Gestational Diabetes Risk and Low Birth Weight After Metabolic Bariatric Surgery: a Complex Interplay to be Balanced.

INTRODUCTION: Metabolic bariatric surgery (MBS) is known to improve the obstetric outcomes of women with obesity and to prevent gestational diabetes (GD). To what extent does MBS decreases GD, without incurring at additional risks is a matter of concern. METHODS: A retrospective case-control study to compare the pregnancy outcomes of women previously submitted to MBS to those of age and preconception body mass index (PC BMI) matched non-operated controls. RESULTS: Pregnancies of women after MBS (n = 79) and matched controls (n = 79) were included. GD was significantly less frequent after MBS (7.6% vs. 19%; p = 0.03). Fasting blood glucose (76.90 ± 0.77 vs 80.37 ± 1.15 mg/dl, p < 0.05; 70.08 ± 1.34 vs. 76.35 ± 0.95 mg/dl; p < 0.05, first and second trimesters respectively) and birth weight (2953.67 ± 489.51 g vs. 3229.11 ± 476.21 g; p < 0.01) were significantly lower after MBS when compared to controls. The occurrence of small-for-gestational-age (SGA) was more frequent after MBS (22.8% vs. 6.3%; p < 0.01), but no longer significant after controlling for smoking habits (15.5% vs. 6%, p = 0.14). There were no significant differences in gestational weight gain, prematurity rate nor mode of delivery between groups. CONCLUSION: MBS was associated with a lower prevalence of GD than observed in non-operated women with the same age and BMI. After controlling for smoking, this occurred at the expense of a lower birth weight. Our data reinforces the hypothesis that MBS has body weight independent effects on glucose kinetics during pregnancy with distinctive impacts for mother and offspring, which need to be balanced.

Epidural Hematoma in Minor Hepatic Metastasectomy.

Liver resection poses many challenges for the anesthesiologist, including intraoperative hemodynamic instability, postoperative pain, and risk of coagulopathy. We report a case of epidural hematoma after epidural catheter removal, following a minor liver single metastasectomy. The main purpose of this case report is to bring to light the false security provided by traditional coagulation parameters and whether further investigation should be considered in selected cases, before handling neuraxial catheters. Alterations in coagulation after a partial hepatectomy remain poorly understood; thus, we believe that additional hemostatic values such as viscoelastic testing might be considered to better assess these patients.

Beyond restrictive: Sleeve Gastrectomy to Single Anastomosis Duodenoileal Bypass with Sleeve Gastrectomy as a spectrum of one single procedure.

INTRODUCTION: Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S) is a restrictive/hypoabsorptive procedure recommended for patients with obesity class 3. For safety reasons, SADI-S can be splited into a two-step procedure by performing a sleeve gastrectomy (SG) first. This stepwise approach also provides an unprecedented opportunity to disentangle the weight loss mechanisms triggered by each component. The objective was to compare weight trajectories and postprandial endocrine and metabolic responses of patients with obesity class 3 submitted to SADI-S or sleeve gastrectomy (SG) as the first step of SADI-S. METHODS: Subjects submitted to SADI-S (n=7) or SG (n=7) at a tertiary referral public academic hospital, underwent anthropometric evaluation and a liquid mixed meal tolerance test (MMTT) pre-operatively and at 3, 6, and 12 months post-operatively. RESULTS: Anthropometric parameters, as well as metabolic and micronutrient profiles, were not significantly different between groups, neither before nor after surgery. There were no significant differences in fasting or post-prandial glucose, insulin, C-peptide, ghrelin, insulin secretion rate (ISR) and insulin clearance during the MMTT between subjects submitted to SADI-S and SG. There was no lost to follow-up. CONCLUSIONS: The restrictive component seems to be the main driver for weight loss and metabolic adaptations observed during the first 12 months after SADI-S, given that the weight trajectories and metabolic profiles do not differ from SG. This data provides support for a surgeons' choice of a two-step SADI-S without jeopardizing the weight loss outcomes.

Enhancing Native Plant Establishment in Mine Tailings under Drought Stress Conditions through the Application of Organo-Mineral Amendments and Microbial Inoculants.

