved studies. Besides, all co-morbidities associated with obesity were reduced significantly.&#x0D; Conclusion: The findings demonstrate that each surgical procedure has negative and positive outcomes. The finding also recognized the impact of bariatric surgery in improving the patients' satisfaction, enhancing their quality of life, and remission of obesity-related co-morbidity diseases. Bariatric surgery is strongly suggested in the treatment of morbidly obese patients.

Comorbidities in women with polycystic ovary syndrome: a sibling study

Abstract Background Polycystic ovary syndrome (PCOS) has previously been associated with several comorbidities that may have shared genetic, epigenetic, developmental or environmental origins. We analyzed the association between PCOS and several relevant comorbidities while adjusting for early-life biological and socioeconomic conditions, also investigating the extent to which the association is affected by familial risk factors. Methods This total-population register-based cohort study included 857,757 singleton females (333,999 with at least one full sister) born between 1962 and 1980. PCOS and comorbidity diagnoses were measured at age 17-45 years through national hospital register data from 1997 to 2011, and complemented with information on the study subjectś early-life and social characteristics. In the main analysis, sibling fixed effects (FE) models were used to control for all factors that are shared and time-invariant among sisters, thereby testing whether PCOS and examined comorbidities are determined by unobserved familial; environmental, social or genetic factors. Results 9,321 women were diagnosed with PCOS, of whom 15% had obesity, 9% had depression, 8% had anxiety and 4% suffered from sleeping, sexual and eating disorders (SSE). Having PCOS was associated with the odds of obesity increasing nearly 6-fold (adjusted OR (aOR): 5.8 [95%CI:5.5-6.2]). This association was attenuated considerably when accounting for characteristics shared between full sisters (Sister FE: aOR: 4.5 [95% CI: 3.6-5.6]). Among the psychiatric comorbidities, depression (Sister FE: aOR: 1.4 [95% CI: 1.2-1.8]) and anxiety (Sister FE: aOR: 1.5 [95% CI: 1.2-1.8), there was a small decrease in the aORs when also controlling for factors shared between sisters. Conclusions Having been diagnosed with PCOS is associated with an increased risk of obesity and psychiatric comorbidities and a substantial part of this risk can be attributed to factors shared between sisters. Key messages • PCOS is associated with an increased risk of obesity, depression and anxiety. • Among women with PCOS, 16% of the increased risk for obesity, 20% for depression and 29% for anxiety can be attributed to shared family factors between sisters.

Development and Piloting of the Enhanced Integrated Behavioral Model to Frame a Social Marketing Campaigns for Teens

Background Teenagers are at high-risk of obesity and related co-morbidities, and yet, are notoriously challenging to engage for behavior change. Focus This work offers an innovative integrated theoretical model, the Enhanced Integrated Behavioral Model (EIBM), drawing from communication, persuasion, and behavior-change theories to inform social marketing. Research Question Can the EIBM prove effective to reach and engage teens in both behavior- and social norms-change? Program Design/Approach We used EIBM to pilot a social marketing campaign aimed at increasing water consumption among teens and their networks. Importance to Field Social marketing is an approach, not a theory. Behavior change models usually provide only limited instruction on messaging. Communication theories can lack practical application guidance. By combining both, we propose a theoretical framework to maximize social marketing campaigns. Methods We piloted a two-tiered social media driven social marketing campaign for high school students to promote increased water consumption and decreased sugar-sweetened beverage consumption in rural New Mexico to change their behaviors and engage them as change agents. Results Our campaign guided students through various stages of attitude, empowerment, and behavior change, for themselves and their families and friends, supporting our model’s utility for social marketing campaign design and implementation. Recommendations for Research Further testing of EIBM for social marketing.

