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Metformin (MTF) is the only biguanide included in the World Health Organization's list of essential medicines; representing a widespread drug in the management of diabetes mellitus. With its accessibility and affordability being one of its biggest assets, it has become the target of interest for many trying to find alternative treatments for varied pathologies. Over time, an increasing body of evidence has shown additional roles of MTF, with unexpected interactions of benefit in other diseases. Metformin (MTF) holds significant promise in mitigating ischemia-reperfusion injury (IRI), particularly in the realm of organ transplantation. As acceptance criteria for organ transplants expand, IRI during the preservation phase remain a major concern within the transplant community, prompting a keen interest in MTF's effects. Emerging evidence suggests that administering MTF during reperfusion may activate the reperfusion injury salvage kinase (RISK) pathway. This pathway is pivotal in alleviating IRI in transplant recipients, potentially leading to improved outcomes such as reduced rates of organ rejection. This review aims to contextualize MTF historically, explore its current uses, pharmacokinetics, and pharmacodynamics, and link these aspects to the pathophysiology of IRI to illuminate its potential future role in transplantation. A comprehensive survey of the current literature highlights MTF's potential to recondition and protect against IRI by attenuating free radical damage, activating AMP-activated protein kinase to preserve cellular energy and promote repair, as well as directly reducing inflammation and enhancing microcirculation.
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Background: Cardiovascular and renal diseases represent a major determinant for the morbidity and mortality associated with obesity and type 2 diabetes mellitus (T2DM). Bariatric surgery is considered one of the few treatments with the potential to reverse cardiovascular, renal and metabolic disease. Methods: Prospective study of patients undergoing sleeve gastrectomy collecting pre- and post-surgery creatinine, eGFR, glucose, insulin, total, LDL/HDL cholesterol, triglycerides, parathyroid hormone, vitamin D3, C- Reactive Protein (CRP), blood count, weight, body mass index (BMI), bilateral carotid intima media thickness (IMT), flow-mediated dilation (FMD) and epicardial adipose tissue (EAT). Measurements were compared at 1 year follow up. Results: 24 patients were included in the study. Cardiovascular parameters, as HDL-cholesterol (p = 0.002), IMT (p = 0.003), EAT (p < 0.001) and FMD (p = 0.001) showed significant improvement after surgery. Secondary renal outcomes including Vitamin D3 (p < 0.0001), Calcium (p = 0.006), RBCs (p = 0.007), HCO3- (p = 0.05) also ameliorated as well as BMI (p < 0.001). Conclusions: Sleeve gastrectomy has a positive impact on cardiovascular, renal, and metabolic parameters in patients with morbid obesity, suggesting it may halt the progression of these diseases even in the preclinical stage. Further research is needed to explore the long-term effects underlying these improvements.
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INTRODUCTION: Global chronic kidney disease is now epidemic, with substantial health and economic consequences. While scientific support for living donor renal transplants (LDRT) is strong, donor shortages necessitate consideration of expanded criteria, including obese individuals. Bariatric surgery (BS) may mitigate obesity-related risks, but research on living donor candidates is scarce. Our scoping review aims to compile evidence, identify gaps, and formulate an algorithm to guide healthcare professionals in evaluating BS for obese living donors. EVIDENCE ACQUISITION: We did a systematic search of studies on living kidney donors and obesity. We searched the MEDLINE Ovid, Embase Ovid, CENTRAL and Web of Science databases for studies from database inception to March 30, 2023. All English-language articles available in full text have been considered. Excluded are commentaries, editorials, letters, and abstracts. EVIDENCE SYNTHESIS: Obesity in LDRT raises long-term ESRD risk. Current high BMI donor admission raises ethical and clinical concerns. Encouraging timely weight loss can make obese candidates suitable donors, reducing risks. Sleeve gastrectomy is the most reported and preferable approach, since it minimizes hyperoxaluria risk. Re-evaluation for donation is possible 6-12 months post-BS, with BMI<35 for three months. Cost-benefit analysis favors BS over nephrectomy in obese donors (cost-benefit ratio: 3.64) when graft survival is equal. CONCLUSIONS: BS shows promise with short-term effectiveness and potential long-term outcomes. However, it should not be perceived as a means to expand the donor pool but rather as a personalized approach to address obesity and improve individuals' health.