The implementation of phytoremediation strategies under arid and semiarid climates requires the use of appropriate plant species capable of withstanding multiple abiotic stresses. In this study, we assessed the combined effects of organo-mineral amendments and microbial inoculants on the chemical and biological properties of mine tailings, as well as on the growth of native plant species under drought stress conditions. Plants were cultivated in pots containing 1 kg of a mixture of mine tailings and topsoil (i.e., pre-mined superficial soil) in a 60:40 ratio, 6% marble sludge, and 10% sheep manure. Moreover, a consortium of four drought-resistant plant growth-promoting rhizobacteria (PGPR) was inoculated. Three irrigation levels were applied: well-watered, moderate water deficit, and severe water deficit, corresponding to 80%, 45%, and 30% of field capacity, respectively. The addition of topsoil and organo-mineral amendments to mine tailings significantly improved their chemical and biological properties, which were further enhanced by bacterial inoculation and plants' establishment. Water stress negatively impacted enzymatic activities in amended tailings, resulting in a significant decrease in acid and alkaline phosphatases, urease, and dehydrogenase activities. Similar results were obtained for bacteria, fungi, and actinomycete abundance. PGPR inoculation positively influenced the availability of phosphorus, total nitrogen, and organic carbon, while it increased alkaline phosphatase, urease (by about 10%), and dehydrogenase activity (by 50%). The rhizosphere of Peganum harmala showed the highest enzymatic activity and number of culturable microorganisms, especially in inoculated treatments. Severe water deficit negatively affected plant growth, leading to a 40% reduction in the shoot biomass of both Atriplex halimus and Pennisetum setaceum compared to well-watered plants. P. harmala showed greater tolerance to water stress, evidenced by lower decreases observed in root and shoot length and dry weight compared to well-watered plants. The use of bioinoculants mitigated the negative effects of drought on P. harmala shoot biomass, resulting in an increase of up to 75% in the aerial biomass in plants exposed to severe water deficit. In conclusion, the results suggest that the combination of organo-mineral amendments, PGPR inoculation, and P. harmala represents a promising approach to enhance the phytoremediation of metal-polluted soils under semiarid conditions.

Lymphoplasmocytic plaque in children: A report of an atypical location.

Lymphoplasmocytic plaque in children (LPC) is a rare and distinctive skin disorder primarily affecting the pediatric population. Characterized by its unique histopathological features, the condition manifests as well-defined plaques with a predominance of lymphocytes and plasma cells infiltrating the dermis. Despite its limited prevalence, recognizing this entity is crucial for accurate diagnosis and appropriate management of affected patients. We report the case of a 10-year-old male presenting with LPC in the extensor surface of the upper arm, a rarely reported location, treated with both topical and intralesional corticosteroids resulting in partial improvement.

Automated image label extraction from radiology reports - A review.

Machine Learning models need large amounts of annotated data for training. In the field of medical imaging, labeled data is especially difficult to obtain because the annotations have to be performed by qualified physicians. Natural Language Processing (NLP) tools can be applied to radiology reports to extract labels for medical images automatically. Compared to manual labeling, this approach requires smaller annotation efforts and can therefore facilitate the creation of labeled medical image data sets. In this article, we summarize the literature on this topic spanning from 2013 to 2023, starting with a meta-analysis of the included articles, followed by a qualitative and quantitative systematization of the results. Overall, we found four types of studies on the extraction of labels from radiology reports: those describing systems based on symbolic NLP, statistical NLP, neural NLP, and those describing systems combining or comparing two or more of the latter. Despite the large variety of existing approaches, there is still room for further improvement. This work can contribute to the development of new techniques or the improvement of existing ones.

Giant Tophaceous Gout: The Importance of Therapeutic Compliance.

Gout is a metabolic disease resulting from the deposition of monosodium urate crystals in joints, tissues, and organs. Nowadays, the treatment of hyperuricemia is easily accessible and widespread and mainly consists of xanthine oxidase inhibitors and uricosurics. In refractory and advanced cases of gout, amputation surgery may be required. The authors present the case of an 85-year-old man who is non-compliant with hypouricemic medication, has exuberant gout, and has refused amputation surgery several times. The patient went to the emergency department with a triad of acute kidney injuries, acute gout, and poorly controlled pain. Cases of tophaceus gout such as the one presented are very rare nowadays.

Have immigrant children been left behind in COVID-19 testing rates? - A quantitative study in the Lisbon metropolitan area between march 2020 and may 2023.

Immigrant children often encounter additional barriers in accessing health care than their peers. However, there is a lack of evidence globally regarding how migrant status may have affected access to COVID-19 testing during the pandemic. This study aimed to analyze migrant status as a determinant of COVID-19 testing rates among children in the Lisbon metropolitan area, Portugal. This cross-sequential study included 722 children aged 2-8 years (47% non-immigrants; 53% immigrants). We collected data from a national surveillance system on laboratory-confirmed COVID-19 tests conducted between March 2020 and May 2023 and assessed whether children were ever tested for COVID-19 and testing frequency. We employed robust and standard Poisson regression models to estimate Adjusted Prevalence Ratios and Relative Risks with 95% confidence intervals. A total of 637 tests were performed. Immigrant children had lower testing rates (53% vs. 48%) and fewer tests per child (median: 2 vs. 3). Moreover, they were 17% less likely to be ever tested (PR = 0.83, 95% CI: 0.76-0.89) and performed 26% fewer tests (RR = 0.74, 95% CI: 0.67-0.82) compared to non-immigrant children. Caregiver's age, education, employment status, child's birth weight, and perceived health status were associated factors. Our findings suggest that the COVID-19 pandemic has left immigrant children somewhat behind. We conclude that specific interventions targeting vulnerable populations, such as immigrant children, are needed in future health crises.

STERN: Attention-driven Spatial Transformer Network for abnormality detection in chest X-ray images.

Chest X-ray scans are frequently requested to detect the presence of abnormalities, due to their low-cost and non-invasive nature. The interpretation of these images can be automated to prioritize more urgent exams through deep learning models, but the presence of image artifacts, e.g. lettering, often generates a harmful bias in the classifiers and an increase of false positive results. Consequently, healthcare would benefit from a system that selects the thoracic region of interest prior to deciding whether an image is possibly pathologic. The current work tackles this binary classification exercise, in which an image is either normal or abnormal, using an attention-driven and spatially unsupervised Spatial Transformer Network (STERN), that takes advantage of a novel domain-specific loss to better frame the region of interest. Unlike the state of the art, in which this type of networks is usually employed for image alignment, this work proposes a spatial transformer module that is used specifically for attention, as an alternative to the standard object detection models that typically precede the classifier to crop out the region of interest. In sum, the proposed end-to-end architecture dynamically scales and aligns the input images to maximize the classifier's performance, by selecting the thorax with translation and non-isotropic scaling transformations, and thus eliminating artifacts. Additionally, this paper provides an extensive and objective analysis of the selected regions of interest, by proposing a set of mathematical evaluation metrics. The results indicate that the STERN achieves similar results to using YOLO-cropped images, with reduced computational cost and without the need for localization labels. More specifically, the system is able to distinguish abnormal frontal images from the CheXpert dataset, with a mean AUC of 85.67% - a 2.55% improvement vs. the 0.98% improvement achieved by the YOLO-based counterpart in comparison to a standard baseline classifier. At the same time, the STERN approach requires less than 2/3 of the training parameters, while increasing the inference time per batch in less than 2 ms. Code available via GitHub.

Klotho and lean mass as novel cardiovascular risk factors in hemodialysis patients.

Background: Patients with chronic kidney disease (CKD) present a higher risk of cardiovascular (CV) morbidity and mortality compared with the general population. While there are several well-established traditional CV risk factors, few studies have addressed novel potential risk factors such as α-Klotho, asymmetric dimethylarginine (ADMA) and lean mass. Methods: This was an observational, prospective, single-center, cohort study that included prevalent hemodialysis (online hemodiafiltration) adult patients. By univariate logistic regression models, univariate and multivariate Cox proportional hazards models, and Kaplan-Meier analysis, we evaluated the association between the levels of α-Klotho, ADMA and lean mass, with the risk of peripheral vascular disease (PVD), CV events and all-cause mortality in these patients. Results: A total of 200 HD patients was included. We found that increased levels of log-α-Klotho were significantly associated with decreased odds of both PVD [odds ratio (OR) 0.521, 95% confidence interval (CI) 0.270-0.954, P = .034] and CV events (OR 0.415, 95% CI 0.203-0.790, P = .01), whereas increased levels of log-ADMA were only significantly associated with increased odds of PVD (OR 13.482, 95% CI 5.055-41.606, P < .001). We also found that the levels of log-α-Klotho (HR 0.357, 95% CI 0.140-0.906, P < .05) and lean mass (HR 0.187, 95% CI 0.042-0.829, P < .05), but not log-ADMA, were significantly associated with the risk of all-cause mortality, even after adjusting for possible confounding variables. Conclusions: Novel long-term clinical associations were generated that support α-Klotho and lean mass as novel CV risk factors in hemodialysis patients.

Chronic Intermittent Hypoxia-Induced Dysmetabolism Is Associated with Hepatic Oxidative Stress, Mitochondrial Dysfunction and Inflammation.

The association between obstructive sleep apnea (OSA) and metabolic disorders is well-established; however, the underlying mechanisms that elucidate this relationship remain incompletely understood. Since the liver is a major organ in the maintenance of metabolic homeostasis, we hypothesize that liver dysfunction plays a crucial role in the pathogenesis of metabolic dysfunction associated with obstructive sleep apnea (OSA). Herein, we explored the underlying mechanisms of this association within the liver. Experiments were performed in male Wistar rats fed with a control or high fat (HF) diet (60% lipid-rich) for 12 weeks. Half of the groups were exposed to chronic intermittent hypoxia (CIH) (30 hypoxic (5% O2) cycles, 8 h/day) that mimics OSA, in the last 15 days. Insulin sensitivity and glucose tolerance were assessed. Liver samples were collected for evaluation of lipid deposition, insulin signaling, glucose homeostasis, hypoxia, oxidative stress, antioxidant defenses, mitochondrial biogenesis and inflammation. Both the CIH and HF diet induced dysmetabolism, a state not aggravated in animals submitted to HF plus CIH. CIH aggravates hepatic lipid deposition in obese animals. Hypoxia-inducible factors levels were altered by these stimuli. CIH decreased the levels of oxidative phosphorylation complexes in both groups and the levels of SOD-1. The HF diet reduced mitochondrial density and hepatic antioxidant capacity. The CIH and HF diet produced alterations in cysteine-related thiols and pro-inflammatory markers. The results obtained suggest that hepatic mitochondrial dysfunction and oxidative stress, leading to inflammation, may be significant factors contributing to the development of dysmetabolism associated with OSA.

Parry Romberg Syndrome: When the Diagnosis of a Rare Disease Is Made in the Primary Care Setting.

Parry Romberg syndrome (PRS) is an acquired neurocutaneous syndrome with uncertain pathophysiology, and its incidence is unknown. Usually, the disease becomes apparent during the first decade of life or early during the second decade, but it can also occur in adulthood, and it is more common in females. The main feature is slowly progressive hemiatrophy (thinning or shrinkage) of the facial tissues, typically fat, skin, connective tissues, muscle, and sometimes bone. In some people, atrophy may also affect the trunk and the limbs. Additional symptoms can potentially develop in some patients, including ophthalmological, psychiatric, and neurological complications. The clinical presentation serves as a guide for the diagnosis. Treatment can demand a multidisciplinary approach (maxillofacial surgeons, plastic surgeons, ophthalmologists, neurologists, dermatologists, psychiatrists, anesthetists, and family doctors). Patients can undergo restorative plastic surgery to improve their appearance, with highly variable success rates. We present a case report of a 52-year-old man who made an appointment at the family care unit (FCU) because of a left facial hemiatrophy that started progressing two to three months before, and he was afraid it might be cancer. At the physical exam, it was possible to examine a slight hemiatrophy in two different parts of the left side of the patient's face (the nasolabial-masseter region and the temporal-malar region). The facial CT scan showed a low degree of maxillary bone resorption. Through discussion with peers on the Family Doctor team, the diagnosis of a rare condition in the primary care setting was made possible. This case shows the importance of being aware of a rare disease despite working as a family physician and aims to make more people familiar with this syndrome. It also raises awareness about the need for discussion of clinical cases as a team.

Bedside ultrasound in post-anaesthetic care unit for the diagnosis of post-extubation negative pressure pulmonary oedema: A paediatric case.