Diet-induced obesity and diabetes enhance mortality and reduce vaccine efficacy for SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a wide spectrum of diseases in the human population, from asymptomatic infections to death. It is important to study the host differences that may alter the pathogenesis of this virus. One clinical finding in coronavirus disease 2019 (COVID-19) patients is that people with obesity or diabetes are at increased risk of severe illness from SARS-CoV-2 infection. We used a high-fat diet model in mice to study the effects of obesity and type 2 diabetes on SARS-CoV-2 infection as well as how these comorbidities alter the response to vaccination. We find that diabetic/obese mice have increased disease after SARS-CoV-2 infection and they have slower clearance of the virus. We find that the lungs of these mice have increased neutrophils and that removing these neutrophils protects diabetic/obese mice from disease. This demonstrates why these diseases have increased risk of severe disease and suggests specific interventions upon infection.

Physical activity in the new era of antiobesity medications.

Contemporary antiobesity medications (AOMs) are highly efficacious for the treatment of obesity and obesity-related comorbidities. Given this effectiveness, lifestyle factors within the context of AOM treatments need to refocus and move away from efforts to enhance weight loss. Rather, lifestyle considerations should pivot to being complementary to the benefits realized with AOM treatment and be redirected to enhancing holistic patient health and well-being. Physical activity is an important lifestyle behavior that contributes to many health benefits both in conjunction with, and in the absence of, weight loss. Physical activity improves cardiorespiratory fitness, muscle strength, and physical function. Physical activity may attenuate the loss of lean mass that is observed with AOM treatments and may enhance the quality and function of muscle. Physical activity is a key behavior for holistic health within this era of contemporary AOMs that warrants appropriate attention within the clinical care of patients.

Guselkumab-Treated Patients with Plaque Psoriasis Who Achieved Complete Skin Clearance for ≥156 Consecutive Weeks: A Post-Hoc Analysis From the VOYAGE 1 Clinical Trial.

Treatment of moderate-to-severe plaque psoriasis with biologics, such as guselkumab, has demonstrated greater efficacy over traditional non-biologic treatments. However, given patient diversity, greater understanding of the relationship between patient characteristics, positive clinical outcomes, and long-term response to biologics is crucial for optimizing treatment choices. This post-hoc analysis of the 5-year VOYAGE1 clinical trial compares baseline characteristics of patients maintaining a Psoriasis Area and Severity Index (PASI) score of 0 at all visits for ≥156 consecutive weeks (PASI=0 group) with those that never achieve PASI=0 (comparator group), using descriptive statistics and a multiple logistic regression model. Guselkumab plasma trough concentrations in both response groups were assessed from Weeks 4-156. Of patients who started guselkumab treatment at Week 0 or at Week 16 after switching from placebo, 22.7% (112/494) maintained PASI = 0 for ≥156consecutive weeks. Numerical differences in baseline characteristics, including age, obesity, diabetes, PASI score, disease duration, smoking status, and psoriatic arthritis comorbidity, were identified between the PASI = 0 group and comparator group. Plasma guselkumab levels were consistently higher in the PASI = 0 group. Multiple logistic regression analysis revealed absence of diabetes, lower Dermatology Life Quality Index score at baseline, and higher Week 4 guselkumab plasma concentration as significantly (p<0.05) associated with the PASI = 0 group. A substantial (22.7%) number of guselkumab-treated patients in the VOYAGE 1 clinical trial maintained complete skin clearance for a consecutive period of ≥156 weeks. Factors associated with this outcome may suggest clinical benefits of holistic treatment approaches. NCT02207231.

THU628 Causal Relationship Between The Menstrual Cycle Length And Basal Metabolic Rate: A Two-sample Mendelian Randomization Study

