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1.
Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes.
Yang, J, Yang, X, Wu, G, Huang, F, Shi, X, Wei, W, Zhang, Y, Zhang, H, Cheng, L, Yu, L, et al
Cell metabolism. 2023;35(9):1548-1562.e7
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Distal symmetric polyneuropathy (DSPN) is the most common complication associated with diabetes, which can lead to pain, numbness, and weakness or tingling in the limbs or parts of the body. There are no cures for DSPN only drugs to manage symptoms, highlighting a need for further research. Recently it has been shown that the gut microbiota of individuals with DSPN differs to that of healthy individuals, but it is unclear as to the significance of this. This randomised control trial aimed to determine the effect of transplanting faecal microbiota from healthy individuals into those with DSPN. The results showed that DSPN was associated with a decreased abundance of beneficial gut bacteria and an increased abundance of pathogenic bacteria. Furthermore, compared to placebo, DSPN was alleviated in all 22 patients who received a faecal microbiota transplant from healthy subjects. There was an increase in gut microbiota associated with the production of beneficial short chain fatty acids and a decrease in toxin production. It was concluded that dysbiosis in the gut microbiota contributes to DSPN, which can be alleviated by faecal microbial transplant from healthy individuals. This study could be used by healthcare professionals to understand that the gut microbiota has an important role in DSPN. Further larger studies would be warranted before recommending faecal microbial transplant to individuals with this disorder.
Abstract
The pathogenic mechanisms underlying distal symmetric polyneuropathy (DSPN), a common neuropathy in patients with diabetes mellitus (DM), are not fully understood. Here, we discover that the gut microbiota from patients with DSPN can induce a phenotype exhibiting more severe peripheral neuropathy in db/db mice. In a randomized, double-blind, and placebo-controlled trial (ChiCTR1800017257), compared to 10 patients who received placebo, DSPN was significantly alleviated in the 22 patients who received fecal microbiota transplants from healthy donors, independent of glycemic control. The gut bacterial genomes that correlated with the Toronto Clinical Scoring System (TCSS) score were organized in two competing guilds. Increased guild 1, which had higher capacity in butyrate production, and decreased guild 2, which harbored more genes in synthetic pathway of endotoxin, were associated with improved gut barrier integrity and decreased proinflammatory cytokine levels. Moreover, matched enterotype between transplants and recipients showed better therapeutic efficacy with more enriched guild 1 and suppressed guild 2. Thus, changes in these two competing guilds may play a causative role in DSPN and have the potential for therapeutic targeting.
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Age-Dependent Relationships Between Disease Risk and Testosterone Levels: Relevance to COVID-19 Disease.
Muehlenbein, M, Gassen, J, Nowak, T, Henderson, A, Morris, B, Weaver, S, Baker, E
American journal of men's health. 2023;17(2):15579883221130195
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A growing body of research finds that in men, testosterone levels may be prognostic of clinical outcomes related to coronavirus disease 2019 (COVID-19 disease). The presence of pre-existing chronic conditions in many patients with COVID-19 disease further complicates the relationship among testosterone and severe outcomes. The aim of this study was to examine whether pre-existing conditions for severe COVID-19 disease were related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. This study obtained data from men (n = 142) who participated in the longitudinal study Waco COVID Survey. All data included in the study was collected as part of the initial intake survey and first laboratory appointment. Results show that serum-free testosterone levels decreased as a function of age. In fact, greater burden of pre-existing conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. Furthermore, in men older than 40 years of age the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Authors conclude that their findings add important insights into the complex role of androgens in chronic and infectious diseases and contribute to the growing body of literature on the relationship between chronic disease and men’s testosterone levels.