BACKGROUND: Post-extubation negative pressure pulmonary oedema is a rare, potentially life-threatening complication associated with general anaesthesia. Chest radiography is used as a diagnostic tool, but it implies a non-negligible radiation exposure, a very important consideration, especially for the paediatric population. However, lung ultrasound can overcome this problem and can be used to detect postoperative pulmonary complications. CASE REPORT: A 16-year-old male was scheduled for tympanoplasty. General anaesthesia was conducted, and after extubation, the patient developed a laryngospasm. On arrival at the post-anaesthetic care unit, the patient started to cough, a pink frothy sputum and hypoxemia were noticed, and auscultation revealed crepitations. A bedside lung ultrasound showed more than three B-lines per intercostal window, suggesting an alveolar-interstitial syndrome. DISCUSSION: With this case report, we would like to raise awareness to this clinical entity and demonstrate bedside ultrasound has an important role in the diagnostic and therapeutic assessment during the perioperative period.

Mesothelial Cells Exhibit Characteristics of Perivascular Cells in an In Vitro Angiogenesis Assay.

Mesothelial cells have been shown to have remarkable plasticity towards mesenchymal cell types during development and in disease situations. Here, we have characterized the potential of mesothelial cells to undergo changes toward perivascular cells using an in vitro angiogenesis assay. We demonstrate that GFP-labeled mesothelial cells (GFP-MCs) aligned closely and specifically with endothelial networks formed when human dermal microvascular endothelial cells (HDMECs) were cultured in the presence of VEGF-A165 on normal human dermal fibroblasts (NHDFs) for a 7-day period. The co-culture with GFP-MCs had a positive effect on branch point formation indicating that the cells supported endothelial tube formation. We interrogated the molecular response of the GFP-MCs to the angiogenic co-culture by qRT-PCR and found that the pericyte marker Ng2 was upregulated when the cells were co-cultured with HDMECs on NHDFs, indicating a change towards a perivascular phenotype. When GFP-MCs were cultured on the NHDF feeder layer, they upregulated the epithelial-mesenchymal transition marker Zeb1 and lost their circularity while increasing their size, indicating a change to a more migratory cell type. We analyzed the pericyte-like behavior of the GFP-MCs in a 3D cardiac microtissue (spheroid) with cardiomyocytes, cardiac fibroblasts and cardiac endothelial cells where the mesothelial cells showed alignment with the endothelial cells. These results indicate that mesothelial cells have the potential to adopt a perivascular phenotype and associate with endothelial cells to potentially support angiogenesis.

Chronic intermittent hypoxia-induced cardiovascular and renal dysfunction: from adaptation to maladaptation.

Chronic intermittent hypoxia (CIH) is the dominant pathological feature of human obstructive sleep apnoea (OSA), which is highly prevalent and associated with cardiovascular and renal diseases. CIH causes hypertension, centred on sympathetic nervous overactivity, which persists following removal of the CIH stimulus. Molecular mechanisms contributing to CIH-induced hypertension have been carefully delineated. However, there is a dearth of knowledge on the efficacy of interventions to ameliorate high blood pressure in established disease. CIH causes endothelial dysfunction, aberrant structural remodelling of vessels and accelerates atherosclerotic processes. Pro-inflammatory and pro-oxidant pathways converge on disrupted nitric oxide signalling driving vascular dysfunction. In addition, CIH has adverse effects on the myocardium, manifesting atrial fibrillation, and cardiac remodelling progressing to contractile dysfunction. Sympatho-vagal imbalance, oxidative stress, inflammation, dysregulated HIF-1α transcriptional responses and resultant pro-apoptotic ER stress, calcium dysregulation, and mitochondrial dysfunction conspire to drive myocardial injury and failure. CIH elaborates direct and indirect effects in the kidney that initially contribute to the development of hypertension and later to chronic kidney disease. CIH-induced morphological damage of the kidney is dependent on TLR4/NF-κB/NLRP3/caspase-1 inflammasome activation and associated pyroptosis. Emerging potential therapies related to the gut-kidney axis and blockade of aryl hydrocarbon receptors (AhR) are promising. Cardiorenal outcomes in response to intermittent hypoxia present along a continuum from adaptation to maladaptation and are dependent on the intensity and duration of exposure to intermittent hypoxia. This heterogeneity of OSA is relevant to therapeutic treatment options and we argue the need for better stratification of OSA phenotypes.

