Not always a miracle - The case of the missing metastasis.

Spontaneous regression of malignant neoplasms is extremely rare, but renal cell carcinomas (RCC) are most often associated with this phenomenon. We report a case of a patient with personal history of RCC, who underwent nephrectomy and no other oncological treatment. One year after nephrectomy, a lung metastasis was detected and kept under follow-up for 3 years. Its size increased over time until a needle biopsy was performed, and its metastatic nature confirmed. Wedge resection of the lung nodule was performed, and no neoplastic cells were found, suggesting its spontaneous regression after biopsy. Different theories have been proposed to explain this phenomenon and, in most cases, the mechanism seems to involve the activation of the immune system. This case supports the importance of reducing tumor burden and the impact of the disturbance of the tumor microenvironment caused by instrumentation, in improving immune system activation and its essential role in neoplasm regression.

The Role of Platelet-Rich Plasma Injection for Muscle Strains in Athletes.

Muscle tears/strains are among the most common musculoskeletal injuries, posing a serious challenge for sports medicine. Aiming to reduce the time to return to play and the rate of reinjuries, apart from the traditional conservative treatments and rehabilitation protocols, new and innovative therapeutic options have emerged, particularly platelet-rich plasma (PRP). This study aims to present the available evidence regarding PRP injection for the treatment of muscle strains in athletes. Two databases were searched for articles published between January 2012 and December 2022 in Portuguese or English. The query used for the PubMed database was ("Muscles/injuries"[Mesh]) AND ("Athletes"[Mesh] OR "Athletic Injuries"[Mesh]) AND "Platelet-Rich Plasma"[Mesh], while for the Web of Science database the search was performed for "Platelet-rich plasma" AND "Muscle injuries" AND ("Athletes" OR "Athletic injuries"). Eleven studies involving athletes diagnosed with muscle injuries who received treatment with PRP injection alone, or in combination with traditional conservative treatment, compared to a control group, were included. Four randomized controlled trials, four systematic reviews/meta-analyses, two retrospective studies, and one comparative study were included. Current evidence from the highest-quality studies does not support the hypothesis of reduction of time to return to play and the rate of reinjuries after PRP injection, even though some studies reported positive results. However, the available evidence suggests that PRP might have a beneficial effect on the pain perceived by athletes following an acute muscle strain. It is challenging to arrive at definitive conclusions and translate these findings into a clinical context for treating muscle strains in athletes. The existing trials present several inconsistencies and limitations, with a heterogeneous set of patients and injuries, as well as the use of different and inconsistent methods for preparing, administering, and measuring the effects of PRP. To achieve consistent outcomes, standardizing PRP administration procedures is essential.

Health-Related Physical Fitness Evaluation in HIV-Diagnosed Children and Adolescents: A Scoping Review.

BACKGROUND: Health-related physical fitness has been widely used to investigate the adverse effects of HIV infection/ART in children and adolescents. However, methods/protocols and cut-points applied for investigating health-related physical fitness are not clear. The aim of this scoping review was to map the literature to identify gaps in knowledge regarding the methods/protocols and cut-points. METHODS: A scoping review, following the Joana Briggs Institute (JBI) guidelines, was conducted through ten major databases. Search followed the PCC strategy to construct block of terms related to population (children and adolescents), concept (health-related physical fitness components) and context (HIV infection). RESULTS: The search resulted in 7545 studies. After duplicate removal, titles and abstracts reading and full text assessment, 246 studies were included in the scoping review. Body composition was the most investigated component (n = 244), followed by muscular strength/endurance (n = 23), cardiorespiratory fitness (n = 15) and flexibility (n = 4). The World Health Organization growth curves, and nationals' surveys were the most reference values applied to classify body composition (n = 149), followed by internal cut-points (n = 30) and cut-points developed through small populations (n = 16). Cardiorespiratory fitness was classified through cut-points from three different assessment batteries, as well as cut-points developed through studies with small populations, muscular strength/endurance and flexibility were classified through the same cut-points from five different assessment batteries. CONCLUSIONS: The research on muscular strength/endurance, cardiorespiratory fitness and flexibility has been scarcely explored. The lack of studies that investigated method usability as well as reference values was evidenced.

Navigating complexity: The Supera's triumph in femoropopliteal lesions.