Abstract
Testosterone levels in men appear to be prognostic of a number of disease outcomes, including severe COVID-19 disease. Testosterone levels naturally decline with age and are lower in individuals with a number of comorbidities and chronic conditions. Low testosterone may therefore be both a cause and a consequence of illness, including COVID-19 disease. The present project examines whether preexisting conditions for severe COVID-19 disease were themselves related to serum-free testosterone levels in men who had not been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. A clinical risk score for severe COVID-19 disease was computed based on the results of previously published meta-analyses and cohort studies, and relationships between this score and testosterone levels were tested in 142 men ages 19 to 82 years. Greater burden of preexisting conditions for severe COVID-19 disease was related to lower testosterone levels among men younger than 40 years of age. In older men, the decrease in testosterone that accompanies aging attenuated the effect of the clinical risk score on free testosterone levels. Given that older age itself is a predictor of COVID-19 disease severity, these results together suggest that the presence of preexisting conditions may confound the relationship between testosterone levels and COVID-19 disease outcomes in men. Future research examining relationships among testosterone and outcomes related to infectious and chronic diseases should consider potential confounds, such as the role of preexisting conditions.
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Metabolic dysfunction-associated fatty liver disease and cardiovascular disease: A meta-analysis.
Wen, W, Li, H, Wang, C, Chen, C, Tang, J, Zhou, M, Hong, X, Cheng, Y, Wu, Q, Zhang, X, et al
Frontiers in endocrinology. 2022;13:934225
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Non-alcoholic fatty liver disease (NAFLD) is a multi-system disease that not only affects the structure and function of the liver but also increases the incidence of type 2 diabetes, cardiovascular disease (CVD), cerebrovascular disease, and chronic kidney disease. In 2020, experts reached a consensus to recommend a more appropriate term to more accurately and positively define fatty liver disease associated with metabolic disorders, namely, metabolic dysfunction-associated fatty liver disease (MAFLD). The aim of this study was to investigate the risk of CVD incidence or CVD mortality in patients diagnosed with MAFLD. This study is a meta-analysis of ten cohort studies. Results show that patients in the MAFLD group had a significantly increased relative risk of CVD or death from CVD during the follow-up compared with the control group. Authors conclude that even though there is a positive association between MAFLD and the risk of CVD or death from CVD, further studies are needed to demonstrate different effects of the newly defined MAFLD on CVD compared with previous NAFLD.
Abstract
BACKGROUND Metabolic dysfunction-associated fatty liver disease [MAFLD, formerly known as nonalcoholic fatty liver disease (NAFLD)] is one of the most important causes of liver disease worldwide, while cardiovascular disease (CVD) is still one of the main causes of morbidity and mortality worldwide, and the two are closely related. This study aimed to investigate the risk of CVD incidence or CVD-related mortality (CVD mortality) in patients diagnosed with MAFLD under new concepts and new diagnostic criteria. METHODS We searched English databases PubMed, Web of Science, Embase, and Cochrane Library for relevant literature. The language was restricted to English. RESULTS By 22 January 2022, 556 published studies were obtained through preliminary retrieval, and 10 cohort studies were included in this study. All statistical analyses were performed using Review Manager 5.2 software. Compared with the control group, patients in the MAFLD group had a significantly higher relative risk of CVD incidence or CVD mortality during the follow-up, with an RR rate of 1.95 (95% CI 1.76-2.17, p < 0.01). The incidence of CVD in the MAFLD group was more than twice that in the control group (RR 2.26, 95% CI 2.00-2.54, p < 0.01). The mortality rate of CVD was 1.57 times higher than that in the control group (RR 1.57, 95% CI 1.42-1.72, p < 0.01). CONCLUSIONS Patients diagnosed with MAFLD alone had higher cardiovascular mortality than those diagnosed with NAFLD alone based on the available data.
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Gut and Reproductive Tract Microbiota Adaptation during Pregnancy: New Insights for Pregnancy-Related Complications and Therapy.