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Algoritmos , Cirurgia Bariátrica , Transplante de Rim , Doadores Vivos , Obesidade , Humanos , Obesidade/cirurgia , Nefrectomia , Falência Renal Crônica/cirurgiaRESUMO
Background: Temporary intravascular shunts (TIVS) may allow quick revascularization and distal reperfusion, reducing the ischemic time (IT) when an arterial injury occurs. Furthermore, TIVS temporarily restore peripheral perfusion during the treatment of concomitant life-threatening injuries or when patients require evacuation to a higher level of care. Notwithstanding, there are still disputes regarding the use of TIVS, in view of the paucity of evidence in terms of potential benefits and with regard to the anticoagulation during the procedure. The present study aimed to assess TIVS impact, safety, and timing on limb salvage in complex civilian vascular traumas. Patients and methods: Data were retrieved from the prospective database of our department, which included all patients hospitalized with a vascular injury of the extremities between January 2006 and December 2022. Patients undergoing TIVS during vascular injury management were included in group A, and those who could not postpone immediate care for TIVS insertion were included in group B (control group). Data concerning the times required for extremity revascularization or other surgical procedures such as orthopedic interventions and the time of limb ischemia were compared between the two groups. A comparison of the postoperative course between the two groups was also performed. Results: A total of 53 patients were included: group A (TIVS insertion, n = 31) and group B (control, n = 22). Revascularization time significantly differed (p = 0.002) between the two groups, which is lower in group A (4.17 ± 2.37â h vs. 5.81 ± 1.26â h). TIVS positively affected the probability of limb salvage (p = 0.02). At multivariate analysis, the factors independently associated with limb salvage were TIVS usage, the necessity of hyperbaric oxygen therapy, and the total IT. In group A, there were three deaths and one major amputation, and in group B, there were two deaths and four major amputations. Conclusions: The use of TIVS minimizes revascularization time and improves limb salvage probability. A multidisciplinary approach is recommended, and correct surgical timing is key to ensure the best outcome.
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Sleep is a vital process essential for survival. The trend of reduction in the time dedicated to sleep has increased in industrialized countries, together with the dramatic increase in the prevalence of obesity and diabetes. Short sleep may increase the risk of obesity, diabetes and cardiovascular disease, and on the other hand, obesity is associated with sleep disorders, such as obstructive apnea disease, insomnia and excessive daytime sleepiness. Sleep and metabolic disorders are linked; therefore, identifying the physiological and molecular pathways involved in sleep regulation and metabolic homeostasis can play a major role in ameliorating the metabolic health of the individual. Approaches aimed at reducing body weight could provide benefits for both cardiometabolic risk and sleep quality, which indirectly, in turn, may determine an amelioration of the cardiometabolic phenotype of individuals. We revised the literature on weight loss and sleep, focusing on the mechanisms and the molecules that may subtend this relationship in humans as in animal models.
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Doenças Cardiovasculares , Diabetes Mellitus , Animais , Humanos , Sono/fisiologia , Obesidade , Redução de Peso , Modelos Animais , Doenças Cardiovasculares/complicaçõesRESUMO
BACKGROUND: There is significant debate regarding the existence of sex-related differences in the presentation, treatment, and outcomes of men versus women affected by abdominal aortic aneurysm (AAA). The purpose of this study is to compare endovascular aneurysm repair (EVAR) of infrarenal AAAs with the current sex-neutral 5.0-5.5 cm-diameter threshold for intervention between the two sexes. METHODS: Retrospective review of consecutive cases from a single teaching institution over a period of five years of patients who had undergone elective EVAR for AAAs between 5.0 and 5.5 cm in diameter. Outcomes of interest were compared according to sex. RESULTS: Ninety-four patients were included in the analysis, with a higher prevalence of men (53%). Females were older at the time of repair, 78 ± 5.1 years, versus 71.7 ± 7 years (p < 0.01), and had higher incidence of underlying comorbidities, namely, arrhythmia, chronic kidney disease, and previous carotid revascularization. Women had higher incidence of immediate systemic complications (p = 0.021), post-operative AMI (p = 0.001), arrhythmia (p = 0.006), pulmonary oedema (p < 0.001), and persistent renal dysfunction (p = 0.029). Multivariate analysis for post-operative factors associated to mortality and adjusted for sex confirmed that AMI (p = 0.015), arrhythmia (p = 0.049), pulmonary oedema (p = 0.015), persistent renal dysfunction (p < 0.001), cerebral ischemia (p < 0.001), arterial embolism of lower limbs (p < 0.001), and deep-vein thrombosis of lower limbs (p < 0.001) were associated to higher EVAR-related mortality; a higher incidence of post-operative AMI (p = 0.014), pulmonary edema (p = 0.034), and arterial embolism of lower limbs (p = 0.046) were associated to higher 30-days mortality. In females there was also a higher rate of suprarenal fixation (p = 0.026), insertion outside the instruction for use (p = 0.035), and a more hostile neck anatomy with different proximal aortic diameter (p < 0.001) and angle (p = 0.003). CONCLUSIONS: A similar threshold of size of AAA for elective surgery for both males and females might not be appropriate for surgical intervention, as females tend to have worse outcomes. Further population-based studies are needed to guide on sex-related differences and intervention on AAA.