INTRODUCTION: The femoropopliteal sector endovascular treatment is particularly challenging due to its high tortuosity and torsional forces. Better results are still needed to ensure the long-term patency of stenting in this area. The Supera stent appears to change this paradigm. METHODS: This single-center retrospective cohort study aims to evaluate the efficacy and safety of femoropopliteal stenting with Supera in a real-world population. Seventy-nine patients were treated between January 2015 and December 2020, and the results are reported with a median follow-up of 28 months. RESULTS: Indications for revascularization were chronic limb-threatening ischemia with tissue loss (73.6%) or ischemic rest pain (17.7%) and claudication (7.6%). Thirty-six patients (45.6%) were classified as GLASS stage III according to the Global Limb Anatomic Staging System, with 65.8% and 30.4% in grades 3 and 4 of femoropopliteal and infrapopliteal sectors, respectively. The 36-month primary, primary-assisted, and secondary patency rates were 68.6%, 72.0%, and 79.0%, respectively, with an amputation-free survival rate of 86.6%. There was no significant difference between primary patency rates in GLASS stages I-II compared with GLASS stage III (36-month primary patency rates of 72% vs 63% respectively, p = 0.342) nor in amputation-free survival (88% vs 84%, p = 0.877). After adjusting for potential confounders, only the stent conformation significantly affected the primary patency rates, with a higher hazard of reintervention for the elongated (HR = 3.179; p = 0.36; CI 1.081-9.347) and the compressed (HR = 3.014; p = 0.42; CI 1.039-8.746) forms. CONCLUSIONS: The 36-month patency of the Supera stents in our real-world cohort was similar to other reported series. The GLASS stage did not interfere with the stent patency, proving it is a good choice even in the most adverse anatomy patients. Only the non-nominal stent conformation affected the primary patency rates in our patients.

Computational Framework to Model the Selective Laser Sintering Process.

Selective laser sintering (SLS) is one of the most well-regarded additive manufacturing (AM) sub-processes, whose popularity has been increasing among numerous critical and demanding industries due to its capabilities, mainly manufacturing parts with highly complex geometries and desirable mechanical properties, with potential to replace other, more expensive, conventional processes. However, due to its various underlying multi-physics phenomena, the intrinsic complexity of the SLS process often hampers its industrial implementation. Such limitation has motivated academic interest in obtaining better insights into the process to optimize it and attain the required standards. In that regard, the usual experimental optimization methods are time-consuming and expensive and can fail to provide the optimal configurations, leading researchers to resort to computational modeling to better understand the process. The main objective of the present work is to develop a computational model capable of simulating the SLS process for polymeric applications, within an open-source framework, at a particle-length scale to assess the main process parameters' impact. Following previous developments, virgin and used polymer granules with different viscosities are implemented to better represent the actual process feedstock. The results obtained agree with the available experimental data, leading to a powerful tool to study, in greater detail, the SLS process and its physical parameters and material properties, contributing to its optimization.

Defining the In Vivo Role of mTORC1 in Thyrocytes by Studying the TSC2 Conditional Knockout Mouse Model.

Background: The thyroid gland is susceptible to abnormal epithelial cell growth, often resulting in thyroid dysfunction. The serine-threonine protein kinase mechanistic target of rapamycin (mTOR) regulates cellular metabolism, proliferation, and growth through two different protein complexes, mTORC1 and mTORC2. The PI3K-Akt-mTORC1 pathway's overactivity is well associated with heightened aggressiveness in thyroid cancer, but recent studies indicate the involvement of mTORC2 as well. Methods: To elucidate mTORC1's role in thyrocytes, we developed a novel mouse model with mTORC1 gain of function in thyrocytes by deleting tuberous sclerosis complex 2 (TSC2), an intracellular inhibitor of mTORC1. Results: The resulting TPO-TSC2KO mice exhibited a 70-80% reduction in TSC2 levels, leading to a sixfold increase in mTORC1 activity. Thyroid glands of both male and female TPO-TSC2KO mice displayed rapid enlargement and continued growth throughout life, with larger follicles and increased colloid and epithelium areas. We observed elevated thyrocyte proliferation as indicated by Ki67 staining and elevated cyclin D3 expression in the TPO-TSC2KO mice. mTORC1 activation resulted in a progressive downregulation of key genes involved in thyroid hormone biosynthesis, including thyroglobulin (Tg), thyroid peroxidase (Tpo), and sodium-iodide symporter (Nis), while Tff1, Pax8, and Mct8 mRNA levels remained unaffected. NIS protein expression was also diminished in TPO-TSC2KO mice. Treatment with the mTORC1 inhibitor rapamycin prevented thyroid mass expansion and restored the gene expression alterations in TPO-TSC2KO mice. Although total thyroxine (T4), total triiodothyronine (T3), and TSH plasma levels were normal at 2 months of age, a slight decrease in T4 and an increase in TSH levels were observed at 6 and 12 months of age while T3 remained similar in TPO-TSC2KO compared with littermate control mice. Conclusions: Our thyrocyte-specific mouse model reveals that mTORC1 activation inhibits thyroid hormone (TH) biosynthesis, suppresses thyrocyte gene expression, and promotes growth and proliferation.