Abstract Disclosure: M. Kazemi: None. S.A. Parry: None. Long or irregular menstrual cycles, as a hallmark reproductive trait in polycystic ovary syndrome (PCOS), have been associated with aberrant energy expenditure, obesity, and cardiometabolic comorbidities. However, current observational studies addressing the contributions of energy expenditure to menstrual cyclicity have generated conflicting results and have not utilized the full extent of known single nucleotide polymorphisms associated with basal energy expenditure. Whether the relationship is causal is uncertain. We conducted a two-sample Mendelian Randomization study to interrogate the causal relationships between basal metabolic rate and length of menstrual cycles. The (MR) analyses were performed using publicly released genome-wide association studies (GWAS) statistics from 2 separate European cohorts using the UK Biobank database. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), to detect and correct the effect of horizontal pleiotropy. The result of the IVM method revealed that genetically determined basal metabolic rate has an inverse causal effect on the length of the menstrual cycle (β, -0.13, SE, 0.03; P=2.17 E-05). The results of MR-Egger regression, weighted median, and weighted mode methods were consistent with those of the IVW method. Sensitivity analyses revealed that horizontal pleiotropy was unlikely to distort the causal estimates. Collectively, our MR analysis revealed that basal metabolic rate appears to be causally affecting the length of menstrual cycles. Our findings reflect novel insights into the role of energy metabolism on menstrual disturbances. However, the molecular mechanisms should be investigated. Future MR analysis is warranted to confirm our findings by controlling for potentially relevant confounders, including obesity and age. Nevertheless, our findings have perturbations to elucidate causal pathways explaining obesity in relevant conditions, including PCOS. Presentation: Thursday, June 15, 2023

SAT275 Generation And Characterization Of A Humanized CYP21A2 Mouse Model For Congenital Adrenal Hyperplasia

Abstract Disclosure: A. Huebner: None. S. Thirumalasetty: None. T. Schubert: None. R. Naumann: None. I. Reichardt: None. M. Rohm: None. D. Landgraf: None. F. Gembardt: None. M.F. Hartmann: None. S.A. Wudy: None. M. Peitzsch: None. N. Reisch: None. K. Koehler, PhD: None. 21-hydroxylase deficiency (21OHD) is the most common form of congenital adrenal hyperplasia (CAH) and is caused by mutations in the CYP21A2 gene. 21OHD causes a wide array of clinical symptoms that result from gluco- and mineralocorticoid deficiency and adrenal androgen excess. Treatment firstly aims to substitute lacking steroid hormones, and secondly to restore negative feedback towards CRH and pituitary ACTH secretion to diminish adrenal androgen overproduction. In most cases supra-physiological glucocorticoid doses are necessary which may cause short stature, obesity, hypertension, and cardiovascular and metabolic co-morbidity with reduced quality of life. Hence, current steroid substitution regimens have significant limitations, so novel therapeutic strategies are required. In recent years new therapeutic approaches have emerged including new non-glucocorticoid substances interfering with the HPA axis to minimize adrenal androgen production and to lower external glucocorticoid substitution to physiological levels. However, valuable in-vivo models for pre-clinical testing of such drugs are lacking. Here we present the first viable and humanized mouse model in which the mouse gene Cyp21a1 is replaced by the human orthologue CYP21A2 in which the human point mutation R484Q is integrated. Twenty-weeks-old homozygous mice show marked adrenal hyperplasia, enhanced expression of the CYP21A2 gene and a weak increase of Cyp11a1 and Cyp11b2 gene expression. Tandem mass spectrometry measurements of the mice plasma at 20 weeks show decreased corticosterone and 11-deoxycorticosterone levels in the presence of increased ACTH levels in both male and female homozygous animals. Progesterone levels in homozygous mice are significantly higher (p&amp;lt;0.01) than in wildtype mice. We also observed increased aldosterone levels in female mutants whereas blood pressure does not differ between wildtype and mutant mice strains. Histologically, mutants exhibit adrenocortical hyperplasia. While mutant male mice are fertile with normal appearing testes, females are infertile, remain in the diestrus phase and present with a reduced number of ovarian follicles. In parallel, a second mouse strain bearing the I173N mutation was developed. This mutation is frequent in human patients causing simple virilizing or rarely salt wasting CAH. Homozygous mice require dexamethasone treatment during pregnancy and until weaning but are viable without treatment afterwards. Preliminary results show adrenal hyperplasia and alteration in steroidogenic gene expression and steroid profiles. In conclusion, we demonstrate that the humanized mutant CYP21A2 mice may represent an excellent animal CAH model to test novel treatment strategies for CAH patients. We believe that this model(s) will facilitate the transition from basic research into clinical application. Presentation: Saturday, June 17, 2023