Siena, M, Laterza, L, Matteo, MV, Mignini, I, Schepis, T, Rizzatti, G, Ianiro, G, Rinninella, E, Cintoni, M, Gasbarrini, A
Microorganisms. 2021;9(3)
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During pregnancy, several adaptations occur in the female organism. In fact, from fertilization until delivery, the maternal body changes and activates a series of physiological transformations to welcome the new life. The microbiota as a component of human bodies is subject to these modifications. This study is a review that focused on gut and reproductive tract microbiota variations during physiologic pregnancy and in case of pregnancy complications, particularly gestational diabetes mellitus (GDM), pre-eclampsia (PE), and preterm birth (PTB). Results show that: - during pregnancy, major changes have been seen in mothers’ gut microbiota. Between the first and third trimester of pregnancy, to support the foetus growth, there is a shift towards communities of microbes implicated in energy production and storage. - in nonpregnant women, vaginal microbiota could be classified into five major types, representing the community state types. - meconium’s microbes seems to be dominated by the Enterobacteriaceae family, suggesting prenatally stepwise colonization. - gut microbiota may contribute to enhanced insulin resistance in early pregnancy (1st and 2nd trimester). - microbiota imbalances in PE women are related not only with blood pressure levels but also with markers of kidney dysfunction. Thus, it is of key importance to understand the role of microbiota and other factors involved in the etiopathogenesis of PE - dysbiosis is related to PTB (however, further studies are necessary to better understand the correlation between this pregnancy complication and the specific microbiota alteration). Authors conclude that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
Abstract
Pregnancy is characterized by maternal adaptations that are necessary to create a welcoming and hospitable environment for the fetus. Studies have highlighted how the microbiota modulates several networks in humans through complex molecular interactions and how dysbiosis (defined as quantitative and qualitative alterations of the microbiota communities) is related to human pathologies including gynecological diseases. This review analyzed how maternal uterine, vaginal, and gut microbiomes could impact on fetus health during the gestational period. We evaluated the role of a dysbiotic microbiota in preterm birth, chorioamnionitis, gestational diabetes mellitus and pre-eclampsia. For many years it has been hypothesized that newborns were sterile organisms but in the past few years this paradigm has been questioned through the demonstration of the presence of microbes in the placenta and meconium. In the future, we should go deeper into the concept of in utero colonization to better understand the role of microbiota through the phases of pregnancy. Numerous studies in the literature have already showed interesting results regarding the role of microbiota in pregnancy. This evidence gives us the hope that microbiota modulation could be a novel strategy to reduce the morbidity and mortality related to pregnancy complications in the future.
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Implications of the vaginal microbiome and potential restorative strategies on maternal health: a narrative review.
Moumne, O, Hampe, ME, Montoya-Williams, D, Carson, TL, Neu, J, Francois, M, Rhoton-Vlasak, A, Lemas, DJ
Journal of perinatal medicine. 2021;49(4):402-411
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The vaginal microbiome is a complex community of bacteria that maintains and contributes to vaginal health and works together to protect the host from disease. Lactobacilli are the predominant species in a healthy vaginal microbiome. This review sought to summarize current evidence on how changes in the vaginal microbiome composition before and throughout pregnancy influence and contribute to several health conditions. The authors investigated the role of the vaginal microbiome in fertility and in-vitro fertilization (IVF), where evidence is still conflicting, followed by conditions that can present during pregnancy such as preterm labour, gestational diabetes, and preeclampsia. In preterm labour, lower levels of Lactobacillus and its D-lactic acid secretions have been observed as a common denominator; in gestational diabetes, it remains unclear whether the changes in the vaginal microbiome associated with the condition are causative or rather a result of the condition. Little research has been done regarding preeclampsia, but initial studies indicate there may be a link between the condition and the vaginal microbiome. The authors also reviewed the evidence on methods of restoring vaginal health, including oral and vaginally applied probiotics as well as vaginal microbiome transplants (VMT) - the transfer of vaginal secretions from a healthy donor. The paper discusses the evidence on the use of oral and locally applied probiotics for the aforementioned conditions, and the promising potential of VMTs alongside the risks and regulatory challenges that come with it. This review provides a helpful summary of the current understanding of the role of the vaginal microbiome in fertility and throught pregnancy.