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Biliary lithiasis is a global disorder affecting nearly 20% of the world's population, although most cases occur without symptoms. Gallbladder stones could move into the common bile duct after gallbladder contraction, causing acute cholecystitis. The progression of the acute disease can take different forms, from mild inflammation, treatable with oral antibiotics, to the most severe forms with septic shock or biliary peritonitis, requiring specific treatment. Liver function tests and abdominal ultrasound are generally sufficient for diagnostic purposes. The most commonly used antibiotic is penicillin, with piperacillin achieving the best results; alternatively, fluoroquinolones could also be used, although there is no univocal consensus and surgery remains the only definitive treatment. A prolonged antibiotic therapy after cholecystectomy seems inadvisable, except in severe cases and/or in the immuno-compromised patient, where it should be periodically evaluated to avoid antibiotic resistance and unnecessary use. This review presents an evidence-based analysis to describe the advantages and disadvantages of the available options for the treatment of biliary lithiasis and cholecystitis, from the pathophysiological mechanisms behind lithiasis formation and also covering the main diagnostic findings for biliary stones, recommending an approach tailored to the patient's characteristics and to the team's expertise.
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Background: There is controversy regarding the suitability of high body mass index (BMI) candidates accessing the transplant waitlist. Patients and methods: Observational study on consecutive kidney transplant recipients undergoing surgery between January 2014 and March 2016 at our center. Patients were stratified according to BMI. Survival outcomes and graft function were analyzed to investigate the effect of donor's and recipient's demographic characteristics. Results: 396 kidney transplant recipients: 260 males, mean age 51.8 ± 15.9 years, followed up for a mean time of 5.86 ± 2.29 years. Mean BMI 26.2 ± 5.1. BMI class 1 (20 ≤ BMI ≤ 24.9) n=133, class 2 (25 ≤ BMI ≤ 29.9) n= 155, class 3 (30 ≤ BMI ≤34.9) n=53, class 4 (BMI ≥ 35) n=21, class V (BMI ≤ 19.9) n=34. Patient survival was not significantly different according to the recipient's BMI class (p=0.476); graft survival was affected (p=0.031), as well as graft function up to 2 years post-transplant and at 4 years follow up (p=0.016). At logistic regression the factors independently associated with graft loss were only donor's age (p=0.05) and BMI class of the recipient (p=0.002). Conclusions: Obesity did not impact on patient's survival but affected graft function and graft loss.
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Transplante de Rim , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Massa Corporal , Estudos de Coortes , Sobrevivência de Enxerto , ObesidadeRESUMO
BACKGROUND: Acute appendicitis (AA) is one of the main indications for urgent surgery. Laparoscopic appendectomy (LA) has shown advantages in terms of clinical results and cost-effectiveness, even if there is still controversy about different devices to utilize, especially with regards to the endoloop (EL) vs endostapler (ES) when it comes to stump closure. AIM: To compare safety and cost-effectiveness of EL vs ES. METHODS: From a prospectively maintained database, data of 996 consecutive patients treated by LA with a 3 years-follow up in the department of Emergency General Surgery - St Orsola University Hospital, Bologna (Italy) were retrieved. A meta-analysis was performed in terms of surgical complications, in comparison to the international literature published from 1995 to 2021. RESULTS: The meta-analysis showed no evidence regarding wound infections, abdominal abscesses, and total post-operative complications, in terms of superiority of a surgical technique for the stump closure in LA. CONCLUSION: Even when AA is complicated, the routine use of EL is safe in most patients.