Assessment of the Implementation of the International Health Regulations during the COVID-19 Pandemic: Portugal as a Case Study.

INTRODUCTION: The International Health Regulations (IHR) were developed to prepare countries to deal with public health emergencies. The spread of SARS-CoV-2 underlined the need for international coordination, although few attempts were made to evaluate the integrated implementation of the IHR's core capacities in response to the COVID-19 pandemic. The aim of this study was to evaluate whether IHR shortcomings stem from non-compliance or regulatory issues, using Portugal as a European case study due to its size, organization, and previous discrepancies between self-reporting and peer assessment of the IHR's core capacities. METHODS: Fifteen public health medical residents involved in contact tracing in mainland Portugal interpreted the effectiveness of the IHR's core capabilities by reviewing the publicly available evidence and reflecting on their own field experience, then grading each core capability according to the IHR Monitoring Framework. The assessment of IHR enforcement considered efforts made before and after the onset of the pandemic, covering the period up to July 2021. RESULTS: Four out of nine core IHR capacities (surveillance; response; risk communication; and human resource capacity) were classified as level 1, the lowest. Only two were graded level 3 (preparedness; and laboratory), the highest. The remaining three) (national legislation, policy & financing; coordination and national focal point communication; and points of entry) were classified as level 2. CONCLUSION: Portugal exemplifies the extent to which implementation of the IHR was not fully achieved, which has resulted in the underperformance of several core capacities. There is a need to improve preparedness and international cooperation in order to harmonize and strengthen the global response to public health emergencies, with better political, institutional, and financial support.

The Impact of Early-Stage Chronic Kidney Disease on Weight Loss Outcomes After Gastric Bypass.

PURPOSE: Weight loss achieved through bariatric metabolic surgery was demonstrated to be effective at reversing chronic kidney dysfunction associated with obesity-related glomerulopathy. However, robust data on how pre-operative kidney status impacts on bariatric metabolic surgery weight loss outcomes is still lacking. The aim of this study was to evaluate the impact of kidney dysfunction on weight loss outcomes after bariatric metabolic surgery. METHODS: Patients with obesity to be submitted to gastric bypass surgery underwent a pre-operative evaluation of creatinine clearance, estimated glomerular filtration rate (eGFR), proteinuria, and albuminuria in 24-hour urine. Body mass index (BMI), % total weight loss (%TWL), and % excess BMI loss (%EBMIL) were assessed at 6 and 12 months after surgery. RESULTS: Before surgery, patients (N=127) had a mean BMI of 39.6 ± 3.0 kg/m2, and 56.7% (n=72) had a creatinine clearance > 130 mL/min, 23.6% (n= 30) presented proteinuria > 150 mg/24h, and 15.0% (n= 19) presented albuminuria > 30 mg/24h. After surgery, the mean BMI was 27.7 kg/m2 and 25.0 kg/m2 at 6 and 12 months, respectively (p<0.0001). The %TWL was lower in patients with pre-operative eGFR < percentile 25 (34.4 ± 5.8% vs 39.4 ± 4.9%, p=0.0007, at 12 months). There were no significant correlations between weight loss metrics and pre-operative creatinine clearance rate, proteinuria, or albuminuria. CONCLUSION: Early-stage chronic kidney disease (G2) has a negative impact on short-term weight loss outcomes after bariatric metabolic surgery, albeit in a magnitude inferior to the clinically relevant threshold.

Impact of a heart failure multidisciplinary clinic on the reduction of healthcare-related events and costs: the GEstIC study.

Introduction: Heart failure (HF) is the leading cause of hospitalization in the elderly in developed countries and significantly impacts public health expenditures. Patients with HF usually have associated comorbidities that require multidisciplinary management. This study aims to demonstrate the benefits of a multidisciplinary clinic in reducing all-cause hospitalizations and HF events (HF hospitalizations and urgent HF visits) in a real-world setting. Finally, the study evaluates the associated costs of HF events. Methods: This observational study included patients admitted to GEstIC, a multidisciplinary Portuguese HF clinic, from January 2013 to February 2019, who had one-year follow-up. Hospitalizations and HF events, total days spent in the hospital during HF hospitalizations, and HF events-related costs, in the year before and the year after GEstIC admission, were compared. Results: Of the 487 patients admitted to the GEstIC, 287 were eligible for the study sample. After one year of HF patients' multidisciplinary management at GEstIC, there was a 53.7% reduction in all-cause hospitalizations (462 vs. 214), a 71.7% reduction in HF hospitalizations (392 vs. 111), and a 39.1% reduction in urgent HF visits (87 vs. 53). As a result, there was a significant decrease of 12.6 days in the length of hospital stay due to HF per patient (15.6 vs. 3.0, p < 0.001). This translated into the release of 9.9 hospital beds in the year following admission to GEstIC. The average total savings associated with the reduction of HF events was €5,439.77 per patient (6,774.15 vs. 1,334.38, p < 0.001), representing a total cost reduction of €1,561,213. Furthermore, the significant reduction in the number of all events was independent of the patient's left ventricular ejection fraction (LVEF). Discussion: Significant reductions in all-cause and HF hospitalizations and urgent HF visits were observed with the implementation of this multidisciplinary clinic for HF patients' management. This was particularly important for patients with LVEF >40%. Before GEstIC, there was no medical intervention to improve the prognosis of these patients. The reduction of over one million euros in health-related costs after only one year of person-centered multidisciplinary management highlights the need to replicate this approach in other national healthcare institutions.

A Clinically Relevant Dosage of Mitoxantrone Disrupts the Glutathione and Lipid Metabolic Pathways of the CD-1 Mice Brain: A Metabolomics Study.

Long-term cognitive dysfunction, or "chemobrain", has been observed in cancer patients treated with chemotherapy. Mitoxantrone (MTX) is a topoisomerase II inhibitor that binds and intercalates with DNA, being used in the treatment of several cancers and multiple sclerosis. Although MTX can induce chemobrain, its neurotoxic mechanisms are poorly studied. This work aimed to identify the adverse outcome pathways (AOPs) activated in the brain upon the use of a clinically relevant cumulative dose of MTX. Three-month-old male CD-1 mice were given a biweekly intraperitoneal administration of MTX over the course of three weeks until reaching a total cumulative dose of 6 mg/kg. Controls were given sterile saline in the same schedule. Two weeks after the last administration, the mice were euthanized and their brains removed. The left brain hemisphere was used for targeted profiling of the metabolism of glutathione and the right hemisphere for an untargeted metabolomics approach. The obtained results revealed that MTX treatment reduced the availability of cysteine (Cys), cysteinylglycine (CysGly), and reduced glutathione (GSH) suggesting that MTX disrupts glutathione metabolism. The untargeted approach revealed metabolic circuits of phosphatidylethanolamine, catecholamines, unsaturated fatty acids biosynthesis, and glycerolipids as relevant players in AOPs of MTX in our in vivo model. As far as we know, our study was the first to perform such a broad profiling study on pathways that could put patients given MTX at risk of cognitive deficits.

Oxalate (dys)Metabolism: Person-to-Person Variability, Kidney and Cardiometabolic Toxicity.

Oxalate is a metabolic end-product whose systemic concentrations are highly variable among individuals. Genetic (primary hyperoxaluria) and non-genetic (e.g., diet, microbiota, renal and metabolic disease) reasons underlie elevated plasma concentrations and tissue accumulation of oxalate, which is toxic to the body. A classic example is the triad of primary hyperoxaluria, nephrolithiasis, and kidney injury. Lessons learned from this example suggest further investigation of other putative factors associated with oxalate dysmetabolism, namely the identification of precursors (glyoxylate, aromatic amino acids, glyoxal and vitamin C), the regulation of the endogenous pathways that produce oxalate, or the microbiota's contribution to oxalate systemic availability. The association between secondary nephrolithiasis and cardiovascular and metabolic diseases (hypertension, type 2 diabetes, and obesity) inspired the authors to perform this comprehensive review about oxalate dysmetabolism and its relation to cardiometabolic toxicity. This perspective may offer something substantial that helps advance understanding of effective management and draws attention to the novel class of treatments available in clinical practice.