Abstract
The vaginal microbiome undergoes dramatic shifts before and throughout pregnancy. Although the genetic and environmental factors that regulate the vaginal microbiome have yet to be fully elucidated, high-throughput sequencing has provided an unprecedented opportunity to interrogate the vaginal microbiome as a potential source of next-generation therapeutics. Accumulating data demonstrates that vaginal health during pregnancy includes commensal bacteria such as Lactobacillus that serve to reduce pH and prevent pathogenic invasion. Vaginal microbes have been studied as contributors to several conditions occurring before and during pregnancy, and an emerging topic in women's health is finding ways to alter and restore the vaginal microbiome. Among these restorations, perhaps the most significant effect could be preterm labor (PTL) prevention. Since bacterial vaginosis (BV) is known to increase risk of PTL, and vaginal and oral probiotics are effective as supplemental treatments for BV prevention, a potential therapeutic benefit exists for pregnant women at risk of PTL. A new method of restoration, vaginal microbiome transplants (VMTs) involves transfer of one women's cervicovaginal secretions to another. New studies investigating recurrent BV will determine if VMTs can safely establish a healthy Lactobacillus-dominant vaginal microbiome. In most cases, caution must be taken in attributing a disease state and vaginal dysbiosis with a causal relationship, since the underlying reason for dysbiosis is usually unknown. This review focuses on the impact of vaginal microflora on maternal outcomes before and during pregnancy, including PTL, gestational diabetes, preeclampsia, and infertility. It then reviews the clinical evidence focused on vaginal restoration strategies, including VMTs.
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Association Between Prediabetes and Erectile Dysfunction: A Meta-Analysis.
Jin, M, Yuan, S, Wang, B, Yi, L, Wang, C
Frontiers in endocrinology. 2021;12:733434
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Erectile dysfunction (ED) is a common sexual dysfunction in men, which is defined as the failure to achieve or maintain an erection for satisfactory sexual intercourse. Besides aging, diabetes mellitus has also been recognised as a major risk factor for ED. The aim of this study was to systematically evaluate the association between prediabetes and ED. This study is a meta-analysis of nine observational studies, including five matched case-control studies and four cross-sectional studies. Results show that compared to men with normoglycemia, those with prediabetes were associated with higher prevalence of ED. Further subgroup analysis showed that mean age of the male participants in each study may affect the results as the association between prediabetes and ED seemed to be stronger in studies with younger men (mean age <50 years) than that in studies with older men (mean age ≥50 years). Authors conclude that prediabetes is associated with higher prevalence of ED, which may be independent of age of the males and may be stronger in young men.
Abstract
BACKGROUND Diabetes has been associated with the increased risk of erectile dysfunction (ED). However, previous studies evaluating the association between prediabetes and ED showed inconsistent results. We performed a meta-analysis of observational studies to systematically evaluate the above association. METHODS Relevant observational studies were retrieved by search of PubMed, Embase, and Web of Science databases. A random-effect model which incorporated the potential intra-study heterogeneity was used for the meta-analysis. Subgroup analyses were performed to evaluate the influences of study characteristics on the outcome. RESULTS Nine studies (five matched case-control studies and four cross-sectional studies) were included. Age were adjusted or matched in all of the studies. Pooled results showed that compared to men with normoglycemia, men with prediabetes were associated with higher prevalence of ED (odds ratio = 1.62, 95% confidence interval: 1.28 to 2.07, P < 0.001; I2 = 78%). Subgroup analyses showed that the association was not significantly affected by definition of prediabetes, diagnostic tool for ED, or controlling of additional variables besides age (both P for subgroup difference > 0.05). However, the association between prediabetes and ED seemed to be stronger in case-control studies than that in cross-sectional studies, and in studies with younger men (mean age < 50 years) than in those with older men (mean age ≥ 50 years; both P for subgroup difference < 0.05). CONCLUSIONS Prediabetes is associated with higher prevalence of ED, which may be independent of age of the males and may be stronger in young men.
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Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism.
Scheele, C, Wolfrum, C
Endocrine reviews. 2020;41(1)
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Brown adipose tissue (BAT) is an important contributor to the regulation of metabolism via cellular communication with organs such as liver, muscle, gut and central nervous system. BAT is important for heat generation and is at high levels in human infants. Levels of activation of BAT decline as we age and it has been shown that the amount of BAT is smaller and its activity reduced in those with obesity and type 2 diabetes. To date, there is no answer to efficiently restore functional BAT in aging and obese subjects. This review looks at experiments done on the factors secreted from active BAT (batokines). The review aims to provide a structure for the processes and cell types involved in BAT and the recent findings of BAT whole-body communication are discussed. Altogether, these findings demonstrate that BAT has an adaptive capacity. Studying batokines, offers an alternative approach to identify novel drug targets for metabolic regulation.