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Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in the world and represents a clinical-histopathologic entity where the steatosis component may vary in degree and may or may not have fibrotic progression. The key concept of NAFLD pathogenesis is excessive triglyceride hepatic accumulation because of an imbalance between free fatty acid influx and efflux. Strong epidemiological, biochemical, and therapeutic evidence supports the premise that the primary pathophysiological derangement in most patients with NAFLD is insulin resistance; thus the association between diabetes and NAFLD is widely recognized in the literature. Since NAFLD is the hepatic manifestation of a metabolic disease, it is also associated with a higher cardio-vascular risk. Conventional B-mode ultrasound is widely adopted as a first-line imaging modality for hepatic steatosis, although magnetic resonance imaging represents the gold standard noninvasive modality for quantifying the amount of fat in these patients. Treatment of NAFLD patients depends on the disease severity, ranging from a more benign condition of nonalcoholic fatty liver to nonalcoholic steatohepatitis. Abstinence from alcohol, a Mediterranean diet, and modification of risk factors are recommended for patients suffering from NAFLD to avoid major cardiovascular events, as per all diabetic patients. In addition, weight loss induced by bariatric surgery seems to also be effective in improving liver features, together with the benefits for diabetes control or resolution, dyslipidemia, and hypertension. Finally, liver transplantation represents the ultimate treatment for severe nonalcoholic fatty liver disease and is growing rapidly as a main indication in Western countries. This review offers a comprehensive multidisciplinary approach to NAFLD, highlighting its connection with diabetes.
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There is a deep interrelation between the thyroid gland and the kidney parenchyma, with dysfunction of the first leading to significant changes in renal metabolism and vice versa. Given the recognition of cancer as a systemic disease, the raise of thyroid tumors and the common association of several malignancies, such as breast cancer, prostate cancer, colorectal cancer, and other, with an increased risk of kidney disease, public health alert for these conditions is warranted. A systematic review of the current evidence on the bidirectional relationship between thyroid and renal cancers was conducted including 18 studies, highlighting patient's characteristics, histology, time for secondary malignancy to develop from the first diagnosis, treatment, and follow-up. A total of 776 patients were identified; median age was 64 years (range: 7-76 years). Obesity and family history were identified as the most common risk factors, and genetic susceptibility was suggested with a potential strong association with Cowden syndrome. Controversy on chemo and radiotherapy effects was found, as not all patients were previously exposed to these treatments. Men were more likely to develop kidney cancer after a primary thyroid malignancy, with 423/776 (54%) experiencing renal disease secondarily. Median time after the first malignancy was 5.2 years (range: 0-20 years). With the advancement of current oncological therapy, the prognosis for thyroid cancer patients has improved, although there has been a corresponding rise in the incidence of multiple secondary malignancy within the same population, particularly concerning the kidney. Surgery can achieve disease-free survival, if surveillance follow-up allows for an early localized form, where radical treatment is recommended.
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Cancer cells are characterized by the reprogramming of certain cell metabolisms via activation of definite pathways and regulation of gene signaling. Ischemia-reperfusion injury (IRI) is characterized by tissue damage and death following a lack of perfusion and oxygenation. It is most commonly seen in the setting of organ transplantation. Interestingly, the microenvironments seen in cancer and ischemic tissues are quite similar, especially due to the hypoxic state that occurs in both. As a consequence, there is genetic signaling involved in response to IRI that has common pathways with cancer. Some of these changes are seen across the board with many cancer cells and are known as Hallmarks of Cancer, among which are aerobic glycolysis and the induction of angiogenesis. This literature review aims to compare the metabolic pathways that are altered in cancer tissues and in normal tissues subjected to IRI in order to find common adaptive processes and to identify key pathways that could represent a therapeutic target in both pathologies. By increasing our understanding of this relationship, clinical correlations can be made and applied practically to improve outcomes of transplanted organs, given the known association with acute rejection, delayed graft function, and poor graft survival. The following metabolic pathways are discussed in our review, both in the setting of cancer and IRI: apoptosis, glycolysis, and angiogenesis. The role of the immune system in both pathologies as well as mitochondrial function and the production of reactive oxygen species (ROS) are reviewed.
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Machine learning (ML) is an interdisciplinary sector in the subset of artificial intelligence (AI) that creates systems to set up logical connections using algorithms, and thus offers predictions for complex data analysis. In the present review, an up-to-date summary of the current state of the art regarding ML and AI implementation for thyroid nodule ultrasound characterization and cancer is provided, highlighting controversies over AI application as well as possible benefits of ML, such as, for example, training purposes. There is evidence that AI increases diagnostic accuracy and significantly limits inter-observer variability by using standardized mathematical algorithms. It could also be of aid in practice settings with limited sub-specialty expertise, offering a second opinion by means of radiomics and computer-assisted diagnosis. The introduction of AI represents a revolutionary event in thyroid nodule evaluation, but key issues for further implementation include integration with radiologist expertise, impact on workflow and efficiency, and performance monitoring.
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Differentiated thyroid cancers (DTCs) are slow-growing malignant tumours, including papillary and follicular carcinomas. Overall, prognosis is good, although it tends to worsen when local invasion occurs with bulky cervical nodes, or in the case of distant metastases. Surgery represents the main treatment for DTCs. However, radical excision is challenging and significant morbidity and functional loss can follow the treatment of the more advanced forms. Literature on advanced thyroid tumours, both differentiated and undifferentiated, does not provide clear and specific guidelines. This emerges the need for a tailored and multidisciplinary approach. In the present study, we report our single-centre experience of 111 advanced (local, regional, and distant) DTCs, investigating the rate of radical excision, peri-procedural and post-procedural complications, quality of life, persistence, recurrence rates, and survival rates. Results are critically appraised and compared to the existing published evidence review.
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Renal transplantation (RT) is the treatment of choice for end-stage renal disease, significantly improving patients' survival and quality of life. However, approximately 3-23% of patients encounter post-operative complications, and radiology plays a major role for their early detection and treatment or follow-up planning. CT and MRI are excellent imaging modalities to evaluate renal transplant post-operative course; nevertheless, they are both associated with a high cost and low accessibility, as well as some contraindications, making them not feasible for all patients. In particular, gadolinium-based contrast can lead to the rare condition of nephrogenic systemic fibrosis, and iodine-based contrast can lead to contrast-induced nephropathy (CIN). CT also exposes the patients who may require multiple examinations to ionizing radiation. Therefore, considering the overall advantages and disadvantages, contrast-enhanced ultrasound (CEUS) is presently considered an effective first-line imaging modality for post-operative early and long-term follow-up in RT, reducing the need for biopsies and providing adequate guidance for drainage procedures. Hence, this paper aims to review the updated knowledge on CEUS compared with CT and MRI for the evaluation of RT renal transplant complications; advantages, limitations, and possible recommendations are provided.
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Nefropatias , Transplante de Rim , Meios de Contraste/efeitos adversos , Humanos , Transplante de Rim/efeitos adversos , Imageamento por Ressonância Magnética/métodos , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Tomografia Computadorizada por Raios X/métodosRESUMO
BACKGROUND: Literature regarding ergonomic protocols for surgery is lacking, and there is a paucity of information on how this impacts on gender differences with regards to the barriers faced by women in surgery. METHODS: This article reviews current literature addressing women in surgery and ergonomics through a systematic search including the Web of Science, Scopus, and PubMed databases. RESULTS: Searches retrieved 425 items, and after a thorough evaluation for inclusion, 15 studies were examined-predominantly surveys (n = 9) and originating from the USA (n = 9). Identified ergonomic challenges included the general shorter height and smaller glove size of women. Furthermore, women experienced more musculoskeletal pain than men, potentially because the size and design of theatre tools are designed for male and tall individuals, highlighting an unconscious gender bias still pervading the surgical field. CONCLUSIONS: As more women enter medicine and pursue surgical careers, it is essential to foster a culture of diversity and inclusion in theatre to develop more ergonomic environments.