Cost-Effectiveness of Inpatient Continuous Glucose Monitoring.

Introduction Our department conducted a retrospective cohort study to compare the efficacy of continuous glucose monitoring devices versus capillary blood glucose in the glycemic control of inpatient type 2 diabetes on intensive insulin therapy in a Portuguese hospital. The use of continuous glucose monitoring devices was associated with improved glycemic control, including an increased number of glucose readings within target range and reduced hyperglycemic events, being safe concerning hypoglycemias. This is the cost-effectiveness analysis associated with these results. Aim The primary objective was to compare the cost-effectiveness of achieving glycemic control, defined as the number of patients within glycemic goals, between groups. Secondary endpoints included cost-effectiveness analyses of each time in range goal, and each percentual increment in time in range. Methods We defined each glycemic goal as: "readings within range (70-180 mg/dL) >70%", "readings below range (below 70 mg/dL) <4%", "severe hypoglycemia (below 54 mg/dL) <1%", "readings above range (above 180 mg/dL) <25%", "very high glycemic readings (above 250 mg/dL) <5%". Results Continuous glucose monitoring showed lower median cost per effect for the primary outcome (€11.1 vs. €34.9/patient), with lower cost for readings in range (€7.8 vs. €11.6/patient) and for both readings above range goals ("above 180mg/dL": €7.4 vs. €9.9/patient, and "above 250mg/dL": €6.9 vs. €17.4/patient). Conclusions There are no published data regarding the cost-effectiveness of continuous glucose monitoring devices in inpatient settings. Our results show that continuous glucose monitoring devices were associated with an improved glycemic control, at a lower cost, and endorse the feasibility of incorporating these devices into hospital settings, presenting a favorable cost-effective option compared to capillary blood glucose.

Diffuse hemispheric glioma with H3 p.K28M (K27M) mutation: Unusual non-midline presentation of diffuse midline glioma, H3 K27M-altered?

Diffuse midline glioma, H3 K27-altered (DMG-H3 K27) is an aggressive group of diffuse gliomas that predominantly occurs in pediatric patients, involves midline structures, and displays loss of H3 p.K28me3 (K27me3) expression by immunohistochemistry and characteristic genetic/epigenetic profile. Rare examples of a diffuse glioma with an H3 p.K28M (K27M) mutation and without involvement of the midline structures, so-called "diffuse hemispheric glioma with H3 p.K28M (K27M) mutation" (DHG-H3 K27), have been reported. Herein, we describe 2 additional cases of radiologically confirmed DHG-H3 K27 and summarize previously reported cases. We performed histological, immunohistochemical, molecular, and DNA methylation analysis and provided clinical follow-up in both cases. Overall, DHG-H3 K27 is an unusual group of diffuse gliomas that shows similar clinical, histopathological, genomic, and epigenetic features to DMG-H3 K27 as well as enrichment for activating alterations in MAPK pathway genes. These findings suggest that DHG-H3 K27 is closely related to DMG-H3 K27 and may represent an unusual presentation of DMG-H3 K27 without apparent midline involvement and with frequent MAPK pathway activation. Detailed reports of additional cases with clinical follow-up will be important to expand our understanding of this unusual group of diffuse gliomas and to better define the clinical outcome and how to classify DHG-H3 K27.

Physical Activity Questionnaire for Children: Validity and Cut-Points to Identify Sufficient Levels of Moderate- to Vigorous-Intensity Physical Activity Among Children and Adolescents Diagnosed With HIV.

PURPOSE: To investigate the validity of the Physical Activity Questionnaire for Older Children (PAQ-C) to assess the moderate- to vigorous-intensity physical activity (MVPA) level of children and adolescents diagnosed with HIV and propose cut-points, with accelerometer measures as the reference method. METHOD: Children and adolescents, aged 8-14 years (mean age = 12.21 y, SD = 2.09), diagnosed with HIV by vertical transmission, participated in the study. MVPA was investigated through the PAQ-C and triaxial accelerometer (ActiGraph GT3X+). Receiver operating characteristic curve and sensitivity and specificity values were used to identify a cut-point for PAQ-C to distinguish participants meeting MVPA guidelines. RESULTS: Fifty-six children and adolescents participated in the study. Among those, 16 met MVPA guidelines. The PAQ-C score was significantly related to accelerometry-derived MVPA (ρ = .506, P < .001). The PAQ-C score cut-point of 2.151 (sensitivity = 0.625, specificity = 0.875) was able to discriminate between those who met MVPA guidelines and those that did not (area under the curve = 0.751, 95% confidence interval, 0.616-0.886). CONCLUSION: The PAQ-C was useful to investigate MVPA among children and adolescents diagnosed with HIV and to identify those who meet MVPA guidelines.

Strong OLIG2 expression in supratentorial ependymoma, ZFTA fusion-positive: A potential diagnostic pitfall.

Ependymomas (EPN) are central nervous system neoplasms that exhibit an ependymal phenotype. In particular, supratentorial EPN (ST-EPN) must be differentiated from more aggressive entities such as glioblastoma, IDH-wildtype. This task is frequently addressed with the use of immunohistochemistry coupled with clinical presentation and morphological features. Here we describe the case of a young adult presenting with migraine-like symptoms and a temporoinsular-based expansile mass that was first diagnosed as a GBM, mostly based on strong and diffuse oligodendrocyte transcription factor 2 (OLIG2) expression. Molecular characterization revealed a ZFTA::RELA fusion, supporting the diagnosis of ST-EPN, ZFTA fusion-positive. OLIG2 expression is rarely reported in tumors other than GBM and oligodendrocyte-lineage committed neoplasms. The patient was treated with radiotherapy and temozolomide after surgery and was alive and well at follow-up. This report illustrates the need to assess immunostains within a broader clinical, morphological and molecular context to avoid premature exclusion of important differential diagnoses.

Uterine Sarcoma With EML4::NTRK3 Fusion: A Spectrum of Mesenchymal Neoplasms Harboring Actionable Gene Fusions.

NTRK gene fusions are part of a paradigm shift in oncology, arising as one of the main genomic alterations with actionability in the so-called "agnostic setting." In gynecologic pathology, the recent description of uterine sarcoma resembling fibrosarcoma and with NTRK rearrangements ( NTRK -rearranged uterine sarcoma) highlights the importance of recognizing clinicopathological cues that can lead to genomic profiling. Herein, we report the case of a 43-year-old woman presenting with vaginal bleeding and pelvic mass. Histopathology of the tumor showed moderately atypical spindle cells arranged in long fascicles reminiscent of fibrosarcoma, along with immunohistochemical positivity for S100, CD34, and pan-tropomyosin receptor kinase. This prompted RNA-sequencing and the finding of a rare EML4::NTRK3 fusion. Clinical, histologic, and molecular findings are described, in addition to discussions regarding differential diagnoses and possible implications of the findings in clinical practice.

Schistosomiasis: A neglected cause of pulmonary arterial hypertension in Brazil.

Schistosomiasis is a prevalent disease in Brazil whose etiological agent is Schistosoma mansoni, the main species associated with pulmonary arterial hypertension (PAH), a serious complication. It is estimated that this complication affects up to 15% of patients with the hepatosplenic form of the disease. Despite being an endemic country, Brazil does not have a screening scheme for cases of PAH associated with schistosomiasis (PAH-Sch), nor protocols for notification and treatment of this vascular complication. The objectives of this literature review are to gather knowledge about the pathophysiology, clinical manifestations, diagnosis and treatment of PAH-Sch and to highlight relevant aspects for the Brazilian reality. The pathophysiology, although lacking information, has proliferative vasculopathy as a central element. The clinical presentation of this disease can be asymptomatic or with nonspecific manifestations. Thus, complementary exams are essential for a confirmatory diagnosis, the gold standard being right heart catheterization, a scarce resource in endemic regions of the country. The treatment of PAH-Sch is similar to that performed for other causes of PAH, but the impact of anthelmintic therapy on the evolution of the vascular pathology is unknown. Therefore, Brazil needs to develop a screening plan for early diagnosis of PAH-Sch and new studies should be carried out to determine a more specific treatment.

Advances in Aquaculture Hatchery Techniques of Sea Urchin Sphaerechinus granularis (Lamarck, 1816) (Echinoidea: Toxopneustidae): Broodstock Conditioning and Spawning Induction.

In response to the growing demand for sea urchin gonads (roe or uni) in Asian and European markets and the concerns regarding the overexploitation of wild populations, this preliminary study addresses the need for cost-effective protocols in echinoculture. The primary focus of this research was to evaluate the gonadosomatic index (GI) in captive-conditioned Sphaerechinus granularis over a five-month period and compare it with that of their wild-caught conspecifics. Additionally, two different spawning induction methods were assessed: potassium chloride (KCl) injection and agitation. Results indicate that captive-conditioned sea urchins exhibit significantly higher GI values when compared to their wild-caught counterparts. Furthermore, it was observed that the agitation method is equally effective as the KCl injection in triggering a positive response, i.e., gamete ejection, while maintaining lower mortality rates among the subjected S. granularis. In conclusion, this preliminary study underscores the pivotal role of broodstock conditioning in supporting the sustainability of sea urchin aquaculture. Moreover, the spawning induction method through agitation emerges as a viable alternative to the traditional intracelomic KCl injection, offering comparable efficacy without compromising the survival of the broodstock. These findings have significant implications for the development of sustainable sea urchin farming practices.

Prevalence and Risk Factors of Leptospira spp. Infection in Backyard Pigs in the State of Paraná, Brazil.

Leptospirosis is a zoonotic disease that poses a significant threat to human and animal health worldwide. Among different animal species, pigs are known to play a crucial role in the transmission of the pathogenic Leptospira spp. This study aimed to investigate the prevalence of Leptospira spp. infection and associated risk factors in backyard pigs in the state of Paraná, Brazil. A set of 1393 blood samples were collected from pigs on 188 subsistence properties from 136 different municipalities of the Paraná state and tested using the microscopic agglutination test (MAT) to detect antibodies against 24 different Leptospira spp. serovars. The results revealed an overall seroprevalence of 15.87% (221/1393; 95% CI: 13.95-17.78%) for Leptospira spp. antibodies, with Icterohaemorrhagiae, Butembo, and Pomona being the most commonly detected in serovar levels. The lack of rodent control (OR 1.12, 95% CI: 0.63-1.98, p = 0.02) was the only variable associated with disease incidence and was identified as a significant risk factor for Leptospira spp. infection in this context. These findings highlight the urgent need to implement effective control measures, such as improved housing conditions, rodent control, and veterinary assistance, to prevent the spread of this zoonotic disease in backyard pigs in Paraná, Brazil.

Continuous Glucose Monitoring vs. Capillary Blood Glucose in Hospitalized Type 2 Diabetes Patients.

INTRODUCTION: The emergence of continuous glucose monitoring devices revolutionized the monitoring of diabetes, allowing real-time measurement of interstitial glucose levels. These devices are especially important for people with diabetes treated with insulin therapy and have been extensively studied in outpatient settings. In hospitalized patients, studies using continuous glucose monitoring have focused mainly on evaluating its accuracy and feasibility, but the results were unclear on whether continuous glucose monitoring was superior to capillary blood glucose in improving glycemic control and further research is needed to support the use of these devices in hospitalized patients with diabetes. OBJECTIVE: The primary endpoint of this study was to assess the increase in time-in-range (glycemic readings between 100-180 mg/dL) in hospitalized patients with continuous glucose monitoring, compared to capillary blood glucose. The secondary endpoints included the assessment of reductions in hypoglycemia incidence, mean glucose levels, and glucose coefficient of variation. Additionally, we assessed the intervention's impact on reducing the length of hospital stay, mortality rates, and incidence of inpatient infections. RESEARCH DESIGN AND METHODS: This was a retrospective, cohort study of 60 hospitalized patients with type 2 diabetes, divided into two groups of 30 individuals each: an intervention group monitored through continuous glucose monitoring and a control group using capillary blood glucose. RESULTS: Both groups were comparable in terms of demographic and clinical characteristics. Continuous glucose monitoring users had a higher number of readings per day (six vs. four, p < 0.001), in-range readings (53.5% vs. 35%, p = 0.027), fewer above-range readings (25.5% vs. 56.5%, p = 0.003), particularly above 250 mg/dL (5% vs. 27.5%, p = 0.001), with no difference in the percentage of hypoglycemia occurence (1% vs. 0%, p = 0.107). Lower mean glucose (161.9 mg/dL vs. 206.5 mg/dL, p < 0.001) was also observed in this group. No difference was observed in mortality, length of stay, or in infection rate (p = 1.000, p = 0.455, and p = 0.606, respectively). CONCLUSIONS: This retrospective study supports the use of continuous glucose monitoring in optimizing glycemic control in hospitalized patients with type 2 diabetes on intensive insulin therapy. These findings suggest that continuous glucose monitoring can improve time-in-range and prevent hyperglycemia.

Ascending aortobifemoral and adjunct carotid bypass grafts.

We describe a case of simultaneous ascending aortobifemoral and right common carotid artery bypass to treat a symptomatic brachiocephalic artery and juxtarenal chronic total occlusion in a 68-year-old female patient with unfavorable characteristics for endovascular and standard aortofemoral procedures. Mid-term follow-up revealed sustained remission of symptoms, quality of life quality of life improvement, and patent bypass grafts. In highly selected patients, this solution can be useful when treating other intrathoracic diseases, as well as allowing the simultaneous revascularization of two remote arterial beds.

Digitisation of patient preferences in palliative care: mobile app prototype.

BACKGROUND: Engaging in advance care planning can be emotionally challenging, but gamification and technology are suggested as a potential solution. OBJECTIVE: Present the development stages of a mobile app prototype to improve quality of life for patients in palliative care. DESIGN: The study started with a comprehensive literature review to establish a foundation. Subsequently, interviews were conducted to validate the proposed features of the mobile application. Following the development phase, usability tests were conducted to evaluate the overall usability of the mobile application. Furthermore, an oral questionnaire was administered to understand user satisfaction about the implemented features. RESULTS: A three-phase testing approach was employed based on the chosen user-centred design methodology to obtain the results. Three iterations were conducted, with improvements being made based on feedback and tested in subsequent phases. Despite the added complexity arising from the health status of patients in palliative care, the usability tests and implemented features received positive feedback from both patients and healthcare providers. CONCLUSION: The research findings have demonstrated the potential of digitisation in enhancing the quality of life for patients in palliative care. This was achieved through the implementation of patient-centred design, personalised care, the inclusion of social chatrooms and facilitating end-of-life discussions.

2023 UPDATE: Luso-Brazilian evidence-based guideline for the management of antidiabetic therapy in type 2 diabetes.

BACKGROUND: The management of antidiabetic therapy in people with type 2 diabetes (T2D) has evolved beyond glycemic control. In this context, Brazil and Portugal defined a joint panel of four leading diabetes societies to update the guideline published in 2020. METHODS: The panelists searched MEDLINE (via PubMed) for the best evidence from clinical studies on treating T2D and its cardiorenal complications. The panel searched for evidence on antidiabetic therapy in people with T2D without cardiorenal disease and in patients with T2D and atherosclerotic cardiovascular disease (ASCVD), heart failure (HF), or diabetic kidney disease (DKD). The degree of recommendation and the level of evidence were determined using predefined criteria. RESULTS AND CONCLUSIONS: All people with T2D need to have their cardiovascular (CV) risk status stratified and HbA1c, BMI, and eGFR assessed before defining therapy. An HbA1c target of less than 7% is adequate for most adults, and a more flexible target (up to 8%) should be considered in frail older people. Non-pharmacological approaches are recommended during all phases of treatment. In treatment naïve T2D individuals without cardiorenal complications, metformin is the agent of choice when HbA1c is 7.5% or below. When HbA1c is above 7.5% to 9%, starting with dual therapy is recommended, and triple therapy may be considered. When HbA1c is above 9%, starting with dual therapyt is recommended, and triple therapy should be considered. Antidiabetic drugs with proven CV benefit (AD1) are recommended to reduce CV events if the patient is at high or very high CV risk, and antidiabetic agents with proven efficacy in weight reduction should be considered when obesity is present. If HbA1c remains above target, intensification is recommended with triple, quadruple therapy, or even insulin-based therapy. In people with T2D and established ASCVD, AD1 agents (SGLT2 inhibitors or GLP-1 RA with proven CV benefit) are initially recommended to reduce CV outcomes, and metformin or a second AD1 may be necessary to improve glycemic control if HbA1c is above the target. In T2D with HF, SGLT2 inhibitors are recommended to reduce HF hospitalizations and mortality and to improve HbA1c. In patients with DKD, SGLT2 inhibitors in combination with metformin are recommended when eGFR is above 30 mL/min/1.73 m2. SGLT2 inhibitors can be continued until end-stage kidney disease.

Raptor levels are critical for ß-cell adaptation to a high-fat diet in male mice.

OBJECTIVE: The essential role of raptor/mTORC1 signaling in ß-cell survival and insulin processing has been recently demonstrated using raptor knock-out models. Our aim was to evaluate the role of mTORC1 function in adaptation of ß-cells to insulin resistant state. METHOD: Here, we use mice with heterozygous deletion of raptor in ß-cells (ßraHet) to assess whether reduced mTORC1 function is critical for ß-cell function in normal conditions or during ß-cell adaptation to high-fat diet (HFD). RESULTS: Deletion of a raptor allele in ß-cells showed no differences at the metabolic level, islets morphology, or ß-cell function in mice fed regular chow. Surprisingly, deletion of only one allele of raptor increases apoptosis without altering proliferation rate and is sufficient to impair insulin secretion when fed a HFD. This is accompanied by reduced levels of critical ß-cell genes like Ins1, MafA, Ucn3, Glut2, Glp1r, and specially PDX1 suggesting an improper ß-cell adaptation to HFD. CONCLUSION: This study identifies that raptor levels play a key role in maintaining PDX1 levels and ß-cell function during the adaptation of ß-cell to HFD. Finally, we identified that Raptor levels regulate PDX1 levels and ß-cell function during ß-cell adaptation to HFD by reduction of the mTORC1-mediated negative feedback and activation of the AKT/FOXA2/PDX1 axis. We suggest that Raptor levels are critical to maintaining PDX1 levels and ß-cell function in conditions of insulin resistance in male mice.

Challenges in Management of Concomitant Primary Aldosteronism and Pheochromocytoma.

BACKGROUND Primary aldosteronism and pheochromocytoma are endocrine causes of secondary arterial hypertension. The association of primary aldosteronism and pheochromocytoma is rare and the involved mechanisms are poorly understood. Either there is a coexistence of both diseases or the pheochromocytoma stimulates the production of aldosterone. Since management approaches may differ significantly, it is important to properly diagnose the 2 conditions. We describe concomitant pheochromocytoma and primary aldosteronism in a patient with resistant hypertension, which demanded a challenging and individualized approach. CASE REPORT A 64-year-old man was sent for observation in our department for type 2 diabetes and resistant hypertension. Laboratory work-up suggested a primary aldosteronism and a pheochromocytoma. The abdominal CT (before and after intravenous contrast, with portal and delayed phase acquisitions) revealed an indeterminate right adrenal lesion and 3 nodules in the left adrenal gland: 1 indeterminate and 2 compatible with adenomas. A 18F-FDOPA PET-CT showed increased uptake in the right adrenal gland. The patient underwent a right adrenalectomy and a pheochromocytoma was confirmed. An improvement in glycemic control was observed after surgery but the patient remained hypertensive. A captopril test confirmed the persistence of primary aldosteronism, and he was started on eplerenone, achieving blood pressure control. CONCLUSIONS This case highlights the challenges in diagnosing and treating the simultaneous occurrence of pheochromocytoma and primary aldosteronism. Our main goal was surgical removal of the pheochromocytoma due to the risk of an adrenergic crisis.