Abstract
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX - XXX, 2020).
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Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults.
Ludvigsson, JF
Acta paediatrica (Oslo, Norway : 1992). 2020;109(6):1088-1095
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Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was also previously known as 2019-nCoV. This study is a systematic literature review which summarises the findings on the current knowledge of COVID-19 in children. The review includes 45 scientific papers and letters. Results showed that children have so far accounted for 1%-5% of diagnosed cases. Children often are asymptomatic, have milder disease than adults, and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent. Authors conclude that the disease course in paediatric COVID-19 was milder than in adults, children had a better prognosis and deaths were extremely rare.
Abstract
AIM: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS A systematic literature review was carried out to identify papers on COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%-5% of diagnosed COVID-19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.
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Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model.
Mongioì, LM, Barbagallo, F, Condorelli, RA, Cannarella, R, Aversa, A, La Vignera, S, Calogero, AE
Endocrine. 2020;68(3):467-470
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Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Little is known about how it affects the endocrine system and it is likely that some patients who have recovered may suffer long-term consequences. The severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS outbreak in 2003 has many similarities. This editorial looks at the possible effects on the endocrine system of SARS-CoV-2 by looking at the long-term effects seen in SARS. In the case of SARS-CoV, it was thought that the virus could directly damage pancreatic cells leading to type 2 diabetes. It is hypothesized that Covid-19 patients could develop this condition by the same mechanism. Although no study on SARS reported the link between obesity and higher mortality rate, there is evidence that obese Covid-19 patients have worse clinical outcomes. There is no data yet for Covid-19, but adrenal insufficiency and impaired thyroid function were shown in some cases of SARS. To identify and treat any possible long-term effects of Covid-19, endocrinologists should monitor hormone levels and metabolic functions.
Abstract
The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is centralizing the interest of the scientific world. In the next months, long-term consequences on the endocrine system may arise following COVID-19. In this article, we hypothesized the effects of SARS-CoV-2 taking into account what learned from the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused SARS in 2003.
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Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery.
Rubino, F, Cohen, RV, Mingrone, G, le Roux, CW, Mechanick, JI, Arterburn, DE, Vidal, J, Alberti, G, Amiel, SA, Batterham, RL, et al
The lancet. Diabetes & endocrinology. 2020;8(7):640-648
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Bariatric surgery has been proven for weight loss in people with severe obesity. However, during the covid-19 pandemic, surgery has been postponed for many individuals. Under normal conditions, patients who are awaiting bariatric surgery are prioritised based on weight, however this does not necessarily reflect severity of their condition. This review paper aimed to develop new criteria in order to help prioritise individuals who are awaiting bariatric surgery. The authors began by reviewing the reasons for delaying bariatric surgery and the need for beds, the risks of covid-19 transmission during the procedure and the severe covid-19 complications that individuals with obesity can experience were discussed. A recommendation was made that all patients having bariatric surgery be tested for Covid-19. Solutions were proposed for those awaiting surgery such as diets, exercise, optimal blood sugar control and the potential use of weight loss medications. Prioritisation of surgery should focus on clinical need; it should be accessible and minimise harm from delays. Individuals with obesity and type 2 diabetes should be prioritised based on those who have an increased risk of death, determined by whether the individual; has poor blood sugar control despite maximal use of medications to control it, uses insulin, has previous heart disease, has liver disease or if they have other risk factors. It was concluded that weight alone is inadequate to prioritise candidates for bariatric surgery. Disease severity should be at the centre of decisions, especially when access to surgery is reduced, as is during the Covid -19 pandemic. This paper could be used by healthcare professionals to understand how to prioritise their obese and type 2 diabetic patients who are awaiting bariatric surgery.
Abstract
The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation.